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Objective: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive–compulsive‐related disorders in a normative twin population. Method: Four hundred and ninety‐six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology—ICE FALCON—to determine whether there was evidence consistent with ‘causal’ relationships between HA and other symptoms by fitting and comparing model estimates. Results: Estimates were consistent with higher levels of obsessing (‘unwanted thoughts’) (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). Conclusion: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA‐related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors. [ABSTRACT FROM AUTHOR]

Schizophrenia is a debilitating disorder that typically begins in adolescence and is characterized by perceptual abnormalities, delusions, cognitive and behavioural disturbances and functional impairments. While current treatments can be effective, they are often insufficient to alleviate the full range of symptoms. Schizophrenia is associated with structural brain abnormalities including grey and white matter volume loss and impaired connectivity. Recent findings suggest these abnormalities follow a neuroprogressive course in the earliest stages of the illness, which may be associated with episodes of acute relapse. Neuroinflammation has been proposed as a potential mechanism underlying these brain changes, with evidence of increased density and activation of microglia, immune cells resident in the brain, at various stages of the illness. We review evidence for microglial dysfunction in schizophrenia from both neuroimaging and neuropathological data, with a specific focus on studies examining microglial activation in relation to the pathology of grey and white matter. The studies available indicate that the link between microglial dysfunction and brain change in schizophrenia remains an intriguing hypothesis worthy of further examination. Future studies in schizophrenia should: (i) use multimodal imaging to clarify this association by mapping brain changes longitudinally across illness stages in relation to microglial activation; (ii) clarify the nature of microglial dysfunction with markers specific to activation states and phenotypes; (iii) examine the role of microglia and neurons with reference to their overlapping roles in neuroinflammatory pathways; and (iv) examine the impact of novel immunomodulatory treatments on brain structure in schizophrenia. [ABSTRACT FROM AUTHOR]

Aim An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13-24-year-olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post-pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder. Method This paper describes the study methodology, which involves a longitudinal cohort design implemented within four headspace youth mental health services in Australia. Participants are young people aged 12-25 years who have sought help at headspace and consented to complete a comprehensive assessment of clinical state and psychosocial risk factors. A total of 802 young people (66% female) completed baseline assessments. Annual follow-up assessments have commenced. Conclusions The results of this study may have implications for the way mental disorders are diagnosed and treated, and progress our understanding of the pathophysiologies of complex mental disorders by identifying genetic or psychosocial markers of illness stage or progression. [ABSTRACT FROM AUTHOR]

Objective It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. Method We conducted meta-analyses of studies comparing familial-high risk ( FHR) or ultra-high risk ( UHR; n = 2113) and healthy controls ( n = 1748) in youth studies in which the mean age was between 15 and 29. Results Compared with controls, high risk subjects were impaired in each domain in both UHR ( d = 0.34-0.71) and FHR ( d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis ( I2 = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains ( d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. Conclusion Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits. [ABSTRACT FROM AUTHOR]

Memory-guided decision making is dynamic and context-dependent, even though many studies describe an enhancement of the P3 for recognized items in memory tasks ('old-new effect'). This study utilized a delay-dependent working memory task during which decision making could be optimized by focusing attention on detected changes instead of recognized similarities. Mean P3 amplitude and delta activity were analyzed from participants who classified probe stimuli as identical or modified. The P3 amplitudes were larger for modified than for identical probes, even when the probe occurred 4,000 ms after the primary stimulus. Enhanced single-trial amplitude, trial-by-trial consistency, and frontoparietal phase coherence of delta activity contributed to the larger P3 for the modified probe. Thus, context-dependent attentional resource allocation supporting memory-guided decisions might explain the enhancement of the P3 for specific probe types. [ABSTRACT FROM AUTHOR]

Bora E, Yücel M, Pantelis C, Berk M. Meta-analytic review of neurocognition in bipolar II disorder. The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls. Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls. Individuals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains. Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait-marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high-risk (HR) for psychosis and first-degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait-marker. [ABSTRACT FROM AUTHOR]

Objective: Evidence related to overlapping clinical and genetic risk factors in schizophrenia and bipolar disorder (BD) have raised concerns about the validity of ‘Kraepelinian dichotomy’. As controversies mainly arise in mixed psychoses that occupy the intermediate zone between schizophrenia and BD, investigating neurobiological markers of mixed psychoses may be relevant to understanding the nature of psychotic disorders. Method: In this article, we review studies comparing magnetic resonance imaging, neuropsychological and electrophysiological findings in mixed psychoses with each other, as well as with more prototypical cases of schizophrenia and BD. Results: The evidence reviewed suggests that mixed psychoses may be associated with different genetic and neurobiological markers compared with prototypical forms of schizophrenia and BD. Conclusion: These findings may be compatible with more sophisticated versions of dimensional and continuum models or, alternatively, they may suggest that there is an intermediate third category between prototypical schizophrenia and BD. [ABSTRACT FROM AUTHOR]

Objective: Anterior cingulate cortex (ACC) abnormalities are commonly reported in studies of patients with bipolar disorder (BD), but it is unclear whether these precede or follow illness onset. We investigated the evidence for early neurodevelopmental anomalies in the ACC and adjacent paracingulate cortex (PaC) of BD patients by studying cortical folding patterns of the region. Method: Magnetic resonance images were acquired from 54 BD patients and 116 healthy controls. Cortical folding patterns were assessed by classifying the incidence of the paracingulate sulcus (PCS) and interruptions in the course of the cingulate sulcus (CS). Results: Patients were significantly less likely to show a PCS bilaterally. There were no differences in the frequency of CS interruptions. Conclusion: The bilateral reduction observed in our patient sample implicates aberrant pre- or peri-natal developmental processes. To our knowledge, this is the first in vivo evidence for early neurodevelopmental anomaly of the ACC/PaC region in BD. [ABSTRACT FROM AUTHOR]

Objective: Functional abnormalities of the dorsal anterior cingulate (dAC) region have been emphasized in schizophrenia, particularly in relation to cognitive deficits. In this study, we sought to further evaluate the notion of dAC hypofunction in chronic schizophrenia patients using a cognitive task specifically designed to activate this region, enabling both group and single-subject level analyses. Method: Twelve male schizophrenia patients and 14 male healthy subjects were studied with functional magnetic resonance imaging (fMRI) and the multi-source interference task (MSIT). Patients and healthy subjects were matched for age, gender, education, task performance and gross surface morphology of the AC region. fMRI analyses were conducted at the group and single-subject levels using stringent whole-brain activation thresholds. Results: Multi-source interference task performance was associated with large and significant activation of the dAC and supplementary motor area (SMA) in patients and healthy subjects. Standard comparison of the two groups indicated that the patients were comparable with healthy subjects in their dAC activation, but had a small cluster of greater SMA activation, while single-subject analyses identified minimal differences in the magnitude or spatial dispersion of dAC activation between the groups. Conclusion: These findings challenge existing notions of impaired dAC activation in chronic schizophrenia and suggest that the functional pathophysiology of this medial-wall region should be considered beyond straightforward models of hypoactivation. [ABSTRACT FROM AUTHOR]

Objective: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. Method: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. Results: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. Conclusion: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. Method: Totally 340 clinical MRI reports [Controls (n =98), first-episode psychoses (n =152), chronic schizophrenia (n =90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). Results: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. Conclusion: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning. [ABSTRACT FROM AUTHOR]

Bipolar disorder follows a staged trajectory in which persistence of illness is associated with a number of clinical features such as progressive shortening of the inter-episode interval and decreased probability of treatment response. This neuroprogressive clinical process is reflected by both progressive neuroanatomical changes and evidence of cognitive decline. The biochemical foundation of this process appears to incorporate changes in inflammatory cytokines, cortisone, neurotrophins and oxidative stress. There is a growing body of evidence to suggest that these markers may differ between the early and late stages of the disorder. The presence of a series of tangible targets raises the spectre of development of rational neuroprotective strategies, involving judicious use of current therapies and novel agents. Most of the currently used mood stabilisers share effects on oxidative stress and neurotrophins, while novel potentially neuroprotective agents are being developed. These developments need to be combined with service initiatives to maximise the opportunities for early diagnosis and intervention. [ABSTRACT FROM AUTHOR]

A fundamental shift in the design of clinical trials for psychotic disorders is desirable and feasible. Priority should be placed on evaluation of the efficacy of interventions targeting different phases of illness. A range of traditional therapeutic approaches needs to be augmented by an increased emphasis on the potential benefits of informational, e-health, behavioural and neuroprotective strategies. A new national clinical trials platform, based on headspace, the National Youth Mental Health Foundation, is outlined. It provides the opportunity for conducting large multisite clinical trials in young people with emerging major mental disorders. [ABSTRACT FROM AUTHOR]

Neuroimaging studies of individuals at risk of psychosis have the potential to identify markers predictive of illness onset and features that progress with transition. To date, reduced brain volumes have shown weak predictive value for onset of psychotic illness. All published longitudinal studies of the transition to psychosis show progressive brain changes that are not seen in at-risk individuals who do not develop the disorder. Although the cause of these changes is unclear, they challenge the conventional neurodevelopmental model of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Evidence shows impaired theory of mind (ToM) in patients with bipolar disorder (BD), yet research examining its cognitive and affective components simultaneously is sparse. Moreover, recognition of socially competitive 'fortune of others' emotions (e.g. envy/gloat) may be related to ToM, but has not been assessed in BD. Finally, if and how ToM and 'fortune of others' emotions relate to affective empathy in BD is currently unclear. This study aimed to address these points., Methods: 64 BD patients and 34 healthy controls completed the Yoni task, a visual task assessing first- and second-order cognitive and affective ToM as well as 'fortune of others' emotions. The Toronto Empathy Questionnaire was used to assess self-reported affective empathy., Results: Patients with BD showed no deficits in cognitive and affective ToM or recognition of 'fortune of others' emotions. The ability to infer 'fortune of others' emotions correlated with several ToM measures, indicating that these functions are part of the same system. Patients with BD reported similar levels of affective empathy to healthy controls, and this was not related to ToM or 'fortune of others' emotions, suggesting that affective empathy represents a separate social domain., Conclusions: These findings highlight areas of spared social functioning in BD, which may be utilized in therapeutic strategies., Practitioner Points: Our results suggest theory of mind and empathy may represent areas of potentially spared cognitive functioning in BD. As many BD patients have experienced adversity during developmental periods in which theory of mind and empathy develop, our findings suggest that these abilities may be markers of resilience in the disorder. Our findings are important for the formulation of therapeutic interventions for BD, which may include considering practical ways that a patients' knowledge of intact ToM and empathy could be utilized to reduce self-stigma and promote self-efficacy, improved well-being and functioning., (© 2021 The British Psychological Society.)

Objective: Psychosis spectrum disorders are associated with cerebral changes, but the prognostic value and clinical utility of these findings are unclear. Here, we applied a multivariate statistical model to examine the predictive accuracy of global white matter fractional anisotropy (FA) for transition to psychosis in individuals at ultra-high risk for psychosis (UHR)., Methods: 110 UHR individuals underwent 3 Tesla diffusion-weighted imaging and clinical assessments at baseline, and after 6 and 12 months. Using logistic regression, we examined the reliability of global FA at baseline as a predictor for psychosis transition after 12 months. We tested the predictive accuracy, sensitivity and specificity of global FA in a multivariate prediction model accounting for potential confounders to FA (head motion in scanner, age, gender, antipsychotic medication, parental socioeconomic status and activity level). In secondary analyses, we tested FA as a predictor of clinical symptoms and functional level using multivariate linear regression., Results: Ten UHR individuals had transitioned to psychosis after 12 months (9%). The model reliably predicted transition at 12 months (χ 2  = 17.595, p = 0.040), accounted for 15-33% of the variance in transition outcome with a sensitivity of 0.70, a specificity of 0.88 and AUC of 0.87. Global FA predicted level of UHR symptoms (R 2  = 0.055, F = 6.084, p = 0.016) and functional level (R 2  = 0.040, F = 4.57, p = 0.036) at 6 months, but not at 12 months., Conclusion: Global FA provided prognostic information on clinical outcome and symptom course of UHR individuals. Our findings suggest that the application of prediction models including neuroimaging data can inform clinical management on risk for psychosis transition., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Executive Function (EF) and Effortful Control (EC) have traditionally been viewed as distinct constructs related to cognition and temperament during development. More recently, EF and EC have been implicated in top-down self-regulation - the goal-directed control of cognition, emotion, and behavior. We propose that executive attention, a limited-capacity attentional resource subserving goal-directed cognition and behavior, is the common cognitive mechanism underlying the self-regulatory capacities captured by EF and EC. We addressed three related questions: (a) Do behavioral ratings of EF and EC represent the same self-regulation construct? (b) Is this self-regulation construct explained by a common executive attention factor as measured by performance on cognitive tasks? and (c) Does the executive attention factor explain additional variance in attention deficit hyperactivity disorder (ADHD) problems to behavioral ratings of self-regulation? Measures of performance on complex span, general intelligence, and response inhibition tasks were obtained from 136 preadolescent children (M = 11 years, 10 months, SD = 8 months), along with self- and parent-reported EC, and parent-reported EF, and ADHD problems. Results from structural equation modeling demonstrated that behavioral ratings of EF and EC measured the same self-regulation construct. Cognitive tasks measured a common executive attention factor that significantly explained 30% of the variance in behavioral ratings of self-regulation. Executive attention failed to significantly explain additional variance in ADHD problems beyond that explained by behavioral ratings of self-regulation. These findings raise questions about the utility of task-based cognitive measures in research and clinical assessment of self-regulation and psychopathology in developmental samples., (© 2019 John Wiley & Sons Ltd.)

Aim: Up to half of patients with borderline personality disorder report auditory verbal hallucinations that are phenomenologically indistinguishable from those in schizophrenia, occur early in the course of the disorder, and are enduring, distressing and disabling. In clinical practice, this symptom is widely assumed to be unresponsive to treatment with antipsychotic medication and early intervention is rarely offered. The Verbal Experiences Response in Borderline personality disorder to Aripiprazole TrIal Medication (VERBATIM) study aims to be the first controlled trial to investigate the effectiveness of conventional pharmacotherapy for this symptom in this patient group., Method: VERBATIM is a 12-week, triple-blind, single-centre, parallel groups randomised controlled trial, with a 27-week follow-up period. Participants between the ages of 15 and 25 years receive either aripiprazole or placebo daily, commencing at 2 mg and increasing to 10 mg by day 15. Further dose escalations (up to 30 mg) may occur, as clinically indicated. This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616001192471 on 30/08/2016., Results: The primary outcome is severity of auditory verbal hallucinations assessed using the Psychotic Symptom Rating Scale. Secondary outcomes include the severity of general psychopathology, borderline personality pathology, social and occupational functioning and change in brain resting state connectivity. The primary endpoint is week 12 and secondary endpoint is week 39., Conclusion: The results will inform treatment decisions for individuals with borderline personality disorder who present with auditory verbal hallucinations., (© 2019 John Wiley & Sons Australia, Ltd.)

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes., Aim: The primary aim of the study is, in a population of young people with first-episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence-based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24-months follow-up., Methods: Our single-blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2-year period in 180 remitted first-episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow-up., Results: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017., Conclusion: This study will provide evidence as to whether an antipsychotic dose-reduction recovery treatment leads to improved functioning and safer outcomes in first-episode psychosis patients. In addition, it will be the first-controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population., (© 2018 John Wiley & Sons Australia, Ltd.)

Aim: Clinical staging models offer a useful framework for understanding illness trajectories, where individuals are located on a continuum of illness progression from stage 0 (at-risk but asymptomatic) to stage 4 (end-stage disease). Importantly, clinical staging allows investigation of risk factors for illness progression with the potential to target trans-diagnostic mechanisms at an early stage, especially in help-seeking youth who often present with sub-threshold syndromes. While depressive symptoms, rumination and sleep-wake disturbances may worsen syndrome outcomes, the role of these related phenomena has yet to be examined as risk factors for trans-diagnostic illness progression in at-risk youth., Methods: This study is a prospective follow-up of 248 individuals aged 12 to 25 years presenting to headspace services with sub-threshold syndromes (stage 1) classified under the clinical staging model to determine transition to threshold syndromes (stage 2). Factor analysis of depression, rumination and sleep-wake patterns was used to identify key dimensions and any associations between factors and transition to stage 2 at follow-up., Results: At 1 year, 9% of cases met criteria for stage 2 (n = 22). One of three identified factors, namely the factor reflecting the commonalities shared between rumination and sleep-wake disturbance, significantly differentiated cases that transitioned to stage 2 vs those that did not demonstrate transition. Items loading onto this factor, labelled Anergia, included depression severity and aspects of rumination and sleep-wake disturbance that were characterized as introceptive., Conclusions: Common dimensions between rumination and sleep-wake disturbance present a detectable trans-diagnostic marker of illness progression in youth, and may represent a target for early intervention., (© 2018 John Wiley & Sons Australia, Ltd.)

Aim: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented., Methods: This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans., Results: Ninety participants have been recruited and baseline characteristics are presented., Conclusions: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines., (© 2018 John Wiley & Sons Australia, Ltd.)

Aim: The Transitions Study was designed to establish a cohort of young people (12-25 years) seeking help for mental health problems, in order to longitudinally explore and refine a clinical staging model of the development and progression of mental disorders. This paper presents the baseline demographic and clinical characteristics of the cohort, particularly the nature and severity of psychopathology., Method: All eligible young people attending one of four headspace clinical services were invited to participate, and completed a battery of self-report and interviewer-administered measures of psychopathology and functional impairment at baseline, which will be repeated at the annual follow up., Results: Of 1615 eligible clients, 802 young people (66% women; mean age = 18.3 years) consented to participate and completed baseline assessments (participation rate = 50%). The severity of mental health problems varied, with 51% meeting the criteria for probable caseness related to generalized anxiety, 45% presenting with moderate to severe depressive symptoms and over a third experiencing subthreshold psychotic symptomatology. Disordered eating (32%) and problematic tobacco (56%), cannabis (30%) and alcohol (38%) use also affected a significant proportion. Overall, 39% of the cohort were classed as being functionally impaired at baseline., Conclusion: The Transitions Study recruited a heterogeneous cohort at baseline in relation to the nature and severity of mental health problems and levels of functional impairment. The variation in clinical presentations within the cohort, from mild, through moderate to severe levels of psychopathology and impairment, increases the likelihood of the Transitions Study ultimately being able to achieve its aims of empirically testing a clinical staging model for mental disorders., (© 2014 Wiley Publishing Asia Pty Ltd.)

While past twin studies indicate moderate levels of heritability of "obsessive-compulsive related" and anxiety disorder symptoms, no single study has reported such estimates in the same twin population nor examined potential genetic sex differences. We assessed symptoms of obsessive-compulsive disorder, body dysmorphic disorder, hoarding disorder, hypochondriasis, panic disorder, social phobia and generalized anxiety disorder in 2,495 adult twins (1,468 female). Prevalence estimates for the corresponding symptom measures were determined using empirically derived cut-off scores. Twin resemblance was assessed by Pearson correlations and biometrical model-fitting analyses, incorporating sex-specific effects, using OpenMx. Prevalence estimates ranged from 1.6% in the symptoms of generalized anxiety to 16.9% for social phobia. Female twins demonstrated significantly higher prevalence rates across all domains with the exception of obsessive-compulsive symptoms. Additive genetic factors accounted for a moderate proportion of the total liability to each symptom domain. Evidence suggesting qualitative genetic sex differences (i.e., distinct genetic influences between genders) was observed for body dysmorphic concern and panic symptoms, while quantitative differences were observed for hoarding and social phobia symptoms, indicating stronger heritability in females. Novel findings in this study include the observation of probable genetic sex differences in liability towards hoarding symptoms and dysmorphic concern, as well as the lack of such differences in hypochondriasis. The trend towards qualitative sex differences in panic symptoms has some intuitive appeal with regard to biological-experimental models of panic., (© 2014 Wiley Periodicals, Inc.)

Aim: The study aims to apply clinical staging to young people who present for mental health care; to describe the demographic features, patterns of psychological symptoms, disability correlates and clinical stages of those young people; and to report longitudinal estimates of progression from less to more severe stages., Methods: The study uses cross-sectional and longitudinal assessments of young people managed in specialized youth clinics. On the basis of clinical records, subjects were assigned to a specific clinical 'stage' (i.e. 'help-seeking', 'attenuated syndrome', 'discrete disorder' or 'persistent or recurrent illness')., Results: Young people (n = 209, mean age = 19.9 years (range = 12-30 years), 48% female) were selected from a broader cohort of n = 1483 subjects. Ten percent were assigned to the earliest 'help-seeking' stage, 54% to the 'attenuated syndrome' stage, 25% to the 'discrete disorder' stage and 11% to the later 'persistent or recurrent illness' stage. The interrater reliability of independent ratings at baseline was acceptable (κ = 0.71). Subjects assigned to the 'attenuated syndrome' stage reported symptom and disability scores that were similar to those assigned to later stages. Longitudinally (median = 48 weeks), transition to later clinical stages were 11% of the 'help-seeking', 19% of the 'attenuated syndrome' and 33% of the 'discrete disorder' groups., Conclusion: Among young people presenting for mental health care, most are clinically staged as having 'attenuated syndromes'. Despite access to specialized treatment, a significant number progress to more severe or persistent disorders., (© 2012 Wiley Publishing Asia Pty Ltd.)

Aims: The study aims to identify markers of vulnerability to obsessive-compulsive disorder (OCD) in an ultra-high risk sample of patients who developed psychosis., Methods: Three hundred and eleven patients at ultra-high risk for psychosis were examined at baseline and after a mean of 7.4 years follow-up. Patients who developed psychosis with OCD (PSY + OCD; n = 13) and psychosis without OCD (PSY - OCD; n = 45) were compared in terms of socio-demographic and clinical features., Results: PSY + OCD patients displayed greater severity of depression before and after conversion to PSY + OCD, and increased rates of depressive disorders before exhibiting PSY + OCD. However, they only displayed greater severity of anxiety and increased rates of non-OCD anxiety disorders after psychosis. Further, PSY + OCD patients were more likely to report a positive family history for anxiety disorders than PSY - OCD., Conclusion: Although depression and a family history of anxiety disorder may act as vulnerability markers for OCD in psychosis, the resulting anxiety may be a correlate or a consequence of PSY + OCD., (© 2012 Blackwell Publishing Asia Pty Ltd.)

Heroin addiction has been associated with impaired neuronal connectivity and cognitive deficits. One mechanism that potentially explains these findings is alterations in white matter connectivity secondary to chronic opiate use. However, few studies have quantitavely examined white matter deficits in opiate addiction (OA). Here, we investigated white matter microstructure in OA using diffusion tensor imaging (DTI). We performed voxel-wise analysis of fractional anisotropy (FA) in 24 participants with OA and 29 healthy controls. The OA group showed reduced FA in multiple pathways including the corpus callosum, thalamic radiation and inferior longitudinal fasciculus. This FA reduction was mainly the result of increased radial diffusivity (λ(⊥)), indicative of myelin pathology. Longer duration of OA was also associated with axonal diffusivity (λ(1)), most robustly in superior longitudinal fasciculi and right frontal white matter suggesting axonal injury in long-term users. Together, the findings indicate that chronic OA use has widespread and diverse effects on neuronal connectivity and function., (© 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.)

Aims: Addiction has been conceptualized as a shift from controlled experimentation to uncontrolled, compulsive patterns of use. Current neurobiological models of addiction emphasize changes within the brain's reward system, such that drugs of abuse 'hijack' this system and bias behaviour towards further drug use. While this model explains the involuntary nature of craving and the motivational drive to continue drug use, it does not explain fully why some addicted individuals are unable to control their drug use when faced with potentially disastrous consequences. In this review, we argue that such maladaptive and uncontrolled behaviour is underpinned by a failure of the brain's inhibitory control mechanisms., Design: Relevant neuroimaging, neuropsychological and clinical studies are reviewed, along with data from our own research., Findings: The current literature suggests that in addition to the brain's reward system, two frontal cortical regions (anterior cingulate and orbitofrontal cortices), critical in inhibitory control over reward-related behaviour, are dysfunctional in addicted individuals. These same regions have been implicated in other compulsive conditions characterized by deficits in inhibitory control over maladaptive behaviours, such as obsessive-compulsive disorder., Conclusions: We propose that in chronically addicted individuals, maladaptive behaviours and high relapse rates may be better conceptualized as being 'compulsive' in nature as a result of dysfunction within inhibitory brain circuitry, particularly during symptomatic states. This model may help to explain why some addicts lose control over their drug use, and engage in repetitive self-destructive patterns of drug-seeking and drug-taking that takes place at the expense of other important activities. This model may also have clinical utility, as it allows for the adoption of treatments effective in other disorders of inhibitory dysregulation.