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Background Treatment adherence in patients with psychotic disorders is an important challenge for physicians and caregivers, and various methods have been suggested in order to improve this parameter. Therapeutic adherence is defined as the extent to which the patient's behavior corresponds to the agreement between him or her and the prescribing physician. Monitoring this parameter is essential, because of its implications for the patient's prognosis, evolution, risk of relapse, quality of life, and overall functioning. A large number of factors have been associated with the ability to influence therapeutic adherence, e.g. frequency of administration and number of daily medications, adverse events related to antipsychotics, lack of insight or partial insight. Finding new ways to improve therapeutic adherence may be of considerable help for clinicians and may improve patients' functional prognosis. Methods Main electronic databases (PubMed, CINAHL, PsychInfo, Cochrane, EMBASE, Thomson Reuters/Web of Science) were searched using as keywords "therapeutic adherence", "treatment adherence", combined with "schizophrenia", "schizoaffective disorder", and "psychotic disorders". All papers published between 1988 and 2018 were included in the review. RCTs, as well as meta-analyses, systematic reviews and narrative reviews, case reports, case series, and letters to the editor were included. Papers without specified diagnoses of psychotic disorders, which included poorly specified interventions, or which included patients under 18 years old were excluded from this review. Results A number of 288 papers were found after the primary search, and 41 remained after filtering out the rest of studies based on inclusion and exclusion criteria. Adherence therapy based on motivational interview, and psycho-educational approaches were the most reported psychological interventions. Adherence therapy was associated with lower duration of re-hospitalization, improvements in severity of the main symptoms, and better functioning. Good-quality data about the efficacy of nursing techniques for improving therapeutic adherence are not available. Assertive community treatment is useful in patients with schizophrenia, because it improved the general psychopathology, functioning, quality of life, and decreased the re-hospitalization rates. Long-acting injectable atypical antipsychotics were also evaluated for patients with low adherence and this formulation decreased the number of re-hospitalization and treatment discontinuation rate. Aripiprazole tablets with sensor represent the newest addition in the clinician's toolkit for improving therapeutic adherence, but data derived from independent trials about the effects of this formulation over patients' rate of re-hospitalization and antipsychotic discontinuation rate are still lacking. Discussion Psychological and pharmacological interventions focused on treatment adherence augmentation have impact over patients' functionality, several aspects of the general psychopathology, re-hospitalization and treatment discontinuation rates. Data about superiority of one therapeutic adherence- focused intervention over another are not available, so the decision about what method should be used depends mostly on the clinician's judgment. [ABSTRACT FROM AUTHOR]

Background: Behavioural findings suggest that the emotion processing abnormalities typically observed in established schizophrenia are already present in patients with a first episode of psychosis (FEP). Evidence has been less consistent in people at clinical high risk for psychosis (CHRp). While several studies have reported unaltered behavioural performance on emotion identification in people at CHRp compared to healthy controls, some studies have shown poorer negative emotion recognition. A growing number of functional magnetic resonance (fMRI) studies have investigated brain response to emotion processing to elucidate the mechanisms underlying these processes in FEP patients and CHRp individuals. Despite the marked expansion of this field over the last two decades, to date, no systematic review or meta-analysis has attempted to synthesise the evidence on the neural bases of emotion processing in these groups as potential markers of psychosis vulnerability and expression. Methods: The PubMed and Ovid MEDLINE databases were searched for published English-language articles applying an emotion processing task during fMRI in a FEP and/or a CHRp sample compared to healthy controls. References of included papers were also screened. For CHRp studies, only those including participants by the basic or attenuated symptom presentation criteria were included. Individual study methodology and results were extracted and systematically reviewed. In addition, at present, statistical parametric mapping contrast maps (‘T-maps’) are being collected from study authors and will be meta-analysed using the Seed-based d Mapping method. The contrasts meta-analysed will be the ones most commonly reported in the studies identified, i.e., of all emotion over comparison conditions and of negative emotion over neutral conditions. These will be meta-analysed separately, as behavioural evidence suggests that emotion recognition performance in these populations might be valence specific. Results: For the systematic review, 4,389 papers were identified through the search. 19 relevant fMRI papers were identified and their references were screened. 17 articles were included after full-text screening. Six out of twelve fMRI studies in the FEP population reported lower brain activation to emotion processing tasks compared to healthy controls. Four articles reported region-specific hyper- and hypoactivations and two studies found no significant difference. Of the seven studies in the CHRp population, one study reported lower brain response to emotion relative to healthy controls, two studies found hyperactivations, one study found region-specific increases and decreases, and two studies reported no significant difference. The most consistent finding across studies was lower amygdala activation in FEP participants (n=6). Conversely, in the CHRp population one article found an increase in amygdala response to emotion with age, consistently with one other article but contrasting with another study showing activity decreases in this region. Discussion: To our knowledge, no previous systematic review or metaanalysis has synthesised the fMRI findings of emotion processing in both people at CHRp and a FEP. The present systematic review shows that while more consistent hypoactivations are found in the FEP population, results are less consistent in CHRp studies. The undergoing meta-analysis will quantitatively synthesise these findings. Elucidating the nature of emotion processing aberrances in early psychosis may help understand the functional changes across both vulnerability and symptom emergence phases and inform molecular investigations into its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairments are a core feature of schizophrenia. Although cognitive impairments have consistently shown to have negative impacts on functional outcomes among individuals with schizophrenia, assessing and treating these symptoms in clinical settings remains a difficult challenge. Interestingly, the growing potential of new digital technologies, such as smartphone applications and virtual reality, hold great promise in alleviating these impairments. Methods: This presentation will introduce results from two recent studies using digital technologies to assess and treat cognitive symptoms in schizophrenia. In the first study, smartphone versions of the pen-and-paper Trail Making Tests A and B were developed. These cognitive tests measure speed of processing and cognitive flexibility. We assessed the validity of the smartphone versions of both Trail Making Tests in measuring these cognitive domains in in 37 healthy controls and 26 individuals with schizophrenia. Following the initial assessment, participants were asked to complete the two smartphone cognitive tests once a week for three months. This served as a measure of cognitive performance over time Results: Results showed that it was feasible to measure cognition using a smartphone application in schizophrenia. Performances on both smartphone cognitive tests were significantly and positively correlated with the pen-and-paper versions (Parts A: r = 0.65, p < .001; Parts B: r= 0.44, p= .01). Additionally, significant differences were observed between controls and individuals with schizophrenia on both smartphone tests (Part A: t = -3.88, p = .004; Part B: t = -3.29, p = .002). Moreover, longitudinal results showed no significant effect of practice over time on the smartphone cognitive tests. Discussion: Digital technologies have the potential to optimize cognitive assessments, monitoring, and care in schizophrenia. Our findings support the feasibility and efficacy of using digital technologies to measure and treat cognitive impairments in schizophrenia. Our research also highlights the importance of including scientists, clinicians, and content experts with schizophrenia in the development of these tools to ensure their validity and facilitate clinical implementation. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic (AP) medication is associated with metabolic dysregulation, increasing the risk for weight gain. Previously, we showed that all antipsychotics are related with body weight gain and there was a time effect, the longer the AP was taken the more the weight gain was (Bak, Fransen, Janssen, van Os, & Drukker, 2014). This study included data from 1999–2013. The aim of this study is to up-date the previous study on weight gain by extending the search from 1960 – July 2019. So, older studies of before 2000 were in included as well as studies on AP’s after 2014. The differences in weight change between the various AP’s were calculated. Methods: A systematic search was performed using the databases PubMed and EMBASE. Eligible RCTs were identified and no restriction was made regarding diagnosis or publication date. Statistical analysis was based on a random effects model from which forest plots were generated. Effect sizes were reported as the standardized mean difference (SMD) with 95% confidence intervals (CI). Results were presented stratified by four exposure categories, namely < 6 weeks, 6–16 weeks, 16–38 weeks, and ≥ 38 weeks. Furthermore, that results are divided in AP naive patients (patients who had no AP previously) and patient in whom AP were switched from at least one other AP. Patients >17 years of age were excluded and all diagnostic categories were included. Results: In total 3488 papers were found. Following PRSIMA guidelines in total 472 papers were eligible for inclusion. Preliminary results. For the longer term 16–38 & >38 wks all AP-naive patients showed an increase in weight of > 5 kg, except for aripiprazole (< 6wks, 0.46kg; 6-16wks, 2.04kg; 16-38wks, 4.5kg; >38 wks, 3.31kg), paliperidone (< 6wks, 1.24kg; 6-16wks, 1.69kg; 16-38wks, -0.3kg; >38wks 0.2kg), quetiapine (< 6wks, 2.51kg; 6-16wks, 2.69kg; 16-38wks, 3.02kg; >38wks 6.14kg) and ziprasidone (< 6wks, 0.06kg; 6-16wks, 0.32kg; 16-38wks, 0.51kg; >38wks 2.18kg). The result of the switch studies shows that clozapine and olanzapine result in most weight gain after switch. Other AP result in modest weight gain to weight loss over the various time periods: amisulpride (range -0.76 and 1.40), aripriprazole (range -0.81 and 0.81), asenapine (-0.99 – 1.14), haloperidol (0.49 – 1.31) and ziprasidone (-1.18 – -0.38). During SIRS final results will be presented. Discussion: The number of studies in AP naif patients is limited. Most RCT’s discuses medication evaluation after switch into a new compound. Here, metabolic changes may interact with evaluation of changes in weight. However, switching an AP because after severe weight gain needs to be considered with caution as it does not result in considerable weight loss. The AP-naive show that all AP lead to weight gain. Given only patient older than 17years were included, this might explain the limited number of available studies. However, younger age seems to be associated were an increased risk of weight gain. [ABSTRACT FROM AUTHOR]

Background: Despite the progress in treatment and clinical outcomes, schizophrenia remains a highly stigmatized disease and imposes a challenge to families and patients towards recovery. Stigma can debilitate individuals as much as the disease itself, representing one of the most relevant obstacles to overcome the illness: it hinders the pursuit of autonomy and achievement of life goals. Stigma is complex and multilayered and its research usually focus on patients and society, but a lower number of studies address health professionals stigma. Even fewer investigate stigma of researchers. Thus, our objective is to analyze how the most cited research papers published in 2018 addressing schizophrenia depict the disease to identify putative stigma among researchers. Methods: In this exploratory study, we conducted a search using Web of Science (WoS) with the following terms: (“patients with schizophrenia”) OR (“schizophrenia patients”). We restricted the search to articles published in 2018 and selected the 20 studies with the highest total number of citations. We identified how the authors defined schizophrenia and then categorized the definition in three groups: (1) negative perspective, in which depreciative words were used to define the disease; (2) neutral definition, in which emphasis is given to the description of epidemiological data; and (3) neutral to positive definition, when negative outcomes were listed as possibilities, not certainties. Two independent authors (G.K. and M.M.) categorized each article and eventual conflicts were solved by a third author (A.G.) Results: 25% of the studies depicted a clearly negative perspective of schizophrenia. In these studies, the disease was described with words such as “devastating” and “highly disabling”. Most studies (60%) were coded as neutral, being mainly descriptive of current epidemiological data. Only 3 studies (15%) were identified as more favorable, since they acknowledged the possibility of better outcomes among patients with schizophrenia. Discussion: In the current schizophrenia scientific literature, negative views of the disease are still largely common. Considering the role of highly cited papers as opinion formers, we suggest that as occurred in other fields, such as the change in address of suicide by the media, some orientation should be adopted to avoid further contributions to the schizophrenia stigma. [ABSTRACT FROM AUTHOR]

Background: Sexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. The aim of this systematic review was to synthesize and analyze the evidence on the management of antipsychoticrelated sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporated Methods: EMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline. Results: The primary outcome measure was any change in sexual function. Results 6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction. Discussion: Due to the lack of high-quality data, no clinical recommendations can be made. Our findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Background Long-acting injectable antipsychotics (LAIs) are recommended to decrease relapse in SZ and their relevance is acknowledged in every treatment guideline available internationally. Yet their rate of use is reported to be very low (6%) in Canada, based on a paper by Williams et al. It could be hypothesized that the fact that second generation LAIs (SGA-LAIs) had just become available might have accounted for these modest rates of use, given the strong inclination of clinicians to prefer prescribing SGAs, that had been previously available only in an oral form. However, this paper dates were published in 2006, and we are unaware from any other data on possible changes in LAI used that could have occurred following the increasing availability of new second-generation LAIs or after the publication of Québec and Canada recommendations of experts. The present report examines the changes in rates of LAIs in Québec from 2003 until 2017. Methods We obtained from the number of LAIs prescriptions reimbursed for each month from 2003 to 2017 by the provincial public insurance system that provides coverage to more than 90% of people suffering from a psychotic disorder. As this data set was obtained from a commercial entity (IMS), it did not include any information on the individuals receiving this LAIs. Hence, we computed their rate of use per 1000,000 people, taking into account the increase in Québec population over that period. In the absence of any diagnostic information, change in number of prescription might reflect changes in their use in diagnostic categories other that SZ and related psychotic disorder. To address this, we performed sensitivity analyses that will be detailed below. Results Over the studied period, the rate of use of LAIs more than tripled, going from 32,4/100 000 in 2003 to 99,6 per 100 000 in 2016. The use of first-generation LAIs decreased from 33,6 per 100 000 in 2003 to 24,5 per 100 000 in 2017. The use of second-generation LAIs (SGA-LAIs), first introduced in 2003 (Risperidone-Consta), reached 75,1/100,000 in 2017. Further analyses of changes in rates of use started in 2004, a few months after the introduction of the first SGA-LAI and increased in a linear pattern over the period of the study, without any significant inflection point over that period. Discussion These data show that LAI use in Québec has increased steadily since 2004, and that this use seems to coincide with the introduction of the first SGA-LAI, without further increase co-occurring with the publication and dissemination of expert recommendations. This supports the hypothesis that the modest rates of use of LAIs that was previously reported in Québec and Canada might have resulted from the fact that only FGA were available in the LAI form while SGAs had become the mainstay in pharmacological treatment of psychotic disorders. However, the lack of diagnostic information on the persons who have used these LAIs prevent concluding about their current rates of use in people suffering from SZ and related psychotic disorders as well as on the variations of these rates over the study period. To address these limitations, we are currently planning further analyses based on the public health care system that will combine information of medication use and diagnostic information on the people with whom these medications are used. [ABSTRACT FROM AUTHOR]

Background: Smartphone technology has seen expanding interest across nearly all areas of medicine, including psychiatry, where app-based technologies frequently function as proxies for digitized behavioural phenotypes (Firth and Torous 2015). In the area first episode psychosis especially, there has been a rising interest in the use of digital platforms for patient self-management as well as for assessment of symptom domains (Ben-Zeev et al. 2014; Bell et al. 2018). Methods: This paper discusses findings from a 3 year-long ethnographic study carried out within a first episode psychosis program in Toronto, Canada, in combination with a discourse analysis of the clinical and research literature relating to the use of self-monitoring technologies within first episode psychosis contexts. The qualitative data consists of formal and informal interviews with psychiatric service users, family members, and clinicians (n=45 interviews), in addition to observational field work within the clinical setting. Data were analyzed thematically within an interpretivist-constructivist frame, and triangulated through reflexive field notes, member-checking, and the authors’ clinical experience within the field. Themes were reviewed with senior clinicians in the first episode clinic setting as well as psychiatric service users for reliability and fidelity. Results: Self-monitoring technologies are increasingly used in both research and clinical care settings, most frequently related to the management of medication side effects and the tracking of the phenomenological aspects of psychotic and psychotic-like experiences. The uptake of these technologies by psychiatric service users in this setting was varied: at times, symptom and side effect tracking faciliated conversations about uncomfortable topics such as sexual side effects of antipsychotics, while in other instances the use of self-monitoring technologies was intrusive. Challenges with self-monitoring were likely to arise when issues relevant to understanding complex phenomena such as medication adherence were prematurely narrowed or when experiential narratives were foreclosed by the structure imposed by the technologies themselves. Resistance to self-monitoring arose in novel and interesting ways. Discussion: Engaging in self-monitoring, whether for side effect tracking or phenomenological analysis of moment-to-moment experiences have significant material effects on those engaged in such practices. When we consider the study findings through the lens of contemporary mental health ethics, we can appreciate how such technologies carry with them a potential for what has been termed “epistemic injustice” (Medina 2013; Fricker 2007), even at the same time as they offer potentially novel, meaningful forms of health care engagement. Grappling with this tension is of critical importance in light of the expansion of such platforms in both clinical and research environments. [ABSTRACT FROM AUTHOR]

Background: Theory of mind (ToM) is a core feature of the social functioning because it influences the way an individual perceive other people’s mental states, and because responses to social cues are shaped by one’s ToM. Patients diagnosed with schizophrenia spectrum disorders (SSD) often present cognitive symptoms as part of their clinical manifestations, and there is a controversy about the relation of ToM deficiencies and more general cognitive features of schizophrenia and related disorders [1]. In order to find data that may clarify if ToM deficiencies are part of the schizophrenia cognitive dimension, or if they precede the onset of psychosis and simply coexist with other symptoms met in this type of disorders, a literature analysis was conducted. Methods: This review included papers published between January 2000 and August 2019 in the main electronic databases (PubMed, Cochrane, EMBASE, CINAHL). Keywords used for database search were “schizophrenia spectrum disorders”, “schizophrenia”, “schizoaffective disorder”, “delusional disorder”, or “schizophreniform disorder” and “theory of mind”. There was included no age limit, and no exclusion criteria referred to the duration of the disorder. Results: A number of 93 papers resulted after the primary search, but only 17 remained after de-duplication and application of inclusion/exclusion criteria. A study with young adults diagnosed with first episode of schizophrenia and matched controls (n=128) suggested that ToM deficits are partly independent of other cognitive functions [1]. Another study (n=1630 children 11–12 years old) reported specific alterations in ToM may be associated with specific types of psychotic experiences, and exaggerated type of ToM may index risk for developing psychosis and paranoid delusions in particular [2]. Adolescents who were genetically at high risk for schizophrenia had social skills impairments but no ToM deficits in a study [3]. Also, there is evidence for ToM deficits in the healthy relatives of schizophrenics, patients with delusional disorder, and individual with high schizotypy scores [4]. The hyper-connectivity in SSD has been confirmed on functional magnetic resonance imaging and default connectivity is correlated to and predictive of theory of mind performance [5]. A significant number of papers (n=10) did not formulate any clear argument to support the independent versus secondary status of the ToM deficits in relation to the SSD cognitive dimension. Discussion: ToM deficiencies are important elements that have been associated with the social skills and functioning in patients with SSD, although it is not clear if these elements exist independently from other cognitive symptoms. Relatives of patients with SSD may present ToM deficits, and data exist about the correlation between ToM abnormalities and several positive symptoms of the SSD. However, more well designed trials are needed in order to confirm the association between ToM impairments and SSD. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant schizophrenias include a heterogeneous group of patients with significant individual and societal consequences, and a high number of these patients fail to respond to clozapine (almost 50%). Patients who did not respond to the second line antipsychotics are a challenge for their treating physicians and although many augmentation strategies have been tried, including other agents with antipsychotic properties, mood-stabilizers, antidepressants, glutamatergic agents and neuromodulation techniques. Methods: A literature review was conducted in the main electronic databases (PubMed, Cochrane, EMBASE, CINAHL), and papers published between January 2000 and August 2019 were included. The search paradigm was “ultra-resistant schizophrenia” or “clozapine-resistant schizophrenia” or “add-on to schizophrenia” and non-proprietary names of currently marketed antipsychotics, mood stabilizers, antipsychotics, nootropics, “neuromodulation techniques” and “psychotherapy”. Results: A number of 197 papers resulted from the primary search, and 45 papers remained after de-duplication and application of inclusion and exclusion criteria. Electroconvulsive therapy seems to be efficient and the response rate ranges from 37.5 to 100% in cases of ultra-resistant schizophrenia [1]. Transcranial direct-current stimulation (tDCS) lead to meaningful improvement in positive symptoms and overall symptomatology when compared to no standard treatment of the control group, in a 4 weeks trial [2]. A 21-week pragmatic trial did not find any significant lasting effect of the cognitive-behavioral therapy (CBT) on total symptoms of schizophrenia compared to treatment as usual, although improvements were detected [3]. Pharmacological augmentation of clozapine included amisulpride (results were not significant), memantine (positive effects, but the trial included a small number of patients), reboxetine (uncertain efficacy), ziprasidone (possible effective on negative and cognitive symptoms), aripiprazole (uncertain effect based on multiple trials), lamotrigine (not efficient), pimozide (not efficient), sertindole (no benefits detected, possible worsen psychosis in several cases), tetrabenazine (not effective), duloxetine (possible efficacy on negative and general psychopathology, but not on the executive cognitive functions), topiramate (no efficacy), valproic acid (possible efficacy, larger trials needed), risperidone (not efficient), donepezil (not efficient), mirtazapine (possible efficacy), sulpiride (possible efficacy in a subgroup of schizophrenia patients). Discussion: Until now no single pharmacological augmentation strategy to clozapine has been proven superior to other in double-blind randomized, large-scale placebo-controlled data. Electroconvulsive therapy seems to be the only non-pharmacological technique with enough data to support its efficacy in ultra-resistant cases of schizophrenia. Other neuromodulatory techniques, like tDCS, are still in early phase of investigation, and psychotherapy does not have enough evidence to support its efficacy. [ABSTRACT FROM AUTHOR]

Background: Psychosis is a clinical syndrome which can have detrimental effects on patients in different aspects of functioning such as thought, behavior, and cognition. Even in early phases psychotic spectrum illnesses like schizophrenia, patients can experience cognitive decline prior to overt classical symptoms like delusions and hallucinations. Early detection and reducing the duration of untreated psychosis through early intervention can prevent or slow the progress of cognitive symptoms and the entire illness. Although cognition research in early psychosis has demonstrated that verbal memory is one the first cognitive domains impacted in first-episode of psychosis and continuously declines after the first-episode, it is still not clear which tests are most widely used to measure verbal memory and which may be most amenable to being translated to a digital format. In this systematic review, we assessed which verbal memory assessments are most widely used in first-episode psychosis and may be potentially applied via digital technologies (smartphone applications, telepsychiatry, chatbots, etc.) for use in early detection in the future. Methods: From September to November 2019, we searched studies measured verbal memory in first-episode psychosis or schizophrenia over the past 10 years on PubMed and PsycINFO. We screened abstracts of these studies and we excluded review studies and duplicates. We downloaded fulltexts of included studies to identify the verbal memory measurement tests used, follow-up frequencies, and sample sizes. Results: We screened 233 papers and found that 121 original research studies measured verbal memory in first-episode psychosis over the past 10 years. Of these 121 studies, 32(%26) used Rey Auditory Verbal Learning Test (RAVLT), 29(24%) used California Verbal Learning Test (CVLT), 27(22%) used Weschler Memory Scale (WMS), 14(12%) used Hopkins Verbal Learning Test (HVLT), 4(3%) used both WMS and CVLT, 3(2%) used both WMS and RAVLT, and 12(%10) used other tests to measure verbal memory. Four (3%) of these studies specified that they used a computer, 23(20%) used paper-pen, 2(2%) studies used both, and 92(76%) studies did not specify their verbal measurement application tools. Thirty-six (30%) studies had follow-up measurements of verbal memory, while 85(70%) studies had only a single time point verbal memory measurement during the study period. Study sample sizes range from 6 to 498. Discussion: We found that four main tests to measure verbal memory in first-episode psychosis are RAVLT, CVLT, WMS, and HVLT although they are not often administered via technology. Of these four verbal memory measurement tests, RAVLT is the most widely used and HVLT is easier to administer while CVLT appears able to assess a broader range of verbal memory domains. There is an emerging opportunity to apply RAVLT, CVLT, WMS, and HVLT via digital technologies for expanding access to early detection of cognitive decline in clinical high risk and first-episode psychosis. [ABSTRACT FROM AUTHOR]

Background Childhood adversity is strongly associated with increased risk for psychosis. Research on the relationship between childhood adversity and psychosis not only links childhood abuse and neglect to psychotic symptoms, specifically hallucinations, but also indicates that the relationship is causal, with a dose-effect. Preliminary evidence of this relationship has been replicated within the clinical high risk (CHR) population through the North American Prodrome Longitudinal Study (NAPLS) where, relative to controls, individuals at CHR reported having experienced significantly more trauma and bullying, resulting in higher levels of anxiety and depression, as well as poorer functioning. Indices of stressful life events, family history of psychotic illness, and trauma represent robust predictors for presence of CHR syndrome and are included as part of the NAPLS Individualized Risk Calculator for Psychosis. Despite clear evidence for an association between childhood trauma and psychosis, the biological mechanisms that mediate this relationship remain largely unknown. Previous research has implicated the role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in development of both physical and mental illness. The HPA axis is highly responsive to environmental adversities both in childhood and in adulthood. Further, the HPA-axis is known to be a powerful modulator of inflammatory activity, as measured by peripheral markers of inflammation, and is in turn modulated by inflammatory processes. Immune system activation and dysregulation may serve as a biological mediator between childhood trauma and vulnerability for developing psychosis. The aim of this paper is to establish whether early-life adversity is associated with a pro-inflammatory phenotype in individuals at CHR for psychosis using a validated multiplex blood assay index previously established by Perkins et al. (2014). Methods 35 healthy controls and 62 CHR subjects (N=117) that participated in the NAPLS2 study, ages 12–35, were included. 32 of the CHR subjects later converted to psychosis. Experience of trauma was assessed using the Childhood Trauma and Abuse Scale, a semi‐structured interview used to detect the occurrence of psychological bullying, physical bullying, emotional neglect, physical abuse, psychological abuse, or sexual abuse, before the age of 16. Experience and sensitivity to stressful life events was assessed using a modified version of the Life Events Scale (LES). Subjective stress for endorsed items is coded on a 7-point Likert scale. Inflammation and oxidative stress were measured using a 15-analyte blood biomarker index previously established to reliably distinguish between healthy control subjects, CHR subjects who developed psychosis, and CHR subjects who did not develop psychosis. Results Across subjects, the 15-analyte index was significantly correlated with total number of unique traumas endorsed. Increased trauma exposure was associated with a higher analyte index value (r=.26, p< 0.01). Additionally, the 15-analyte index was significantly correlated with total number of reported undesirable life events (r=.20, p<0.05), as well as subjective level of stress to events (r=.26, p=0.01). Higher incidence of stressful life events, and increased level of subjective stress were associated with a higher analyte index value. Discussion These results provide preliminary evidence for an association between blood-based markers of inflammation, oxidative stress, and early-life adversity. Greater exposure to trauma, higher incidence of stressful life events, and increased levels of subjective stress to life events may be predictive of later life immune system activation. [ABSTRACT FROM AUTHOR]

Background Although the clinical high risk (CHR) for psychosis paradigm has become well-established over the past two decades, one key component has received surprisingly little direct investigative attention: the validity of the conversion to psychosis or transition criteria. This lack of evidence is surprising because many CHR treatment and prediction studies rely on the conversion measure as an outcome. In the absence of such evidence, some observers have raised the possibility that conversions from CHR may be trivial. The aim of this study is to evaluate the predictive validity of the transition to psychosis as measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR individuals. To our knowledge, this is the first study to examine the CHR conversion to psychosis at one-year follow-up. It is hypothesized that CHR participants whose conversion to frank psychosis was ascertained by SIPS (SIPS CV) will show similar diagnostic stability and severity of illness compared to the FEP sample and will differ significantly from SIPS Non-Converters (NCV) on clinical severity. Methods Participants included 33 SIPS Converters (CV) (met criteria for conversion to frank psychosis (COPS) on SIPS) and 399 CHR NCV both from the North American Prodromal Longitudinal Study (NAPLS 2), as well as a sample of 67 separately-ascertained first-episode psychosis (FEP) patients from the STEP Coordinated Specialty Care (CSC) program in New Haven, CT. Comparisons using Chi-square and ANOVA were made at baseline and one-year follow-up on variables from demographic, diagnostic stability (SCID) and available measurement domains relating to severity of illness (psychotropic medication and resource utilization). Results The principal findings of the present study are: 1) large majority of cases in both SIPS CV (n=27/33, 81.8%) and FEP (n=57/67, 85.1%) samples continued to have current psychosis diagnoses at one year follow up, 2) exposure to antipsychotic medication was higher in SIPS CVs (n=17/32, 53.1%) compared to SIPS NCVs (n=81/397, 20.4%), and similar as compared to FEP cases (n=39/65, 60%), 3) at follow up, SIPS CV had higher rates of resource utilization (any psychiatric hospitalizations, day hospital admissions, and ER visits) than SIPS-NCV and were similar to FEP in most categories. Discussion The results suggest that the SIPS definition of psychosis onset carries substantial validity in that those with SIPS-defined psychosis demonstrate similar diagnostic stability and severity of illness at one-year follow as a first episode sample and greater severity of illness as compared to a SIPS-defined CHR con-converting sample. Limitations include the lack of functional assessments at follow-up in the SIPS-CV. Additional studies are needed to further validate the CHR vs transition to psychosis distinction. Since many patients who come to baseline evaluation for CHR are discovered to have previously unrecognized frank psychosis, future studies should aim to obtain additional evidence by following this important group. [ABSTRACT FROM AUTHOR]

Background Patients diagnosed with schizophrenia have a higher risk for suicide than general population, and the elevated prevalence of suicidal ideation and attempts represents a challenge for this population. Data in the literature sustain a lifetime risk of suicide in schizophrenia between 5 and 15%, and the rate of suicide attempts is even higher, varying from 20 to 40%. Suicide ideation and suicide attempts are observed in patients both during acute phase of schizophrenia spectrum disorder and between psychotic episodes. Post-psychotic depression, affective symptoms within psychotic acute episodes, specific positive symptoms that could trigger suicide behaviors, and co-morbid substance use disorders are the most supported suicide risk factors. Methods A literature search was performed in the main electronic databases (Cochrane, PubMed, EMBASE, CINAHL, Thomson Reuters/Web of Science) using as keywords "suicide risk", "suicide ideation", "suicide attempts", "schizophrenia", "schizoaffective disorder", and "psychotic disorders". All papers published between 1998 and 2018 have been included in the primary analysis. Inclusion criteria: observational, interventional, randomized, single/double-blind or open trial, national registry analysis, retrospective chart analysis or outpatient recordings review; age between 18 and 65; patients diagnosed with schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified who presented at least one episode of suicidal ideation or at least one suicide attempt; use of structured methods for evaluation of the suicide risk. Exclusion criteria: unspecified trial design, case reports, case series, systematic reviews and meta-analyses, age under 18 and above 65, multiple somatic and psychiatric co-morbidities, lack of a specified instrument for suicide risk evaluation. Results A number of 82 papers were found after the primary search, but only 4 remained after inclusion and exclusion criteria filters were applied. These four papers were retrospective analyses based on hospital charts and outpatients' recordings analysis (n=3), and one prospective clinical trial. A total number of 17,582 patients diagnosed with schizophrenia and related disorders were included in these four papers. Higher Calgary Depression Scale for Schizophrenia (CDSS) score, anxiety, guilt, gender, age, number of previous hospitalizations, previous suicide attempts, financial or relationship losses, multiple psychiatric co-morbidities were the most reported risk factors for suicide in schizophrenia spectrum disorders. Discussion Patients diagnosed with schizophrenia spectrum disorders should be carefully evaluated and monitored for suicide risk. The use of structured interviews and/or validated scales for suicide ideation and behaviors may be very helpful in the early detection of patients at risk, especially in the context of communicational difficulties frequently observed in psychoses. [ABSTRACT FROM AUTHOR]

Background Although nosologically distinct, there is overlap in the disease presentation of individuals with schizophrenia (Sz) and bipolar disorder (BD). Both disorders are characterized by abnormalities in cognitive performance, and in brain volume, cortical thickness and surface area. It is possible that these abnormalities are related, however the nature of the brain structure-cognition relationship in these disorders is inconclusive. This review aims to elucidate the association between measures of brain morphology and cognitive impairment in Sz and BD. Methods Science Direct, PubMed, NCBI, and Web of Science databases were searched for papers investigating cognition and brain morphology in Sz and BD. Results Studies indicate that grey matter volume is generally positively associated with cognitive performance. Evidence suggests common positive relationships between premorbid IQ and volume of the frontal lobe, current IQ and the temporal lobe, and verbal memory/learning and hippocampal and amygdala volume. Positive thickness-cognition relationships included non-specific executive functioning and the frontal region, attention and the temporal region, and verbal learning and memory and the temporal region, specifically the right superior gyrus. Only a handful of studies have investigated surface area with regards to cognitive impairment in Sz and BD and observed positive relationships between premorbid IQ and the frontal region, and current IQ and the temporal region. Discussion Limitations of the literature stem from methodological and sampling issues, and from the disproportionate number of schizophrenia to bipolar disorder studies. There is a need for more novel approaches to uncover the nature of brain morphology-cognition relationships in BD and Sz. [ABSTRACT FROM AUTHOR]

Background: Specialized early intervention services (EIS) for psychosis have been shown to have superior outcomes compared to routine care. However, these gains are often lost when care is transferred to community mental health care teams. Research has shown that young adults experience anxiety, worry and stigma around the transition process from EIS, which can impact ongoing engagement with treatment. Transition to a new care team has been shown to be a time for disengagement. Despite this area’s acknowledged importance, there is a paucity of literature on how to maintain engagement during the transition process from an EIS to community services. We conducted a qualitative study with EIS for psychosis patients in various phases of transition which informed the development of a peer support program focused on the transition time period. Methods: Focus groups were conducted to identify strengths and weaknesses of the transition process from a Canadian EIS program. Thematic analysis was conducted on the transcripts from the focus groups. Following themes from the focus groups, a research study was developed to create and evaluate a peer support worker (PSW) program for individuals in transition from the EIS. Peer support workers were recruited from individuals who had successfully transitioned from the same five year EIS for psychosis program. Individuals underwent training as peer support workers that was tailored to the needs of individuals with a psychotic disorder. Peer support workers met with clients in both clinical and community settings with support and feedback provided by clinicians in the EIS. Results: Strengths identified included preparation time, helping individuals feel stable prior to transition and inclusion in decision making. Weaknesses included communication, more individualized preparation for transition and a desire for more opportunities to build independence and responsibility. A major theme was lack of peer support during the process, with a voiced desire to maintain connection to EIS by being a peer mentor in those who had already transitioned out. We recruited 7 individuals interested in becoming PSW and with a PSACC Certified Peer Support Mentor, designed a curriculum for training based on his peer support training experience with feedback from clinicians to customize it to the experience of living with psychosis and transition. The features of this curriculum will be discussed. 5 of 7 individuals completed training. 4 expressed an interest in being hired. 1 was not able to complete the hiring process but did an exit interview and impediments to hiring included costs associated with hiring practices that needed to be paid up front then reimbursed, limited internet access to a secure connection that allowed HR software to function and transportation issues. 3 individuals were hired as PSW (2F,1M) and supported participants transitioning from our clinic who were interested. PSW would meet in the clinic with individuals prior to transition then support them in the community for several months after transition. 1 PSW relapsed during the course of the study. Only 1 PSW has continued with our program. Patients in transition participating in the program underwent semi-structured interviews that indicated satisfaction with the program. Discussion: At project launch, we examined the literature and could only find one paper related to the concept of PSW and transition in psychosis. Having lived the process of developing the program, we gained an understanding of the difficulties of enacting what we have found to be a highly successful adjunct to our program. PSW programs involving individuals with psychosis are expensive to launch and attrition is high but these costs need to be weighed against improved transition outcomes. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SZ) patients show activity deficits in brain regions that are conventionally associated with time perception. The dysfunction observed during timing tasks partially coincides with that evidenced during change-detection ones (both of attentional processing during odball paradigm and of preattentional processing in the mismatch negativity response). The implication is that timing dysfunction might underlie aberrant Salience Network (SN) and therefore cognitive impairment observed in SZ. In order to support this idea, we would like to examine it in HC. We hypothesize that neuroanatomical bases of time and salience processing are highly shared and interrelated not only in SZ but also in HC. The principal objective of this study was to elucidate whether there are any brain regions that show overlapped response during timing and oddball tasks in HC. Methods: We conducted three independent comprehensive literature searches of whole-brain functional magnetic resonance imaging (fMRI) studies in HC using timing and oddball tasks. The searches were applied to the PubMed search engine up to October 2019. Keywords used in the first search were: ((“Temporal processing” OR “temporal discrimination” OR “time perception” OR “temporal estimation” OR “time estimation” OR “internal clock” OR “interval timing” OR “timing”) AND (“functional magnetic resonance imaging” OR “fMRI”) AND (“healthy volunteers” OR “healthy comparison” OR “healthy adult participants” OR “healthy comparison subjects” OR “healthy control subjects” OR “healthy subjects” OR “healthy individuals” OR “healthy participants” OR “healthy controls” OR “healthy” OR “controls” OR “control subjects”)). Keywords used in the second search were: ((“oddball”) AND (“event-related”)) together with the terms mentioned above referring to HC and fMRI. Last search used the same keywords but combined with (“mismatch negativity” OR “MMN”). We excluded studies that 1) used a region-of-interest approach; 2) did not report peak coordinates; 3) used different statistical thresholds in different regions of the brain; 4) used techniques other than fMRI; 5) were case reports, qualitative studies, reviews or meta-analyses. We ran three signed differential mapping (SDM) meta-analyses of fMRI studies assessing the brain response to timing and oddball paradigm in HC. Then, we carried out a multimodal meta-analysis to combine the findings from the three previous SDM meta-analyses. Results: Our initial search returned several papers, but application of inclusion criteria reduced this number to 17. Among them, 8 studied timing (which included a total of 129 HC), 8 examined attentional oddball paradigm (which included a total of 125 HC) and 3 MMN (which included a total of 52 HC). Meta -analysis results of timing studies HC showed significantly activation in left supplementary motor area (BA 8), left middle frontal gyrus (BA 10), right inferior frontal gyrus (BA 45), right supramarginal gyrus (BA 40), corpus callosum, left inferior network, left striatum, right superior longitudinal fasciculus and left cerebellum. Meta-analysis results of attentional oddball paradigm studies HC showed significantly activation in right supplementary motor area (BA 32), left postcentral gyrus (BA2), right rolandic operculum (BA 48), right supramarginal gyrus (BA 40) and left insula (BA 48). Meta-analysis results of preattentional oddball paradigm studies HC showed significantly activation in corpus callosum. Discussion: The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing and oddball tasks in HC. Since timing might be a primary cognitive function, its better understanding could help to improve the approach of treatment in SZ. [ABSTRACT FROM AUTHOR]

Background: About a third of the world’s population will develop a mental disorder over their lifetime. Having a mental disorder is a huge burden in health loss and cost for the individual, but also for society because of treatment cost, production loss and caregivers’ cost. The objective of this study is to synthesize the international published literature on the economic burden of mental disorders. Methods: Systematic literature searches were conducted in the databases PubMed, Embase, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to 1980 until May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder (3) samples based on the general population; (4) outcome in monetary units. 13,640 publications were screened by their title/abstract and 439 articles were full-text screened by two independent reviewers. 113 articles were included from the systematic searches and 31 articles from snowball searching, giving a total of 144 included articles. Of these, 41 studies had estimates of the economic burden among people with schizophrenia. Results: Information about diagnosis, diagnostic criteria, sample size, age, sex, data sources, study perspective, study period, costing approach, cost categories, discount rate and production loss method and cost unit was extracted. The preliminary results show a substantial variety in the used perspective, methodology, costs components and outcomes in the included studies. An online tool is under development enabling the reader to explore the published information on costs by type of mental disorder, subgroups, country, methodology, and study quality. Discussion: To the best of our knowledge, this is the first systematic review synthesizing the economic cost of mental disorders worldwide. The paper will provide an important and comprehensive overview over the economic burden of mental disorders, and the output from this review will inform policy-making. [ABSTRACT FROM AUTHOR]

Background: Although the use of technological advances in psychiatric treatment is relatively recent, the availability and sophistication of technologies are growing, research on psychological interventions for patients with psychosis has incorporated the use of various electronic applications, social networks, and other similar tools to provide new methods/routes of communication between therapists and patients. This new therapeutic approach may provide patients with personalized, flexible, and evidence-based interventions in their communities and even in their own homes. The aim of this study is reviewing the scientific literature about the use of online intervention for patients with psychosis to show the current state of online intervention and asses the effectiveness of these treatments. Methods: The review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We have identified articles from Pubmed and Medline databases. We included all randomized controlled trials designed to test the efficacy of the online intervention or web-based intervention to patients with psychosis. We excluded observational trials, non-randomised trial and protocol study. Studies with RCT design and the participants must not have more than 5 to 10 years of evolution since the diagnosis, and the papers have been published between 2010 and 2019, in English language. The researchers independently assessed the articles and the discrepancies were resolved by consensus. Results: We presented data about all randomized controlled trials of online interventions/ e-Health interventions/ App-mobile based and/or computer based intervention programs than were specifically designed for people with first episode psychosis or psychotic symptoms that had measured changes in functioning, quality of life or positive/negative symptoms. As unique treatment or as a complementary treatment with other psychological or psychopharmacology intervention. Discussion: Online psychological interventions can play an important role in the well-being of people with schizophrenia. The strengths and limitations of our systematic review and meta-analysis will be discussed. [ABSTRACT FROM AUTHOR]

Background: Many people with a psychosis diagnosis have significant impairments in their social functioning. Despite this, long standing lack of consensus exists in the definition of social functioning in psychosis. Efforts to evaluate interventions for social functioning are hampered by measurement difficulties, and comparing interventions is difficult. Popular measures of social functioning vary widely, both conceptually and methodologically, and it is unclear how meaningful they are for service users. With the increasing development and evaluation of social interventions for psychosis and the boom in the development of measures, this paper reviews the recently developed measures of social functioning. It aggregates how often and in which studies measures have been used, the concepts and theories that underlie them, as well as assessing their quality across a number of indicators, with a particular focus on how patient-centred they are. Methods: Systematic review and narrative synthesis. Results: 21 new measures of social functioning were identified, of low to moderate quality. The content, definitions, theories and domains will be discussed, as well as a discussion of changes in the construct over time. Discussion will include the development of measures for use in first episode psychosis, measures with a focus on negative symptoms and the increasing use of technology in the assessment of social functioning. Discussion: Many measures exist for assessing social functioning in psychosis, of variable quality. Further attention should be directed to psychometric evaluation and ensuring service user involvement in development [ABSTRACT FROM AUTHOR]

Background: Negative symptoms in schizophrenia are associated with lower quality of life, worse functional prognosis and poorer response to the psychopharmacological treatment [1]. Many efforts have been made to find new approaches for negative symptoms, and neuromodulation techniques may represent a solution for these patients when antipsychotics have reached their limits of efficacy [2]. Transcranial magnetic stimulation (TMS) is based on the use of alternating magnetic fields to induce electrical current in the cortical areas, being mainly used for patients with treatmentresistant depression and it is considered safe and well tolerated [3]. Methods: A narrative review of data regarding the efficacy of transcranial magnetic stimulation for patients with schizophrenia with prominent negative symptoms was performed. Papers published between January 2000 and July 2019 in the main electronic databases (PubMed, Cochrane, EMBASE, CINAHL) were included in this review. The keywords used for database search were “schizophrenia” and “negative symptoms” and “transcranial magnetic stimulation” or “repetitive transcranial magnetic stimulation”. Results: The treatment of negative symptoms in schizophrenia with high frequency TMS has been associated with favorable results in clinical trials. The targeted zones were dorsolateral prefrontal cortex, either bilaterally or only on the left side. The results varied upon the stimulation regimen, including duration, frequency, uni- versus bilaterally application etc. Two meta-analyses were identified and their results supported an effect size from 0.58 to 0.63 [2,3]. However, negative results derived from well designed clinical trials exist, which show no difference in the Positive and Negative Syndromes Scale (PANSS) - negative symptom score between rTMS and sham rTMS [4,5]. An exploratory analysis of a large-scale trial showed the impact of rTMS on different negative symptom domains confirmed no additional beneficial effect of the actove comparative to sham rTMS [5]. Also, data exist about the potential of rTMS for increasing task-related in frontal areas in patients with schizophrenia with negative predominant symptoms, which may grant further exploration of the mechanisms underlying the effects of rTMS. Discussion: Data about the efficacy of TMS in schizophrenia with negative symptoms are controversial, because both evidence to support its efficacy and its lack of efficacy exist in clinical trials. However, meta-analyses support an important size effect which may be comparable to that of the pharmacological treatment. [ABSTRACT FROM AUTHOR]

Background Children and adolescents are more prone to develop adverse effects during antipsychotic treatment than adults. The purpose of this paper iso investigate cardiometabolic effects and its predictors in youth with first-episode psychosis (FEP) treated with quetiapine-extended release (ER) vs. aripiprazole. Methods Youths with FEP aged 12–17 years were randomized to quetiapine-ER or aripiprazole in the 12-week, double-blinded, Tolerability and Efficacy of Antipsychotics (TEA) trial. Primary outcome was change in body weight; secondary outcomes were changes in body mass index (BMI) and waist circumference (WC), blood pressure (BP), heart rate, and lipid and glucose metabolism parameters. Possible predictors of cardiometabolic changes were examined. Results Altogether, 113 patients (schizophrenia-spectrum disorders=93%, age (mean±SD): 15.7±1.4 years, males=30.1%), were randomized to quetiapine-ER (n=55) or aripiprazole (n=58). Quetiapine-ER was associated with significantly larger increases in body weight, BMI z-score and WC z-score than aripiprazole (all between-group p-values p<0.0001): Lipid and glucose metabolism parameters increased significantly at week 4 and 12 only with quetiapine-ER (p-range: 0.0001–0.037). Quetiapine-ER was associated with an increased occurrence of obesity, elevated blood lipids and hyperinsulinemia (p-range=0.004–0.039). Early weight gain, obesity or type 2 diabetes in the family significantly predicted weight and BMI gain at week 12. Discussion In youth with FEP, quetiapine-ER was associated with significantly greater weight gain and adverse changes in metabolic outcomes than aripiprazole. Early weight gain must be addressed and family lifestyle factors taken into consideration when treating youth with antipsychotics. [ABSTRACT FROM AUTHOR]

Background Auditory hallucinations are a hallmark symptom of schizophrenia, with approximately 70% of patients endorsing hallucinations in their lifetime. Of these, 25–30% of patients continue to experience auditory hallucinations despite adequate antipsychotic treatment. In recent years there has been growing interest in adjunct non-invasive neuromodulation therapy for mental health disorders, particularly for the alleviation of medication resistant symptoms by tempering atypical neural activity. Transcranial Direct Current Stimulation (tDCS) is an especially low-risk method that has attracted significant interest for potential treatment of refractory auditory hallucinations. TDCS uses surface electrodes placed on the scalp to administer a gentle electrical current intended to modulate the excitability of underlying cortical regions. With this new area of research quickly widening, there is demand for a more up-to-date understanding of the effects of tDCS on auditory hallucinations in schizophrenia. Methods To address this need, the authors undertook a systematic review and meta-analysis of the literature base in PubMed by using search terms related to schizophrenia, tDCS, and auditory hallucinations. The search, conducted in November of 2018, garnered 54 papers which were screened and reduced to 13 for review. Results Preliminary analyses suggest a significant large negative relationship between tDCS and the incidence of auditory hallucinations in schizophrenia when examining studies with repeated measures designs (d=-1.37, CI: -1.70, -1.03) and a non-significant medium effect on auditory hallucinations in studies with sham-controlled designs (d=-0.53, CI: -1.70, -1.03). Discussion These data suggest a very promising avenue for intervention with relatively no reported adverse effects when compared with sham. Additionally, the authors provide a commentary on the methodological approaches used and discuss directions for future inquiry. [ABSTRACT FROM AUTHOR]

Background Although cognitive impairment is a recognized feature of schizophrenia (SZ) and bipolar disorder (BD), there is increasing evidence to suggest substantial patient-to-patient variation in cognitive ability that may reflect differences in underlying neurobiology. An expanding body of work has focused on probing this hypothesis by examining brain morphological patterns within subgroups of patients with SZ or BD classified using cognitive clustering approaches. This review aimed to summarise this work, with a view to providing insight into the extent to which brain morphological differences map on to cognitive subgroups within these disorders. Methods Science Direct, PubMed, NCBI, and Web of Science databases were searched for papers investigating cognitive subgroups and brain morphology (cortical thickness, surface area and volume) in SZ and BD. Results Twenty-one studies have investigated the presence of cognitive subgroups and associated brain morphology, 16 focusing on SZ, one on BD, and four examining SZ and BD cross-diagnostically. Within these, the subgroup structure of cognitive heterogeneity was generally similar – anchored by a cognitively near-normal subgroup and a severely impaired subgroup. Generally speaking, brain morphological differences were evident between cognitive subgroups and healthy controls, but not between subgroups themselves. When between-subgroup differences were evident, the magnitude of morphological alterations was typically the distinguishing factor rather than the pattern of brain abnormality. The case - control deficits in patients classified as cognitively impaired were more severe and widespread than those classified as cognitively spared/near-normal. Most studies analyzed brain volume, although the general pattern of findings was similar in the few studies that examined cortical thickness and surface area. Discussion Relative to controls, brain morphological differences between cognitive subgroups generally appear to reflect variations in the magnitude of brain abnormality rather than unique patterns of abnormality. This coupled with the presence of morphological alterations in cognitively spared/near-normal patients, suggests that brain abnormalities may map more closely to the presence of psychopathology rather than cognition itself. [ABSTRACT FROM AUTHOR]

Background Schizophrenia (SCZ) is a heritable psychiatric disorder which affects approximately 1% of the population. The disease is characterized by both positive and negative symptoms, as well as declines in cognitive functioning. SCZ often becomes clinically apparent from late adolescence to early adulthood and severely impacts the quality of life. Although treatments exist, the development of preventive or curative interventions is hindered by the lack of mechanistic understanding of the pathophysiology of SCZ. The complement component 4 (C4) gene has been identified as one of the largest effect size markers for SCZ risk (Sekar et al. 2016). Sekar et al. have shown the longer version of C4A (C4AL) is linked with higher neural C4A expression which is associated with higher SCZ risk. The C4 gene discovery opened a new direction in SCZ research. This study aims to further explore the relationship between C4 structural variations and clinical characteristics in our Toronto Schizophrenia sample. Methods 599 adults (age 18+) with SCZ or schizoaffective disorder were recruited from our CAMH hospital. Clinical and demographic information was gathered through structured clinical interviews (SCID) and chart review. The copy numbers of the C4A, C4B, C4L, and C4S in each sample were determined using ABI TaqMan copy number variation (CNV) protocol. Also, C4 CNV data on healthy controls were obtained on a small preliminary sample (n=111) from the Sekar et al. paper. Fisher's exact test was performed to compare C4 CNV distribution between patients and controls. Linear and binomial logistic regression were performed to assess the relationship between C4 CNV and clinical characteristics of SCZ. The additive genotypic model in the analyses and sex was adjusted in the model of the age of onset. All statistical analyses were conducted using IBM SPSS software. Results The CNV counts of C4 structural variants in our sample ranges from 0–6, 0–5, 0–6, and 0–4 for C4A, C4B, C4L, and C4S respectively. No significant difference was observed in C4 CNV distribution between patients and healthy controls (p = 0.866, 0.795, 0.570, 0.430 for C4A, C4B, C4L, and C4S respectively). Age of onset was the only clinical characteristic that showed nominal association with C4A CNV, and the effect became more robust with sex was as a covariate (p = 0.05, p = 0.008, adjusted for sex). There was no significant association observed between C4 CNV and other clinical characteristics tested, such as symptom severity; Global Assessment of Function; and presence of symptoms such as delusions, hallucinations, disorganized speech or behavior, catatonia, alogia, avolition, inappropriate affect, and affective flattening. Discussion In the brain, C4 plays a crucial role in synaptic pruning. The process of synaptic pruning reaches a peak in late adolescence which is the same time when SCZ becomes clinically apparent. Synaptic pruning also explains the deficit of synaptic connections, as well as the cognitive decline that is commonly seen in SCZ. Sekar et al. previously identified the combination of C4A and the retroviral insertion creating - long version (C4AL) as a risk haplotype for SCZ. In our sample, we found no difference in C4 CNV distribution between patients and healthy control. Age of onset was the only clinical characteristic showed nominal significance with CA4 CNV, but the finding is contrary to the current knowledge of C4 in SCZ. Our results suggested higher C4A copy number leads to a later age of onset. The lack of significant finds could be due to the discordance in ancestry between patients and healthy controls, and small sample size. The next step is to estimate neural C4A expression using C4 structural haplotype data and explore the roles of neural C4A expression in SCZ risk and phenotypes. [ABSTRACT FROM AUTHOR]

Background The Prodromal Questionnaire-16 (PQ-16; Ising et al. 2012) is a measure used to screen for attenuated psychotic symptoms that may indicate the presence of the at-risk mental state. The PQ-16 has been validated for use in help-seeking populations and the structure of the measure in this population is categorized by three subscales. These are perceptual abnormalities/hallucinations subscale, the unusual thought content/paranoia subscale, and negative symptoms subscale. The present study aimed to examine the structure of the PQ-16 in a non-help-seeking population through exploratory factor analysis and a confirmatory factor analysis. Methods Participants (n=722) were recruited through Amazon's Mechanical Turk (MTurk) and completed the PQ-16 as part of a battery of questionnaires. For the exploratory factor analysis, the mean age of the sample was 27.93 years (SD=4.8), 55% of the sample were male, and 49% were single. The exploratory factor analysis, using principal axis factoring and oblique rotation, indicated a two-factor model was suitable for the PQ-16 in this population. Based on the current study and previous studies, three separate confirmatory factor models will be analyzed using SPSS Amos Version 25. Results The exploratory factor analysis indicated that there was a two-factor model suitable for this sample. Factor 1 appeared to represent perceptual abnormalities/hallucinations, while factor 2 was interpreted as general symptoms. Factor loadings indicated that items 2 & 14 of the PQ-16 did not fit into either factor and were excluded from the two-factor confirmatory factor model. Exploratory factor analysis has been completed, and confirmatory factor analysis of the PQ-16 in a similar non-help-seeking population is underway. Discussion The exploratory factor analysis indicated that a two-factor model is suitable for this sample (Factor 1 representing perceptual abnormalities/hallucinations; factor 2 representing general symptoms). The confirmatory factor analysis will allow us to explore what model is the best fit for the PQ-16 in this population. [ABSTRACT FROM AUTHOR]

Background Suicide is serious health issue and frequently one of the leading causes of death around the world. Suicidal behavior has three stages—ideation, attempt and completion. Since suicide ideation (SI) predicts attempt, it is an important indicator that has been extensively investigated. Studies have found childhood trauma and various forms of stress as robust risk factors for suicide ideation and behavior. However, to our knowledge, there has not been a direct comparison of childhood trauma and stress that would determine if one has a greater effect on current SI than the other. For our study, the goal is to identify whether childhood trauma affects current ideation in people that are presently experiencing stress. Methods A total of 163 participants were selected from an existing schizophrenia database. All were previously interviewed and completed the Childhood Trauma Questionnaire (CTQ), the Columbia-Suicide Severity Rating Scale (CSSRS), and the Holmes and Rahe Stress Scale (HR) during a one-time cross-sectional assessment. The CSSRS was administered for scoring suicidal ideation in the last month. The CTQ was administered to assess the history of childhood trauma and HR was used to assess stressful life events in the last three months. Data analysis was performed to assess whether the presence of traumatic experiences in childhood and current stress interact in conferring risk for current suicidal ideation. Results There was no significant interaction (p>0.05) between childhood trauma and recent stress in conferring risk for current suicidal ideation. Discussion Even though, we could not prove any additive effect of childhood trauma and recent stressful events in conferring risk for current suicidal ideation in our sample, the development of predictive algorithms that combine proximal and distal stressful events can improve the assessment of psychotic patients at risk of suicide. [ABSTRACT FROM AUTHOR]

Background Social cognition (SC) can be defined as the domain of cognition that involves the perception, interpretation, and processing of social information. It has a close relationship with deficits daily life functions in schizophrenic disorders. Theory of Mind (TOM) plays an important role in SC. The neuroscience or neuropathway of SC remains unknown despite advances in neuroimaging techniques. The present systematic review on neuroimaging studies aims to explore and construct the neuro-circuitry that is related to social cognition, especially ToM. The specific objectives are to 1) conduct a systematic review on neuroanatomical sites related to ToM in schizophrenia in comparison to healthy subjects, and 2) construct and propose neuropathways which are associated with ToM in schizophrenia, and 3) suggest directions for future research. Methods This review followed the latest PRISMA guidelines using Pubmed, PsychINFO and Scopus databases from 1990 to the present. Ten studies met the key inclusion criteria: 1) involved patients with schizophrenia or healthy human subjects from 18–60 years; 2) studied neuroanatomical sites; 3) were experimental in nature; 4) consisted of brain activity study associated with ToM related tasks (e.g. false belief, social animations, mind in the eyes tasks, etc); 5) included neuroimaging techniques such as MRI, PET, etc, and 6) were written in English. Articles as if they were: 1) review paper; 2) animal study; and 3) used descriptive research methods (e.g. case study, etc.) or were cross-sectional study. Results Results showed that ToM pathways had both rational and irrational/emotional components and involved TPJ, STS, STG/MTG, fusiform gyrus, DLPFC, ILPFC, PCun, ACC and Amygdala in schizophrenia. The neuroanatomical sites were classified into three categories depending on their functions following the information processing model. Thalamus, occipital lobe and temporal lobe were involved with the receiving process. Precuneus, MTG/STG, Fusiform gyrus, TPJ, STS, ACC, DMPFC, OFC/VMPFC and Amygdala were the processing components. Lastly, DLPFC, ILPFC, frontal lobe and SMA were involved in the efferent process. The review also showed the different results for brain activation of neuroimaging studies investigating TOM for schizophrenia subjects are compared to the healthy controls that showed schizophrenic patients had less active than healthy participants in neuroanatomy of ToM which are right Thalamus and right ACC; then came to the left TPJ, right insula, right striatum, right cerebellum and bilateral mPFC. Meanwhile, there were three out of ten studies with the results showing that schizophrenic patients had higher activity than healthy participants in the neuroanatomy of ToM which are left STG/MTG, right mPFC, right Supplementary motor area, right precuneus, right ILFC and Thalamus. Discussion This is the first attempt to explore the detailed neuropathways of social cognition in relation to social activity in schizophrenia. We constructed neuropathways which are associated with ToM in schizophrenia. The proposed pathway, however, has to be verified by well-designed functional magnetic resonance imaging (fMRI) studies. Both functional and structural connectivity should be studied to assess the integrity of the connectivity between and within areas involved. Meanwhile, longitudinal studies are required to identify how the proposed neurocircuits are evolved over the course of illness parallel to brain abnormalities. This helps develop more effective therapeutic interventions to rectify dysfunction and meanwhile to achieve better interpersonal and community functioning. [ABSTRACT FROM AUTHOR]

Background: Negative symptoms are prevalent and predictive of clinical and functional outcomes across different phases of psychotic disorders. Yet, heterogeneity in conceptualizing the latent structure of negative symptoms presents hindrances to the development of effective interventions. While a 2-dimensional construct of negative symptoms (i.e., Motivation and pleasure [MAP] and Emotional expressivity [EXP] dimensions) have previously been derived from exploratory factor analyses and adopted widely in research, conflicting findings in favor of a 5-factor structure have emerged from confirmatory factor analyses recently. Further evidence is needed to evaluate whether this conclusion can be generalized to the prodromal and early phases of psychosis. Methods: Data were drawn from 3 studies that administered the Brief Negative Symptom Scale (BNSS), a second-generation clinical rating instrument, to assess negative symptoms in Chinese patients with early psychosis or clinical high-risk for psychosis (CHR) in Hong Kong. The early psychosis sample comprised 131 and 246 outpatients recruited in 2 separate studies who received treatment within 5 years since service entry for first-episode psychosis, whereas the CHR sample included 110 help-seeking individuals ascertained using CAARMS criteria. Confirmatory factor analyses (CFAs) were employed to examine competing hypotheses about the factor structure of negative symptoms as measured by BNSS. The fit of five competing models were evaluated, including 1) a unifactorial model, 2) a 2-factor model with EXP and MAP factors, 3) a 3-factor model proposed by Garcia-Portilla et al. (anhedonia and asociality, avolition and blunted affect, and alogia), 4) a 5-factor model specifying the five NIMH consensus development conference domains (blunted affect, alogia, anhedonia, avolition, asociality), and 5) a hierarchical model with two second order-factors reflecting EXP and MAP, and five first-order factors reflecting the five consensus domains. Results: In the early psychosis sample, the 1-, 2-, and 3-factor models provided poor fit for the data. The 5-factor and hierarchical models were excellent fit, with the hierarchical model being slightly more parsimonious. Similarly, CFA of the CHR sample demonstrated that the 1-, 2-, and 3-factor models were poor fit for the BNSS, whereas the 5-factor and hierarchical models provided strong fit. The 5-factor model is slightly favored over the hierarchical model in the CHR sample. Discussion: Similar to results obtained from chronic schizophrenia patients in previous CFA studies, the current findings suggest that the 5 consensus domains are fundamental to the conceptualization of negative symptoms in the prodromal and early phases of psychosis. The current practice of conceptualizing negative symptoms as a two-dimensional construct may preclude information that reflects the narrower facets of idiosyncratic symptom profiles and facilitates functional recovery. [ABSTRACT FROM AUTHOR]

Background: In recent years, antipsychotic-induced weight gain (AIWG) has gained more attention in research. Although interventions to prevent weight gain are currently being investigated, AIWG remains a major problem for both patients and clinicians and often results in poor treatment adherence, a decrease in quality of life. Furthermore, schizophrenia is associated with higher mortality rates and a decreased life expectancy. Recently, some new antipsychotic drugs have been introduced that are hypothesised to entail no or low incidences of clinically relevant weight gain (CRWG), and high incidences of clinically relevant weight loss (CRWL). Here ‘clinically relevant’ is defined as >7% weight change. In this meta-analysis, we aim to give a complete overview of both CRWG and CRWL, including these newer antipsychotics. Methods: We searched Pubmed, Embase and Psychinfo for randomized clinical trials of antipsychotics that reported 7% weight change in study populations aged 18 years or older. We performed meta-analyses stratified by study duration (<6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks) with a random effects model. Results: The search yielded in total 941 articles. Ninety-two articles could be included in the meta-analysis, resulting in 341 records in the data set. All data were related to AP switch patients, no data on AP-naïve patients were found. During SIRS final results will be presented. Preliminary results showed that haloperidol, paliperidone and quetiapine had relatively low CRWG (16.6%, 18.7% and 18.4%, respectively), aripiprazole and risperidone had relatively high percentages of CRWG (25.4% and 24.0%, respectively). Olanzapine (29.5%) and lurasidone (7.4%) resulted in respectively the highest and lowest CRWG at >38 weeks of treatment. In the placebo group, CRWG was 3.8%. Incidences of CRWG continued to rise even after 38 weeks of treatment in most treatment groups. CRWL occurred with all antipsychotic drugs; at 6–16 weeks aripiprazole (7.9%) and ziprasidone (7.1%) had CRWL similar to placebo (8.7%). We found insufficient data on CRWL in the long term (>38 weeks) to draw any conclusions. Discussion: All antipsychotics can result in both weight gain and weight loss. Previous research showed that patients more often gain weight than lose weight (Bak, 2014) and this is replicated in the present meta-analysis. Proportions CRWG and CRWL seem different between the antipsychotics. Future network meta-analysis are needed to test statistical significance of those differences. It appears, however, that CRWG is higher in patients receiving antipsychotics drugs compared to placebo. No conclusions can be drawn on CRWL due to insufficient data. It is clear that after >38 weeks of treatment, no ‘plateau’ phase is reached as CRWG continued to increase. More future research is needed on long-term weight effects on both CRWG and CRWL to give a clear overview on the ‘real’ effects on weight, as the majority of studies had a duration of less than 26 weeks. Furthermore, more research is needed on the long-term dose-response relationship in CRWG, as this could prove to be a method for managing weight in some patients. [ABSTRACT FROM AUTHOR]

Background: There is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed information on connectivity abnormalities in psychiatric disorders such as schizophrenia. Methods: The current study investigated dynamic FC in a sample of 80 schizophrenia patients and 80 matched healthy control subjects. Furthermore, relationships with auditory verbal hallucinations (AVH), a core symptom of schizophrenia, were explored. Two measures of AVH were used, one measure of current AVH severity assessed on the day of scanning, and one trait-measure where AVH were assessed repeatedly over the course of one year. Results: Compared to healthy controls, schizophrenia patients showed increased dwell times in states with high connectivity within the default mode network (DMN). Current AVH severity did not show a significant relationship with dynamic FC. However, the trait-measure of AVH proneness over one year showed a significant relationship with dynamic FC. Patients with high AVH proneness spent less time in connectivity states characterized by strong anti-correlation between the DMN and task-positive networks. Discussion: The results provide further evidence for a DMN dysfunction in schizophrenia, which could be linked to thought disturbances in relation to an increased internal focus of cognitive processing. The effects of AVH proneness on dynamic FC support theoretical models of AVH which have proposed an instability of the DMN and impaired cognitive control in AVH patients. The results also point to AVH proneness as a potential marker for identifying distinct subgroups of schizophrenia patients. [ABSTRACT FROM AUTHOR]

Background: About 1 in 5 youth have a mental illness, with 75 percent of all mental illnesses having their onset in childhood or adolescence (Kim- Cohen et al., 2003). In Ontario, 157,900 youth rated their mental health as fair or poor, a significant increase from 2007 (Boak et al., 2014). Not only do mental health concerns cause difficulties at onset, they can also disrupt important life transitions and developmental milestones, as well as being burdensome throughout the individual’s lifespan (Ratnasingham et al., 2012). Consequently, new care approaches are needed. The TELEPROM-Y project will evaluate outpatient health care delivery using InputHealth’s electronic Collaborative Health Record (CHR) at London Health Sciences Centre, St. Joseph’s Health Care London, Woodstock General Hospital, and community agencies including Youth Opportunities Unlimited, WAYS Mental Health Support, and Leads Employment Services. Methods: 120 youth (ages 14–25) will be recruited from the caseloads of 46 mental healthcare providers. Participants will use a smartphone application (app) to connect to the Collaborative Health Record. Semi-structured interviews will be conducted at baseline, 6, and 12 months. This is a participatory action research project utilizing a pre-post, mixed-methods design. A standardized evaluation framework will be instituted to facilitate systematic effectiveness, economic, ethical, and policy analyses. Some of the functions of the app, available for Apple and Android phones, include: making/changing/cancelling appointments; text messaging; emailing, and filling out questionnaires/surveys. If the youth are unable to attend a scheduled appointment in person, the care-provider and youth can have a virtual visit, similar to FaceTime or Skype. Virtual visits should reduce missed appointments. Results: Descriptive information thus far of 104 participants: Psychotic Disorder (e.g. schizophrenia) (13, 12.6%), Developmental handicap (e.g. Autism) (7, 6.8%), Anxiety Disorder (e.g. PTSD) (73, 70.9%), Disorder of childhood/adolescence (e.g. ADHD) (37, 35.9%), Substance-related disorder (13, 12.6%), Personality Disorder (17, 16.5%), Mood Disorder (e.g. depression, bipolar mood disorder) (70, 68.0%), Unknown (4, 3.9%), Other (19, 18.4%). Discussion: We anticipate that through the usage of the TELEPROM-Y app the participant and care-provider experience will be enhanced, leading to 1) improved healthcare outcomes and patient quality of life, and 2) reduced healthcare costs by preventing hospitalization and reducing the need for face-to-face outpatient visits. [ABSTRACT FROM AUTHOR]

Background: Intrinsic motivation (IM) deficits are a prominent feature of schizophrenia that substantially impacts functional outcome. Previous investigations have primarily assessed IM as a general construct or towards specific activities, but multifaceted examination of IM using objective and ecologically valid means has been lacking. The current study aimed to determine whether IM-driven real-world behaviours of individuals with and without schizophrenia reveal distinct behavioural phenotypes that predict differential clinical and functional profiles. Methods: Forty-five stable adult outpatients with schizophrenia or schizoaffective disorder (SZ) and 47 healthy controls (HC), group-matched for age and sex, completed the study. Wireless motion capture was used to quantify participants’ behaviour (during two previously validated 15-minute open-field tasks) aligning with distinct aspects of IM: exploratory behaviour (in an unfamiliar setting that contained common and uncommon objects) and unincentivized activity engagement (under provision of explicit choice between active versus passive engagement options). Sparse k-means clustering was applied to task-derived indices of locomotion and object exploration, and activity duration, intensity, and persistence to identify behaviourally differentiable subgroups. Clusters were compared across standard clinical measures of general amotivation, cognition, and community functioning. Diagnostic group by cluster assignment interaction effects were evaluated to identify potential discrepancies in withincluster SZ versus HC differences across clusters. Results: Three clusters emerged: medium activity and low exploration (20 SZ and 19 HC), low activity and medium exploration (15 SZ and 8 HC), and high activity and exploration (10 SZ and 20 HC). Cluster assignment did not significantly predict diagnostic group (Fisher’s exact p=0.067) but indicated increased odds of diminished exploration or activity in SZ (odds ratio=2.57, p=0.047). General amotivation differed across clusters (F(2,89)=6.31, p=0.003) due to significantly elevated scores in the low exploration and low activity clusters versus the high performance cluster. Evaluation of the diagnostic group by cluster assignment interaction effect for amotivation (F(2,86)=3.12, p=0.062) revealed significantly higher scores in SZ versus HC within the low exploration and high performance clusters, but not the low activity cluster. Evaluation of the interaction effect for community functioning (F(2,86)=4.86, p=0.007) revealed significantly lower scores in SZ versus HC within all clusters, with the discrepancy increasing from high performance to low activity to low exploration. Discussion: Multidimensional characterization of IM stands to provide valuable insights into motivation and functioning deficits in schizophrenia that behaviourally manifest differently across individuals. Impairment in IM-driven behaviour may be substantially detrimental particularly for individuals with schizophrenia, as SZ participants demonstrated clinically observable deficits even compared to withincluster HC counterparts. The current lack of objective standards to measure IM underscores the benefit of behaviour-based characterization. Further, as IM has been deemed a valuable psychosocial intervention target in schizophrenia, multidimensional behavioural phenotyping may help guide personalized therapy by differentiating between IM impairments demanding amelioration versus unimpaired tendencies that may be leveraged to facilitate remediation. [ABSTRACT FROM AUTHOR]

Background Few studies have sought to test the impact of psychosocial interventions on functional impairments in adolescents and young adults at clinical high risk (CHR) for psychosis. Moreover, reliable implementation of psychosocial interventions is costly, requiring years of advanced education and specialized training to adequately implement. Cognitive-Behavioral Social Skills Training (CBSST) combines elements of Cognitive Behavior Therapy with Social Skills Training, two evidence-based treatments for schizophrenia. In the current study, an existing CBSST manual was adapted to make content more appropriate for CHR age range and illness severity. The adapted manual was disseminated and implemented across 3 sites. Key changes to the published manual included a focus on normalization and destigmatization of attenuated psychotic symptoms, as well as examples and role plays that are appropriate for a young CHR sample. The aim of the current paper is to describe the manual modifications and present preliminary data demonstrating the success of training and supervision methods in this multi-site randomized controlled trial of CBSST in CHR youth. Case vignettes will demonstrate how CBSST techniques uniquely target functional impairments characteristic of emerging psychosis. Methods Subjects were eligible if they met criteria for a prodromal syndrome measured by the Scale of Prodromal Syndromes, demonstrated a mild impairment in social or role functioning, and were between the ages of 12–30. Facilitators included bachelor's level or above clinicians and trainees. Facilitator training on CBSST techniques was completed through a combination of in-person trainings and standardized training tapes. All sessions were audio recorded by facilitators. A random selection of recordings were systematically assessed by 2 raters, blinded to all participant data and tape selection procedure. Recordings were rated for CBT fidelity using the Cognitive Therapy Rating Scale for Psychosis (CTS-Psy) and the SST fidelity using the Social Skills Training Fidelity Scale. Recordings and ratings were used in weekly videoconference supervision to iteratively introduce technical modifications between sessions, address procedural errors, and provide facilitators with written feedback to improve fidelity. Weekly supervision served as a platform to discuss treatment manual revisions and effective strategies to engage youth in CBSST techniques. Results Fourteen audio recordings were evaluated per site. CTS-Psy and SST overall fidelity ratings were consistent across sites ([meanSD] Site 1=43.6 5.2, Site 2=42.63.0, and Site 3=41.92.8). There were no site differences on total general skill (Site 1=22.6 2.3, Site 2=20.71.8, and Site 3=21.32.1) nor CBSST technical skill (Site 1=20.93.4, Site 2=21.92.5, and Site 3=20.62.1) ratings. Discussion Overall fidelity ratings were above the "adequate" range (>30). Thus, quantitatively, a high level of fidelity was achieved through this model of training and supervision. Qualitatively, case vignettes yield anecdotal evidence that CBSST provides a unique set of techniques, easily administered by bachelor's level or above providers, that target functional impairments specific to CHR youth. Taken together, these results provide preliminary evidence that CBSST can be reliably implemented with high fidelity and low cost with target engagement of functional impairment in CHR youth. [ABSTRACT FROM AUTHOR]

Background Social functioning impairment is a core predictor of outcome in psychosis and a main target for interventions. Assessments reflecting social reality are thus essential. After the 2004 advent of Facebook, social networking platforms have become integral to young peoples' social life and yet it is unclear whether this is being assessed. The aim of this systematic review is to examine the inclusion of social media activity in measures of social functioning in psychosis and ultra-high-risk for psychosis. Methods Design: Systematic review. Data sources: Epistemonikos, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effect (DARE), MEDLINE, EMBASE and PsycINFO. Eligibility criteria for study selection: Empirical study published in English language in peer reviewed journals, with a sample meeting criteria (DSM/ICD) for a psychotic disorder or ultra-high risk for psychosis, and including a measure of social functioning. Papers published between January 2004 and April 2018 were included. Data extraction: The electronic search resulted in 10,575 distinct articles. Full-text evaluation was conducted on 690 articles of which 573 articles met inclusion criteria. Results 58 social functioning measures were identified. With some exceptions, reports on reliability and validity were scarce and only one measures integrated social media social activity. Discussion The ecological validity of social functioning measures is challenged by the lack of assessment of social media activity as it fails to reflect an important aspect of the current social reality of persons with psychosis. Measures should be revised to include social media activity and thus avoid the clinical consequences of inadequate assessment of social functioning. [ABSTRACT FROM AUTHOR]

Background: The so-called “novel psychoactive substances” (NPS) or “legal highs” have been highly used by adolescent and young population in the last decade, reaching a level at which they became a challenge for policy makers and public health [1]. Drugs like synthetic cannabinoids, synthetic cathinones, Salvia divinorum, phenylethylamines, synthetic cocaine substitutes and Mitragyna speciosa have been included in the NPS category and patients diagnosed with bipolar disorder, personality disorders or schizophrenia and related disorders were the most frequently associated disorders with NPD use (between 11.6 and 23.1%) [2]. Case reports of the NPS-induced relapses among patients with schizophrenia exist, and a toxicology screening rarely detect these substances [3]. The impact of NPS in the prodromal phase of schizophrenia is associated with several important questions, like “is there a common predisposition for both NPS abuse and schizophrenia spectrum disorders?”, or “how can the early treatment of the NPS abuse may interfere with the risk for the development of schizophrenia?”. Methods: A number of three patients who presented NPS use and attenuated psychotic syndrome (according to the DSM-5 criteria for conditions for further study) were monitored for 3 months during their detox treatment and after that period, during which they received a maintenance treatment with moodstabilizers (carbamazepine 600–900 mg daily or sodium valproate 500– 1000 mg daily) and naltrexone (50 mg daily). Two patients accepted also lowdose antipsychotic treatment with olanzapine (5 mg/daily). Psychological counselling was offered and accepted by all three patients. These patients were evaluated every 4 weeks using Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Clinical Global Impressions – Severity (CGI-S), and Inventary for Drug Taking Situations (IDTS). No other axis I or III diagnoses were detected in any of these patients. However, two patients presented features of cluster A personality disorders, without reaching the threshold for a clear-cut axis II diagnosis. Results: All three patients reached the week 12 visit, and they presented improvements in the PANSS scores, including the patient who refused antipsychotic treatment (mean PANSS reduction was 23.7 points compared to baseline). GAF increased with 29.9 points, and CGI-S decreased with 1.9 points. IDTS had a more fluctuating course, with final values being modestly reduced to baseline (-10.7, p=0.127). One patient remained abstinent from NPS for 2 months, while the other two admitted a continuation of the drugs use during the 3 months of their monitoring period. No discontinuation of the treatment was reported during to the low tolerability. Discussion: The initiation of pharmacological treatment and psychological counselling could improve the evolution of patients diagnosed with both NPS abuse and attenuated psychotic syndrome, as reflected at least by the PANSS scores, even if patients did not significantly improve their drug consumption. [ABSTRACT FROM AUTHOR]

Background: The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine is shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it may have therapeutic effects on negative symptoms. The present study presents a pilot prospective research study evaluating the efficacy of combining clozapine and sublingual oxytocin for the reduction of positive and negative symptoms. Methods: Prospective research study evaluated 25 treatment resistant schizophrenic patients who were admitted to the persistent psychotic disorder unit at a private hospital, with an average treatment duration of 2.9 months with a range between 1 and 9 months. All have been followed as outpatient for up to 30 months after discharge. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 25 patients after they had failed to improve in three different trials of other antipsychotic medications. Sublingual oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 25 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to a history of intranasal substance use in all the patients, oxytocin was administered sublingual to ensure adequate and less variable absorption of the neuropeptide. Results: A time-series analysis demonstrated a significant decrease in PANSS scores across admission, stabilization of clozapine and stabilization of oxytocin (p <.02) with the overall average PANSS score on admission was 102; after stabilization on clozapine, the average score decreased to 68. After administration oxytocin (8 weeks) the average score decreased further to 47 and improved PANSS score were not related to serum clozapine levels. Clinical and family notes indicated clinically meaningful improvements in affect, eye contact, and ability to socialize. These gains have been sustained over the full range of our observations. Families self-reported an increased ability to participate in social roles and activities. Discussion: The combined effect extends the current research of augmenting sublingual oxytocin and clozapine for individuals with previously treatment-resistant symptoms. Though each patient benefitted from clozapine alone, negative symptoms persisted. Patients, their families, and treatment program staff all observed a significant reduction in the patients’ anxiety and an improvement in the patients’ relatedness. While this case series cannot establish that oxytocin is responsible for the clinical improvements seen here, it does suggest that it may improve negative symptoms and social functioning in patients with treatment-resistant schizophrenia showing incomplete improvement with clozapine alone. The present study suggests the need for future research to explore the possibility that oxytocin can mitigate the negative symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Compassionate imagery may be one method of targeting the negative beliefs about the self and others that paranoid thoughts build upon. This talk presents two interventionist-causal studies testing this hypothesis, one targeting compassion for the self and one targeting compassion for others. These studies form part of the programme of work testing the manipulation of putative causal factors in paranoia, in individuals from the general population scoring highly for current paranoid ideation. Methods: Two hundred such individuals were recruited. The studies used a randomised controlled experimental design, with embedded tests for mediation. Study one targeted self-compassion via creation of a compassionate coach image. Study two targeted compassion for others via loving kindness meditation. Individuals repeatedly entered neutral virtual reality social environments and changes in compassion and paranoia were assessed. Results: Study one showed that, in comparison to the control group, those who practised compassionate coach imagery significantly increased in self-compassion (group difference=2.12, C.I.=1.57;2.67, p=<0.0001, d=1.4) and decreased in paranoia (group difference=-1.73, C.I.=-2.48;- 0.98, p=<0.0001, d=0.8). Mediation analysis indicated that change in self-compassion explained 57% of the change in paranoia. Study two showed that in comparison to the control group, those who practised loving kindness meditation significantly increased their compassion for others (group difference=3.26, 95% C.I.: 2.72;3.80, p=<0.0001, d=1.7), and decreased their paranoia (group difference=-1.70, C.I.=-2.51;-0.89, p=<0.0001, d=0.8). Change in compassion for others explained 63% of the change in paranoia. Discussion: Together, the studies suggest that targeting negative beliefs about the self and others using compassionate imagery causes reductions in paranoia, which may have benefits in clinical populations. [ABSTRACT FROM AUTHOR]

Background: Clozapine possesses unique efficacy profile in treatment resistant schizophrenia but is associated with neutropenia and agranulocytosis, in respectively, 3% and 0.7% of exposed patients. Granulocyte colony-stimulating factor (G-CSF) has been used to allow clozapine continuation or rechallenge in such situation (1,2). Methods: We aim to describe the use of G-CSF to maintain clozapine despite neutropenia or agranulocytosis in treatment resistant schizophrenia patients in Quebec province, Canada. A national clozapine hematological monitoring database was consulted to identify all patients who have had red event (neutrophil count < 1,5 threshold) since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who have received at least one dose of G-CSF while been exposed to clozapine All patients with an active cancer diagnosis while taking clozapine and G-CSF were excluded. A group of pharmacists specialized in psychiatry in Quebec was also contacted to ensure selecting all cases in the province. In additional to demographic data and clozapine and G-CSF details, Clinical Global Impression severity scale (CGI-S) was used to evaluate psychopathology severity during four critical turning points: before and after clozapine introduction, after agranulocytosis episode and after clozapine rechallenge. All data were collected retrospectively, using patient’s medical files, from January to July 2019. Results: Eight (8) patients (5 males, 3 females), Caucasian, mean age 48 years old, with clozapine median exposition of 4.8 years, were identified. In 7/8 of those, G-CSF was used according to an “as required strategy”, i.e., whenever the patient’s neutrophil count dropped below a pre-determined threshold, varying according to patient between 0,8 à 1,5. In the other patient, a 3-weekly doses were preventively administered. Despite this, a mean number of 4 red events (ranging from 1 to 10 events) were subsequently observed in those patients, leading to clozapine cessation in 4/8 patients. One other patient responded to G-CSF but the clinical team felt uncomfortable to maintain clozapine in such circumstances. No complication (infection for instance) due to low neutrophil counts was observed nor any significant side effect related to G-CSF. However, in all these cases, while clozapine treatment was associated with clinically significant improvement of psychopathology (mean CGI-S decreased from 5.5 to 3.4), clozapine cessation led to an important psychotic deterioration (mean CGI-S of 6.2) at follow up. Fortunately, in patients successfully rechallenged (3/8), a strong clinical improvement was observed, with return to previous response level observed. Discussion: To our knowledge, this is the largest case series of clozapine rechallenge using G-CSF and adds to the 39 already described cases in which G-CSF was concomitantly used with clozapine (1,2). While an “as required” strategy was mainly used here, a different prophylactic G-CSF use may have led to higher rates of clozapine maintenance, despite red codes, which provides the impetus for further studies. [ABSTRACT FROM AUTHOR]

Background Prenatal exposure to the viral mimic polyinosinic-polycytidilic acid (poly-I:C) has been shown to produce a wide spectrum of brain and behavioral abnormalities phenotypic of schizophrenia. We showed that prenatal poly-I:C led to increasingly widespread volumetric abnormalities that preceded the emergence of behavioral deficits, and that an ultra-low dose of risperidone (RIS) given to male offspring prior to "symptom" emergence (on PNDs 34–47), prevented both behavioral and structural abnormalities. Recently, we established a new model in which poly-I:C is administered to the nursing dams on PND4. This manipulation leads in the offspring to sexually dimorphic behavioral phenotypes in adulthood, with male but not female offspring exhibiting SCZ-like cognitive inflexibility (manifested in persistent latent inhibition [LI] and impaired reversal), and female but not male offspring exhibiting affective/hedonic deficit (manifested in increased immobility in the forced swim test [FST] and decreased saccharine preference), recapitulating the known sex bias in these disorders. These behavioral deficits are preceded by structural brain deterioration. Here, we tested whether adolescent RIS would be effective in preventing the sex-specific behavioral deficits induced by lactational poly-I:C as it is effective in preventing behavioral deficits induced by gestational poly-I:C. Methods PolyI:C (4mg/kg) or saline, was injected to pregnant dams on GD 15 or to lactating dams on PND 4. Female offspring that underwent gestational exposure (results in males were already published) and offspring of both sexes that underwent lactational exposure, were injected daily with RIS (0.045 mg/kg) at adolescence (PNDs 34–47). At adulthood all the offspring underwent in-vivo structural imaging and behavioral testing - LI and AIA in prenatal poly-I:C females and in lactational poly-I:C males, and FST in lactational polyI:C females. Results Adult females prenatally exposed to poly-I:C had disrupted LI and excessive AIA, as well as enlarged lateral ventricles and smaller hippocampal, striatal and prefrontocortical volumes. In the lactational model, poly-I:C exposed males exhibited persistent LI and hypo-response to amphetamine, and poly-I:C-exposed females exhibited increased immobility in the FST and hyper-response to amphetamine. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes at PND 70 and enlargement of LV at PND 200. Risperidone prevented poly-I:C-induced brain abnormalities as well as the emergence of behavioral abnormalities in both the prenatal and the lactational models. Discussion Ultra-low dose of risperidone administered in adolescence is effective in preventing both structural and behavioral consequences in the gestational immune activation model, and in both sexes in the lactational immune activation model. These findings provide the first evidence showing the efficacy of the same early intervention in preventing the emergence of distinct behavioral phenotypes caused by different early insults in the two sexes. Notably, the behavioral phenotypes are considered to model positive symptoms (disrupted LI and hyper-response to amphetamine, in females prenatally exposed to poly-I:C), negative/cognitive symptoms (persistent LI and hypo-response to amphetamine, in males lactationally exposed to poly-I:C), and depressive symptoms (increased immobility in FST in females lactationally exposed to poly-I:C). We conclude that the neurodevelopmentally compromised brain is remarkably plastic until "symptom" emergence, and that intervention during this pre-symptomatic vulnerability window is trans-risk factors and trans-diagnostic. [ABSTRACT FROM AUTHOR]

Background About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment. Moreover, as a robust clinical response is evident in only about half of patients treated with clozapine, the common practice is to augment the compound with another antipsychotic compound. However, little is known about the nature of this augmentation and the outcome in real-world setting. In this study, we aimed to explore in a real-world database, the details of clozapine use in patients with schizophrenia and the use of augmentation with other compounds as well as to explore the outcome of this augmentation in relation to physical health, medical care utilization, and mortality. Methods A retrospective cohort study of "Clalit Health Services" electronic records. People diagnosed with schizophrenia (F.20 ICD 10 code) and had at least one prescription filled for clozapine were followed up between 2012 and 2014. Results of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. Of them, 60% had polypharmacotherapy with another antipsychotic compound or lithium. The most prevalent augmentation was with sulpride (28%), perphenazine (17%) and zuclopenthixole (14.3%). Levels of physical comorbidity (metabolic and cardiovascular) were similar among groups (clozapine monotherapy vs. augmentation). However, polytherapy was associated with HR of 2.1 for mortality during the follow-up period. High mortality rate, during follow-up, was associated with haloperidol augmentation (12%) and sulpride (11.2%). Patients with augmentation were more referred to general emergency department and hospitalization while using similar rate of primary medical services as patients with clozapine monotherapy. Discussion Clozapine is under-utilized in Israel and data suggests that when treatment is given it is not optimized as reflected by high rates of polytherapy. This real-world practice is associated with increased mortality and higher use of tertiary medical service although patients had similar levels of metabolic and cardiovascular morbidity and similar primary medical service utilization rate. This data suggests that considering augmentation of clozapine with another antipsychotic compound should be done cautiously and after careful consideration of clozapine optimization. [ABSTRACT FROM AUTHOR]

Prior studies using exploratory factor analysis provide evidence that negative symptoms are best conceptualized as 2 dimensions reflecting diminished motivation and expression. However, the 2-dimensional model has yet to be evaluated using more complex mathematical techniques capable of testing structure. In the current study, network analysis was applied to evaluate the latent structure of negative symptoms using a community-detection algorithm. Two studies were conducted that included outpatients with schizophrenia (SZ; Study 1: n = 201; Study 2: n = 912) who were rated on the Brief Negative Symptom Scale (BNSS). In both studies, network analysis indicated that the 13 BNSS items divided into 6 negative symptom domains consisting of anhedonia, avolition, asociality, blunted affect, alogia, and lack of normal distress. Separation of these domains was statistically significant with reference to a null model of randomized networks. There has been a recent trend toward conceptualizing the latent structure of negative symptoms in relation to 2 distinct dimensions reflecting diminished expression and motivation. However, the current results obtained using network analysis suggest that the 2-dimensional conceptualization is not complex enough to capture the nature of the negative symptom construct. Similar to recent confirmatory factor analysis studies, network analysis revealed that the latent structure of negative symptom is best conceptualized in relation to the 5 domains identified in the 2005 National Institute of Mental Health consensus development conference (anhedonia, avolition, asociality, blunted affect, and alogia) and potentially a sixth domain consisting of lack of normal distress. Findings have implications for identifying pathophysiological mechanisms and targeted treatments. [ABSTRACT FROM AUTHOR]

Elucidating schizotypal traits is important if we are to understand the various manifestations of psychosis spectrum liability and to reliably identify individuals at high risk for psychosis. The present study examined the network structures of (1) 9 schizotypal personality domains and (2) 74 individual schizotypal items, and (3) explored whether networks differed across gender and culture (North America vs China). The study was conducted in a sample of 27001 participants from 12 countries and 21 sites (M age = 22.12; SD = 6.28; 37.5% males). The Schizotypal Personality Questionnaire (SPQ) was used to assess 74 self-report items aggregated in 9 domains. We used network models to estimate conditional dependence relations among variables. In the domain-level network, schizotypal traits were strongly interconnected. Predictability (explained variance of each node) ranged from 31% (odd/magical beliefs) to 55% (constricted affect), with a mean of 43.7%. In the item-level network, variables showed relations both within and across domains, although within-domain associations were generally stronger. The average predictability of SPQ items was 27.8%. The network structures of men and women were similar (r =.74), node centrality was similar across networks (r =.90), as was connectivity (195.59 and 199.70, respectively). North American and Chinese participants networks showed lower similarity in terms of structure (r = 0.44), node centrality (r = 0.56), and connectivity (180.35 and 153.97, respectively). In sum, the present article points to the value of conceptualizing schizotypal personality as a complex system of interacting cognitive, emotional, and affective characteristics. [ABSTRACT FROM AUTHOR]