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UNLABELLED: 22q11.2 deletion syndrome (22q11.2DS) is characterised by high rates of psychotic disorders and immune abnormalities. Blood-brain barrier (BBB) permeability is known to be a risk factor for schizophrenia and immune aberrations. OBJECTIVE: To evaluate the relationship between psychosis and BBB permeability in this population. METHODS: We examined two biomarkers for BBB permeability, s100β and neuron-specific enolase (NSE), in 22q11.2DS individuals with/without psychosis. The first cohort of this Israeli-Belgium study was comprised of 20 22q11.2DS adults (30.58 ± 9.42 years) afflicted with a psychotic disorder, another group of 69 non-psychotic 22q11.2DS adults (23.42 ± 8.36 years), and 58 healthy controls (26.39 ± 7.77 years). A second cohort was comprised of 18 non-psychotic 22q11.2DS Israeli children (5.83 ± 1.55 years) and 14 healthy controls (5.34 ± 1.43 years). NSE and s100β serum levels were detected in all participants. RESULTS: Both factors were elevated in adults with 22q11.2DS compared to healthy controls, specifically in the non-psychotic sub-group. In contrast, there were no significant differences in their levels between the two groups of the paediatric cohort. CONCLUSIONS: Increased BBB permeability seems to be a trait of 22q11.2DS that evolves sometime in early adulthood. Our findings are in line with previous reports on non-syndromic schizophrenia, and suggest potential novel neural pathways to psychosis in 22q11.2DS. ispartof: WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY vol:23 issue:6 pages:475-482 ispartof: location:England status: published

To compare the rates of schizophrenia among 1st and 2nd generation immigrants from two distinct backgrounds and across sequential periods of immigration.A 30-years retrospective cohort study (187,184 individuals) of 1st and 2nd generation East-African immigrants (EAIs) and former Soviet-Union immigrants (FSUIs) who migrated to Israel between 1980 and 2012. EAIs were further divided according to waves of immigration. Period prevalence was calculated between the years 2002-2012. Multivariate logistic regression models were used to examine the association between immigration-related factors and prevalence of schizophrenia (Native-Born Israelis serving as reference group).The prevalence of schizophrenia in 1st generation EAIs and FSUIs was 1.8% and 1.2%, respectively, compared to 1.0% among NBIs (p0.001). The prevalence of schizophrenia among 2nd generation EAIs and FSUIs was 1.3% and 0.8%, respectively, compared to 0.6% among NBIs (p0.001). Adjusted odds ratios for developing schizophrenia compared to NBIs were 1.6 (95%CI:1.4-1.8) and 2.1 (95%CI:1.6-2.7), among 1st and 2nd generation EAIs and 1.1 (95%CI:0.9-1.2) and 1.3 (95%CI:1.0-1.8) among 1st and 2nd generation FSUIs respectively. Among EAIs, we observed the highest rate of schizophrenia in the pioneer wave of immigrants with gradual decline across subsequent waves: 2.4%, 1.9% and 1.0% for the 1st, 2nd and 3rd waves of immigration, respectively (p0.001).The increased risk for developing schizophrenia among 2nd generation immigrants and among pioneer groups of immigrants emphasizes the importance of persistent investment in acculturation. Further studies elucidating the impact of country of origin and ethnic density on the risk for developing schizophrenia are warranted.

Schizophrenia patients have shorter life expectancy often owing to preventable physical illnesses and sub-optimal utilization of medical services. However, the association between service-utilization and mortality has not been explored.To assess whether medical service-utilization moderates the association between physical morbidity and premature mortality in a nation-wide cohort.A population representative database of the largest health provider in Israel was analyzed. All electronic health records of patients with schizophrenia diagnosis (ICD code F.20) (n = 24,679) were followed-up between 2012 and 2015, and compared to the general population (n = 2,232,804), in terms of metabolic and cardiovascular morbidity, all-cause mortality, primary medical and specialist health service-utilization and general hospitalizations.Schizophrenia was associated with increased mortality risk (adjusted hazard ratio (aHR) = 3.52, 95%CI 3.35-3.72). Most deaths were related to physical illnesses. Metabolic syndrome components, except chronic hypertension, were more prevalent among patients. They were referred more frequently to primary and less to secondary services (aHR = 1.05, 95%CI 1.04-1.06, aHR = 0.95, 95%CI 0.94-0.97, respectively), with higher hospitalization rates (0.23 ± 0.90 vs 0.10 ± 0.50 per year), and longer mean duration of hospitalization (2.02 ± 10.24 vs 0.68 ± 5.51 days, P 0.001). More contacts with primary care physicians or specialists positively moderated the association between mortality and metabolic disturbances in patients with schizophrenia; more contacts were associated with better outcomes.An association between premature mortality and metabolic syndrome was found among schizophrenia patients while utilization of primary/secondary medical services moderated the lethal effects of metabolic dysregulation. Increased integrative primary care and a national monitoring system are warranted to reduce mortality rate in this population.

Objectives: The effect of stimulants on anxiety domains has not been systematically studied. We assessed prospectively the impact of stimulant treatment in children with attention-deficit/hyperacti...

Objective: Use of risperidone in preschool-aged children is growing, with rising concerns of adverse metabolic consequences. Longitudinal data on risperidone-related weight gain in preschoolers are scarce. We aimed to evaluate changes in body mass index (BMI) that are associated with risperidone treatment in preschoolers. Method: We analyzed naturalistic, longitudinal data on 141 preschool children (112 boys, 29 girls) receiving psychiatric care. Mean patient age at baseline was 5.0 years (SD=0.8) and average follow-up period was 1.3 years (SD=0.8), with >8 mean BMI measurements per patient. We studied the effect of risperidone exposure ( n=78) on age-and-sex-standardized BMI (BMI Z-score) implementing mixed models with random subject intercepts to account for repeated measures, covarying for multiple confounders including demographics, stimulant treatment and psychiatric diagnoses. We employed similar models to study dose and duration effects. Results: Risperidone treatment was significantly associated with an increase in BMI (effect size of exposure=0.45 SD (SE=0.06), t (949)=7.7, pConclusion: Similar to older populations, risperidone treatment in preschoolers is associated with significant weight gain, with evidence for dose effects. Findings provide critical data that can inform clinicians.

The COVID-19 pandemic brought about a global crisis, with profound implications on public mental health. The current review focuses on the impact of the pandemic on the mental health of mothers and their infants during pregnancy and shortly after delivery. Literature shows that in similar disaster situations, mothers’ stress reaction and mental health have a critical impact on infant development. Research data on perinatal mental health during the current COVID-19 pandemic is reviewed in conjunction with studies on the relationship between maternal stress, infant development, and psychopathology. Recommendations for perinatal mental health enhancement are discussed and topics for future research suggested.

Introduction Depression and anxiety have been associated with type 2 diabetes mellitus and metabolic syndrome, major causes of cardiovascular morbidity and mortality. The effect of antidepressants in this association is unknown. This study aimed to examine the association between adherence to selective serotonin receptor inhibitors (SSRIs) and all-cause mortality among individuals with metabolic syndrome components (hypertension, obesity, and diabetes mellitus). Methods Data on 201 777 patients who were prescribed SSRIs during the years 2008–2011 were analyzed retrospectively. Adherence was measured using prescription purchase records. The moderating effect of SSRI and statin adherence on the association between metabolic syndrome load and mortality hazard risk (HR) during the study period were analyzed. The Cox-proportional hazard model adjusted to background variables was used to this end. Results During the study period, the maximal metabolic load was associated with mortality HR=1.89 (95% CI: 1.79–2) compared to participants without metabolic risk factors. A slight reduction in mortality HR was demonstrated among those with low and moderate SSRI adherence rates. Adherence to statins was negatively associated with the risk of mortality across all levels of adherence. A significant association (r=0.214, p Discussion While a high metabolic load is associated with a higher risk of mortality, adherence to SSRIs only partially moderated the risk of mortality, in contrast to the protective effect of statins. Adherence differences to statins and SSRIs among individuals prescribed both medications merit further investigation.

OBJECTIVE: Deliberate self-harm (DSH) is a major health concern among adolescents, and is often associated with the need for inpatient psychiatric hospitalization. The aim of this study was to identify clinical and demographic characteristics associated with DSH behavior among adolescents admitted to an acute psychiatric inpatient unit. METHOD: We retrospectively analyzed data from the electronic medical records of consecutive admittances to a single acute adolescent inpatient unit (N=703, mean age 15.2). We compared inpatients with DSH to inpatients without DSH, and further compared within DSH group based on the presence of suicidal intent. RESULTS: Compared to Non-DSH inpatients (N=497), youths admitted following DSH (N=206) were more likely to be female (OR=2.6, 95%CI 1.7–4), currently in depressive exacerbation (OR=2.4, 95%CI 1.6–3.6), with concurrent suicidal ideation (OR=3.9, 95%CI 2.5–5.9), and history of alcohol use (OR=5.6, 95%CI 3.2–9.5). Within DSH youths, no significant clinical differences were identified between those admitted following suicide attempt (N=102) compared to non-suicidal-self-injury (N=104), who were generally younger. CONCLUSIONS: Findings suggest that early detection and intervention of DSH and depressive crisis is warranted, regardless of the self-harm subtype.

Background Currently, postpartum depression (PPD) screening is mainly based on self-report symptom-based assessment, with lack of an objective, integrative tool which identifies women at increased risk, before the emergent of PPD. We developed and validated a machine learning-based PPD prediction model utilizing electronic health record (EHR) data, and identified novel PPD predictors. Methods A nationwide longitudinal cohort that included 214,359 births between January 2008 and December 2015, divided into model training and validation sets, was constructed utilizing Israel largest health maintenance organization's EHR-database. PPD was defined as new diagnosis of a depressive episode or antidepressant prescription within the first year postpartum. A gradient-boosted decision tree algorithm was applied to EHR-derived sociodemographic, clinical, and obstetric features. Results Among the birth cohort, 1.9% (n = 4104) met the case definition of new-onset PPD. In the validation set, the prediction model achieved an area under the curve (AUC) of 0.712 (95% confidence interval, 0.690-0.733), with a sensitivity of 0.349 and a specificity of 0.905 at the 90th percentile risk threshold, identifying PPDs at a rate more than three times higher than the overall set (positive and negative predictive values were 0.074 and 0.985, respectively). The model's strongest predictors included both well-recognized (e.g., past depression) and less-recognized (differing patterns of blood tests) PPD risk factors. Conclusions Machine learning-based models incorporating EHR-derived predictors, could augment symptom-based screening practice by identifying the high-risk population at greatest need for preventive intervention, before development of PPD.

Clozapine is the only antipsychotic compound indicated for refractory-schizophrenia. However, it is associated with emergent metabolic dysregulation and cardiovascular risk which may lead to mortality. In this study we aimed to explore predictors for mortality in a large cohort of schizophrenia patients treated with long-term clozapine, using the electronic medical records of the largest health care provider in Israel. Among 27,929 patients diagnosed with schizophrenia, 1817 were prescribed clozapine during the years 2012-2014. We compared patients who survived (n=1705) and patients who died (n=112) during the 3-year follow-up period. Socio-demographic background, cardiovascular morbidity, medication prescriptions and health-care utilization were compared between groups. Cox proportional hazard models were used to assess the association of variables with survival. Chronic hypertension was found to be the only metabolic factor associated with significant hazard ratio (HR) for mortality (HR: 1.55 95% CI: 1.03-2.34). Moreover, those who died had more prevalent ischemic heart disease (14% vs 3%, p0.005) as well as more frequent hospitalizations (0.01±0.02 vs 0.11±0.18 average per month, p0.005), for longer periods (2.22±9.87 vs 20.38±33.76 days per month, p0.005). Among those who died, less patients received prescriptions of statins for hyperlipidemia (13.7% vs. 52.9% in survivors, p0.005) and hypoglycemics for diabetes mellitus (16.3% vs. 67.1% in survivors, p0.005). Inadequate treatment of metabolic syndrome, under chronic clozapine treatment, was found to be an independent predictor for mortality. Adequate rigorous regimen for diagnosis and treatment of metabolic risk factors, especially hyperlipidemia and diabetes mellitus, might lower complications rate and prolong life expectancy among this population.

Major depressive disorder (MDD) is associated with alterations in circulatory cytokines, in adults as well as in children and adolescents. Administration of selective serotonin reuptake inhibitors (SSRIs) to MDD pediatric patients modifies cytokine levels. However, most studies only assessed changes over a short time period. In this study, we evaluated long-term effects of the SSRI fluoxetine (FLX) in children and adolescents treated for anxiety and/or MDD, including a high-risk group with pre-treatment suicidality. The study group included ninety-two patients (35 boys and 57 girls) with MDD and/or anxiety disorders, aged 13.90 ± 2.41 years. All patients were treated with FLX and followed for 6 months. The study group included children with pretreatment suicidality (high-risk group;N = 62) and without pretreatment suicidality (N = 30) according to the Columbia Suicide Severity Rating Scale. Plasma concentrations of TNFα, IL-6, and IL-1β were measured by enzyme linked immunosorbent assays before and after six months of treatment. IL-6 and IL-1β significantly increased as a factor of time after 6 months of treatment. The elevation was statistically significant confined to children with pretreatment suicidality. Within the children with pretreatment suicidality, IL-6 levels increased significantly after 6 months only in the children who developed SSRI-associated suicidality. To summarize, an increase in IL-6 levels after 6 months of treatment may be associated with SSRI-emergent suicidality in children with pretreatment suicidality. Further studies are needed to clarify the role and mechanism(s) of IL-6 in the pathogenesis of this life-threatening adverse event.

Objectives: The present study characterized the psychiatric diagnoses and symptoms that led to the administration of antipsychotic medications in children and adolescents with cancer, and to evalua...

Multiple studies have shown that pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD), especially stimulants, are generally effective. There is yet a paucity of empirical data, however, for some common clinical conditions overlooked in the ADHD treatment guidelines. Some examples include: in cases of first line treatment failure, it is unclear whether switching from one type of stimulant to another is beneficial. In cases of comorbid ADHD and severe aggressive/disruptive behavior in children, it is unclear whether the best first-line treatment is stimulants or atypical antipsychotics like risperidone. In cases of ADHD with comorbid anxiety disorders, there is no clear evidence regarding optimal treatment. The objectives of this article are to review these issues and propose possible answers for such clinical dilemmas.

Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol’s side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

Objective: To evaluate the relationship between attention-deficit/hyperactivity disorder (ADHD) severity and propensity for boredom in children with ADHD, both on and off methylphenidate (MPH). Met...

Objectives A meaningful proportion of patients with obsessive-compulsive disorder (OCD) develop symptoms of bipolar depression (BP-D). In the present investigation, we aimed to determine whether quetiapine is efficacious in OCD patients who despite continuous treatment with a selective serotonin reuptake inhibitor developed an acute episode of BP-D. Methods We analyzed 68 charts of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition OCD patients from our outpatient clinic and identified 15 patients who in addition met Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for bipolar II disorder, depressive episode. Eleven (7 men and 4 women, aged 24-54 years) patients for whom quetiapine was added to treat the index episode of BP-D were included. Treatment response was assessed retrospectively and defined as a score of "much improved" or "very much improved" on the Clinical Global Impression-Improvement scale. Results Quetiapine was added for treatment of BP-D in a dose range of 150 to 400 mg (mean, 273 mg). Eight (73%) of the 11 study patients fulfilled the criterion of response, that is a score of "much improve" (4 patients) and "very much improved" (4 patients) on the Clinical Global Impression-Improvement scale. Notably, quetiapine was associated with additional improvement of OCD symptoms in 6 of 8 study responders. Quetiapine was well tolerated. The most frequently detected side effects were drowsiness (5 patients), constipation (4 patients), and orthostatic hypotension (2 patients). Conclusions The revealed beneficial effect of quetiapine addition for acute episode of BP-D in OCD patients maintained on selective serotonin reuptake inhibitor treatment merits further controlled investigation.

Only 30% of patients with major depressive disorder (MDD) reach full recovery or remission. Treatment-resistant depression (TRD) is MDD that does not respond to adequate treatment attempts with at least two antidepressants. TRD is associated more with immune activation than with treatment responsive depression. The current retrospective population-based cross-sectional study, utilizing data from a large nation-wide health maintenance organization in Israel which provides services to estimated 725,000 members, aimed to assess the clinical signs and laboratory markers of autoimmune comorbidity and low-grade inflammation, in patients with TRD. Included were participants aged 18–70 years, diagnosed twice within one year with ICD-9-CM MDD and two control groups, MDD responders (MDD-r) consisting of people with MDD and no TRD and a non-MDD group that included people with no MDD or TRD. The case (570 subjects in TRD group) to control ratio in both control groups (2850 subjects in MDD-r and 2850 subjects in non-MDD control group) was 1:5. Compared to MDD-r, the overall proportion of allergic diseases was higher among the TRD than among the MDD-r [OR 1.52 (1.19–1.94); p ​1:80) antinuclear antibodies [33 (5.79%)] were found among the TRD than among the MDD-r [98 (3.44%); p ​= ​0.011). More allergy and autoimmune comorbidities and presence of low-grade inflammation biomarkers, were found mainly in TRD., Highlights • TRD seems to be associated more with immune activation than with treatment responsive depression (MDD-r). • This study demonstrated higher allergy and autoimmune comorbidities in patients with TRD. • TDR is also characterized by the presence of biomarkers of low-grade inflammation.

Cocaine addiction is an acquired behavioral state developed in vulnerable individuals after cocaine exposure. It is characterized by compulsive drug-seeking and high vulnerability to relapse even after prolonged abstinence, associated with decreased neurogenesis in the hippocampus. This addictive state is hypothesized to be a form of “memory disease” in which the drug exploits the physiological neuroplasticity mechanisms that mediate regular learning and memory processes. Therefore, a major focus of the field has been to identify the cocaine-induced neuroadaptations occurring in the usurped brain’s reward circuit. The neurosteroid dehydroepiandrosterone (DHEA) affects brain cell morphology, differentiation, neurotransmission, and memory. It also reduces drug-seeking behavior in an animal model of cocaine self-administration. Here, we examined the long-lasting effects of DHEA treatment on the attenuation of cocaine-seeking behavior. We also examined its short- and long-term influence on hippocampal cells architecture (neurons and astrocytes). Using a behavioral examination, immunohistochemical staining, and diffusion tensor imaging, we found an immediate effect on tissue density and activation of astrocytes, which has a continuous beneficial effect on neurogenesis and tissue organization. This research emphasizes the requites concert between astrocytes and neurons in the rehabilitation from addiction behavior. Thus, DHEA may serve as a treatment that corrects brain damage following exposure to and abstinence from cocaine.

Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all‐cause mortality in a population‐based cohort of patients with cancer.Materials and Methods: We conducted a 4‐year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality.Results: During 1,051,489 person‐years at risk follow‐up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83–0.95), 0.77 (95% CI: 0.66–0.72), and 0.80 (95% CI: 0.76–0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42–1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04–1.15]; P P Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all‐cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.

Obsessive-compulsive disorder frequently co-occur with schizophrenia causing a significant impairment. There is a paucity of published data on the treatment of such complicated patients. It has been suggested that the combination of antipsychotics and antiobsessive agents is the best treatment for schizophrenia with obsessive-compulsive disorder; however, there is no published data regarding the use of high dose (up to 40 mg/day) escitalopram. This open-label, prospective study was designed to investigate the efficacy, short-term safety and tolerability of escitalopram in doses up to 40 mg in patients with schizophrenia and obsessive-compulsive disorder. Patients were treated with increasing doses of escitalopram for 13 weeks. Thirteen patients (86.67%) completed the study. A significant improvement was observed in the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of Y-BOCS-Obsession and Y-BOCS-Compulsion subscales. Furthermore, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and Clinical Global Impression-severity scale. Escitalopram, up to 40 mg/day was well tolerated and may be beneficial in the management of patients with schizophrenia and obsessive-compulsive disorder. Further studies are needed to confirm this finding and to assess long-term safety.

The aim of this study was to compare impulsivity levels, as assessed by a continuous performance test (CPT), and the correlations between baseline CPT performance and response to methylphenidate (MPH), as assessed by the conjunctive CPT (CCPT), in children with only Diagnostic and Statistical Manual of Mental Disorders, 5th ed. attention-deficit hyperactivity disorder with no oppositional defiant disorder (ADHD/noODD) or with comorbid ODD (ADHD/ODD). Fifty-three children and adolescents were included in the study (ADHD/noODD group, n = 25, 12 women/13 men and ADHD/ODD group, n = 28, eight females/20 males). Attention was assessed at baseline using CCPT. ADHD and ODD severities were assessed at baseline and following a 12-week MPH treatment using the ADHD-rating scale (ADHD-RS) completed by the parent and by a teacher and the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-ODD (K-SADS-ODD) completed by the treating psychiatrist. Higher baseline commission-errors rates (P = 0.0031) in ADHD-RS/parent-child, ADHD-RS/teacher, and K-SADS-ODD scores were detected in ADHD/ODD compared with the ADHD/noODD. Significant improvements in ADHD-RS/parent-child, ADHD-RS/teacher, and K-SADS-ODD scores were achieved following MPH treatment in both groups. Significant correlations were found between baseline CCPT commission-error rates and improvement in ADHD-RS-teacher in ADHD/noODD, but not in ADHD/ODD. Among the ADHD/ODD, but not the ADHD/noODD, a significant correlation was found between baseline CCPT commission-error rates and improvement in K-SADS-ODD. Baseline cognitive impulsivity (as measured by the CCPT) can predict response of ODD to MPH treatment in ADHD/ODD patients.

Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short- and long-term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia, and mood disorders. However, casual relations between cannabis use and these adverse effects are missing. On the other hand, recent research proposed promising therapeutic potential of cannabinoid-based drugs for a wide range of medical conditions, including neurological and psychiatric disorders. The current article presents a contemporary review on the adverse effects, safety, and the therapeutic potential of cannabis and cannabinoid-based drugs. Given the growing popularity in the use of cannabinoid-based drugs for both recreational and medical purposes and their potential harmful effects, there is a need for further investigation in this field.

No diagnostic or predictive instruments to help with early diagnosis and timely therapeutic intervention are available as yet for most neuro-psychiatric disorders. A quantum potential mean and variability score (qpmvs), to identify neuropsychiatric and neurocognitive disorders with high accuracy, based on routine EEG recordings, was developed. Information processing in the brain is assumed to involve integration of neuronal activity in various areas of the brain. Thus, the presumed quantum-like structure allows quantification of connectivity as a function of space and time (locality) as well as of instantaneous quantum-like effects in information space (non-locality). EEG signals reflect the holistic (nonseparable) function of the brain, including the highly ordered hierarchy of the brain, expressed by the quantum potential according to Bohmian mechanics, combined with dendrogram representation of data and p-adic numbers. Participants consisted of 230 participants including 28 with major depression, 42 with schizophrenia, 65 with cognitive impairment, and 95 controls. Routine EEG recordings were used for the calculation of qpmvs based on ultrametric analyses, closely coupled with p-adic numbers and quantum theory. Based on area under the curve, high accuracy was obtained in separating healthy controls from those diagnosed with schizophrenia (p

Recent studies suggest immune function dysregulation in depression and anxiety disorders. Elevated pro-inflammatory cytokines may be a marker for immune system dysregulation. No study assessed the correlation between the levels of cytokines in children and adolescents with depression/anxiety disorders and their parents. In this study, 92 children and adolescents (mean age 13.90 ± 2.41 years) with depression and/or anxiety disorders were treated with fluoxetine. Blood samples were collected before initiation of treatment. One hundred and sixty-four of their parents (mean age 50.6 ± 6.2 years) and 25 parents of healthy children (mean age 38.5 ± 6.2 years) also gave blood samples. Plasma levels of three pro-inflammatory cytokine (TNF-α, IL-6, IL-1β) were measured by enzyme linked immunosorbent assays (ELISA) and compared between depressed/anxious children and their parents. We also compared cytokine levels between parents of children with depression/anxiety and control parents. Mothers of depressed children had higher TNF-α levels than mothers of controls. No significant difference was detected in the fathers. A positive correlation was found between the IL-1β levels of the depressed/anxious boys and their mothers. No such correlation was observed in the fathers. Our conclusions are that higher levels of proinflammatory cytokines may indicate immune system activation in mothers in response to the distress associated with having depressed/anxious offspring. The correlation between IL-1β levels in the mothers and their depressed/anxious children may indicate familial vulnerability to depression and anxiety. Our observation highlights the need for a better understanding of sexual dimorphism in inflammatory responses to stress.

Objectives: This study aimed to evaluate the relationship between baseline test of variables of attention (TOVA) performance, attention-deficit/hyperactivity disorder (ADHD) symptom severity, mood symptoms, proneness to boredom in children with ADHD, and to assess the responses of the various scales to methylphenidate treatment. Methods: Thirty-three children and adolescents with ADHD, aged 7-18 years, were assessed at baseline with TOVA and treated for 3 months thereafter with methylphenidate. The ADHD Rating Scale (ADHD-RS), Short Boredom Proneness Scale (SBPS), Children's Depression Inventory (CDI) scale, and CDI-academic and social subscale (CDI-AS) were administered to all participants at baseline and after 3 months of methylphenidate (MPH) treatment. Results: The baseline TOVA reaction time (RT) and RT variability parameters correlated with baseline SBPS and CDI-AS scores as well as with baseline total CDI scores. Significant improvements were found in ADHD-RS, SBPS, and CDI-AS scores after MPH treatment. The alteration in ADHD-RS correlated with parallel changes in SBPS and CDI-AS scores. Conclusions: Mood and proneness to boredom correlate with poor attention-span in children with ADHD. Improvement in ADHD levels after MPH treatment correlates with a parallel decrease in mood symptoms related to academic achievement and social functioning.

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line antidepressant drug treatment for major depressive disorder (MDD). Treatment-resistant depression (TRD), defined as failure to achieve remission despite adequate treatment, affects ~30% of persons with MDD. The current recommended treatment for TRD is electroconvulsive therapy (ECT), while ketamine is an experimentally suggested treatment. This study aimed to elucidate the transcriptional differences in peripheral blood mononuclear cells (PBMC) between individuals with TRD and a control group without a psychiatric illness; and between patients with TRD, treated with either standard antidepressant drugs alone, or in combination with ECT or ketamine. Additionally, PBMC transcriptomics were compared between treatment responders, following completion of their treatment protocols. Total RNA was extracted from PBMC of the TRD group at two time points, and RNA and miRNA expression were profiled. Multiple mRNAs and miRNAs were found to be modified, with two protein coding genes, FKBP5 and ITGA2B, which are up- and downregulated, respectively; and several miRNAs have shown changes following successful ECT treatment. Further analysis demonstrated the direct functional regulation of ITGA2B by miR-24-3p. Our findings suggest that PBMC expression levels of FKBP5, ITGA2B, and miR-24-3p should be further explored as tentative ECT response biomarkers.

Ras-related C3 botulinum toxin substrate 1 (Rac1), of the Rho small GTPase family, is a key regulator of actin cytoskeleton rearrangement and plays an important role in dendritic morphogenesis. Cocaine produces neuronal alterations, including structural changes in dendritic number and morphology. Emerging data indicate sigma-1 receptors (σ-1Rs) as a promising candidate for the prevention of cocaine craving. Opipramol is a σ-1R agonist approved in some European countries for depression and anxiety. Here we report that opipramol, mediated by Rac1, attenuates cocaine-seeking behavior in a rat model of self-administration. The opipramol effect was shown in two phases. It decreased cocaine-seeking behavior throughout the withdrawal phase and, interestingly, showed a significant reduction of cocaine-primed reinstatement in 75% of the opipramol-treated group (termed 'responders'). All opipramol-treated rats showed a decrease in σ-1R mRNA expression levels in the nucleus accumbens (NAc) versus controls. Responders also exhibited significantly decreased NAc Rac1 mRNA expression levels, compared with non-responder rats. Hence, Rac1 differentiated responders from non-responders. Rac1 correlated positively with σ-1R mRNA levels in opipramol responders. In another experiment, Rac1 inhibitor injected directly into the NAc core decreased active lever presses on the first day of extinction, indicating the critical role of Rac1 in the opipramol effect on drug seeking. We postulate that chronic activation of σ-1R, through a dynamic interaction with Rac1, may suggest a new approach to treat substance use disorder (SUD). Rac1 inhibition is a prerequisite for decreasing drug seeking and rehabilitation, and this can be achieved by opipramol, a medication that can be given during detoxification.

Background Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at risk for having both psychotic and immune disorders, thus, implying a possible link between the two. The aim of the current study was to evaluate the usefulness of the neutrophiles to leukocytes ratio (NLR), an inflammatory marker, as a bio-marker for overt and prodromal psychotic symptoms in 22q11.2DS. Methods Forty-nine individuals with 22q11.2DS (13 with psychotic disorders and 36 without psychotic disorders) and 30 age- and sex-matched healthy controls underwent psychiatric evaluation using a structured psychiatric interview, the Scale of Prodromal Symptoms (SOPS) and the Global Assessment of Functioning (GAF) scale. Blood samples were collected from all participants on the day of assessment. NLR was calculated, compared among the study groups and correlated with SOPS and GAF scores. The non-psychotic 22q11.2DS group was further divided into high- and low-inflammation groups by NLR values and the analyses were done again. Results NLR was higher in the psychotic- and the high-inflammation non-psychotic 22q11.2DS groups compared to the low-inflammation non-psychotic 22q11.2DS group and controls. In the high-inflammation non-psychotic 22q11.2DS group NLR increase was associated with an increase of total negative symptoms scores on SOPS and a decrease in GAF scores. Conclusion Our results suggest the potential utility of NLR as a bio-marker for psychotic disorders and subthreshold prodromal symptoms in 22q11.2DS. Furthermore, they imply that a disequilibrium between the innate and adaptive arms of the immune system facilitates the progression of psychosis in at risk populations. Further longitudinal studies are warranted to validate our findings, as this was a cross sectional observation.

Anxiety disorders are common comorbidities of attention deficit/hyperactivity disorder (ADHD) and conversely, ADHD is prevalent among anxious youths. A variety of treatments, both psychopharmacological and nonpsychopharmacological, are used to manage combined ADHD/anxiety disorder. This article aims to review the literature on the treatment of ADHD with comorbid anxiety disorders, and make evidence-based recommendations for clinical practice. In most cases, when ADHD is the primary condition, stimulants are the first-line of treatment, frequently resulting not only in improvement in ADHD symptoms but also alleviating the symptoms of the comorbid anxiety disorder. Stimulant treatment is relatively safe and well-tolerated in ADHD with comorbid anxiety disorder. When the stimulant administration does not attenuate the severity of the comorbid anxiety disorder, a treatment that targets specifically the anxiety disorder should be added. This recommendation, however, might be challenged by the impressive efficacy of atomoxetine for both the ADHD and anxiety disorder symptoms. Adjunctive cognitive-behavior therapy for anxiety disorder symptoms is strongly recommended and is considered superior to medication alone. Other options include adding pharmacological treatment for the anxiety symptoms. In moderate and severe cases of comorbid Ads, selective serotonin reuptake inhibitors can be added to the stimulants, with the required caution.

Obsessive-compulsive disorder (OCD) is a prevalent and clinically significant comorbid condition in patients with bipolar disorder. Treatment of bipolar disorder/OCD patients is challenging. We report the results of an open-label, short-term, prospective investigation of quetiapine monotherapy in 16 patients (three men and 13 women, aged 18-56 years) hospitalized for acute bipolar depression who in addition met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for OCD. The participants were treated with quetiapine in a dose range of 150-600 mg (mean 347 mg) for a mean duration of 4.3 ± 1.4 weeks (range 3-7 weeks). Eleven (68.8%) of the 16 study participants fulfilled the predefined criteria for response, namely a score of 'very much improved' (four patients) and 'much improved' (seven patients) on the Clinical Global Impression - Improvement scale. Treatment with quetiapine was associated with a statistically significant decrease from baseline in the relevant rating scales for the assessment of depressive, manic and OCD symptoms. Quetiapine was well tolerated. The most frequently reported side effects were sedation, orthostatic hypotension and constipation. Durability of the positive therapeutic effect of quetiapine monotherapy in patients with bipolar disorder/OCD comorbidity and the necessity for subsequent augmentation with anti-OCD agents need to be addressed in future controlled studies.

Background.Community engagement requires driving. However, there is paucity of research focusing on the potential to drive for people with schizophrenia.Purpose.This study aimed to characterize people with schizophrenia by comparing clinical signs, executive functions (EF), and sociodemographic aspects of those holding a driver’s license to those without one.Method.This cross-sectional study used convenience sampling to select 60 ambulatory individuals to participate: 31 with a driver’s license and 29 without one. They completed the Wisconsin Card Sorting Test (WCST) for evaluation of EF and the Positive and Negative Syndrome Scale (PANSS) for symptoms severity evaluation. Data were analyzed using multivariate analyses of covariance and logistic regression models.Findings.Participants with a license had less severe negative symptoms and general psychopathology and better EF and sociodemographic aspects compared to those without a license. Logistic regression revealed significant odds ratios (OR) in general psychopathology (PANSS; OR = 0.963, p = .011) and in the WCST (OR = 0.504, p = .027).Implications.This study offers occupational therapists a data-driven perspective on evaluating potential fitness to drive to enable participation in daily life and well-being of people with schizophrenia.

Aquaporin-4 (AQP4), an astrocyte water channel protein, is the target antigen of serum immunoglobulin G (IgG) autoantibody in neuromyelitis optica spectrum disorders (NMOsd), a group of inflammatory, demyelinating diseases of the central nervous system. Recently, a reduction in blood vessels coverage by AQP4-immunoreactive astrocytes was demonstrated in depressed patients, indicating a role for AQP4 in mood disorders. Moreover, a possible association between depression and serum AQP4-IgG was suggested in a case report of a treatment resistant depression (TRD) patient diagnosed with NMOsd with positive serum AQP4 autoantibodies. We investigated, for the first time, the presence of serum AQP4-IgG in patients with unipolar and bipolar depression and healthy controls (HCs). In this multicenter study, 25 major depressive disorder (MDD) and 25 bipolar disorder (BD) patients, during an acute major depressive episode (MDE), and 30 matched HCs were screened for the presence of serum AQP4-IgG, using a cell-based assay. The MDE patients underwent a repeated AQP4-IgG assessment at a 3-month follow-up visit. The MDE group (N = 50) had illness duration of 12.7 years (SD = 10.5), 12% of them were psychotropic medication-free and 26% were defined as TRD. All MDE patients and HCs, including three BD patients who experienced a manic switch, were seronegative for AQP4-IgG at baseline and follow-up assessments. In conclusion, contrary to our hypothesis, AQP4 autoantibodies were not detected in serum of unipolar and bipolar depressed patients. However, AQP4 may still play a role in the pathogenesis of mood disorders through different mechanisms of action such as altered brain AQP4 expression.

This retrospective, chart review, cohort study compared demographic and clinical characteristics of cannabis -users and non-drug users at first admission due to psychotic symptoms at Geha Mental Health Center, Israel, between August 2002 and December 2013. We assessed the role of current cannabis use as a risk for re-hospitalization during this period as well as the stability of psychotic diagnoses at re-hospitalization. A total of 318 patients were included in the study, of which 106 (33.3%) were cannabis -users. The cannabis-user group had a shorter duration of hospitalization than the non-drug user group but without a significant difference in 5-year re-hospitalization rates. The latter had a higher rate of severe mental illness (SMI) diagnoses at first hospitalization (53.3% vs. 20.3%, respectively), but the difference disappeared at the second hospitalization. The two groups demonstrated a 79-80% rate of conversion from a non-SMI to an SMI diagnosis between the admissions. The results indicate the instability of non-SMI diagnoses at first hospitalization due to psychotic symptoms, regardless of concurrent cannabis use. The high conversion rate from non-SMI to SMI in current cannabis-users may be due to under-diagnosis of SMI at first admission or an effect of cannabis on the development of SMI.

Accumulating data suggest an association between inflammation and schizophrenia and related psychosis. While several studies have established this immune-psychosis association in adult schizophrenia patients, there is very limited data associating inflammation with acute psychosis in children and adolescents. The ratio between neutrophils and lymphocyte, computed from routine blood counts, has been shown to correlate with traditional markers of inflammation, and is therefore considered a proxy-marker for inflammation. Here we report elevated neutrophil to lymphocyte ratio and total leukocyte count in psychotic adolescent inpatients (n = 81, mean age 14.7 years, 52% males) compared to non-psychotic adolescent inpatient (n = 285, mean age 15.9 years, 58% males), in a population of adolescent inpatients with no affective symptomatology. The elevated neutrophil to lymphocyte ratio remained significant after controlling for confounders such as age, BMI, smoking and antipsychotic medication. In a subset of psychotic adolescent inpatients (n = 20, mean duration between blood test 157 days), we found significant decrease in neutrophil to lymphocyte ratio at clinical remission compared with the acute psychotic state. The results suggest that psychosis is associated with peripheral markers of inflammation early in the course of psychiatric pathology, and that inflammation may represent a state that accompanies psychosis and decreases during clinical remission.

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety-eight patients with BD-I who were hospitalized with a depressive episode between 2005 and 2013 were retrospectively followed for 6-months and 1-year rehospitalization rates, as well as time to rehospitalization, according to treatment at discharge: MSs and/or AAPs with or without AD. Multivariable survival models adjusted for covariates known to influence rehospitalization were conducted. Six-months and 1-year rehospitalization rates were significantly lower in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%, P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89, respectively). Time to rehospitalization within 6-months and 1-year was significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P = .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at discharge reduced significantly the adjusted risk of rehospitalization within 6-months (HR = 0.081, 95% CI: 0.016-0.412, P = 0.002) and 1-year (HR = 0.149, 95% CI: 0.041-0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to MS/AAP at discharge from BD-I depressive episode hospitalization is associated with a lower rate of and a longer time to rehospitalization during a 1-year follow up period.

An association between bipolar disorder (BD) and cancer risk has been reported. The purpose of this study was to investigate this association through linkage analysis of a national HMO database and a national cancer registry. All members of the Leumit Health Services (LHS) HMO of Israel from 2000 to 2012 were included. Members with a recorded diagnosis of BD and a record of at least one written or dispensed prescription for pharmacotherapy for treatment of BD were classified as patients with BD. We linked the LHS population with the Israel National Cancer Registry database to capture all cases of cancer reported. Standardized incidence ratios (SIRs) for cancer in the BD population as compared with non-BD LHS members were calculated. A total of 870 323 LHS members were included in the analysis; 3304 of whom met the criteria for inclusion in the BD arm. We identified 24 515 and 110 cancer cases among members without BD and with BD, respectively. Persons with BD were no more likely than other HMO members to be diagnosed with cancer during the follow-up period [SIR, males=0.91, 95% confidence interval (CI): 0.66-1.22; SIR, females=1.15, 95% CI: 0.89-1.47]. Sensitivity analysis using different criteria for positive BD classification (lithium treatment alone or registered physician diagnosis) had no effect on the estimate of cancer risk. A nonstatistically significant association between breast cancer and BD among women was observed (SIR=1.24, 95% CI: 0.79-1.86). These findings do not corroborate previously reported associations between BD and elevated cancer risk.

BackgroundThe 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories.MethodsForty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12–35 years, were assessed at two time points (15.2 ± 2.1 months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB).Results22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS.ConclusionsOur results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

OBJECTIVE 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder whose phenotype includes high rates of a schizophrenia-like psychotic disorder and immune system abnormalities. Thus, 22q11.2DS is an ideal model for studying the relationship between psychosis and inflammation. The aim of the present study was to identify inflammatory markers that may play a role in the pathophysiologic pathways associated with psychosis and cognitive deficits in 22q11.2DS. METHODS Forty-nine individuals with 22q11.2DS (13 with psychotic disorders according to DSM-IV criteria and 36 without psychotic disorders) and 30 age- and sex-matched healthy controls underwent psychiatric and cognitive assessments at an outpatient clinic. Blood samples from all participants were analyzed for C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFα), and IL-1 receptor antagonist levels. The study was conducted between August 2014 and September 2015. RESULTS The 22q11.2DS participants had elevated levels of CRP (P = .004), IL-6 (P = .001), TNFα (P < .001), and IL-10 (P = .028) compared with controls. Furthermore, the psychotic 22q11.2DS participants had higher levels of IL-6 (P < .001) and IL-6/IL-10 ratio (used as an indicator for proinflammatory activation, P < .001) compared with the nonpsychotic 22q11.2DS individuals and controls. IL-6 levels and the IL-6/IL-10 ratio correlated with the severity of the cognitive deficits in the 22q11.2DS participants. CONCLUSIONS Our preliminary findings indicate an involvement of inflammatory processes in the pathophysiology of psychosis and cognitive deficits in 22q11.2DS and are in line with the accumulating evidence for the role of neuroinflammation in nonsyndromic schizophrenia.

Background While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. Methods This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18 weeks and had low levels of vitamin D ( 70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000 IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. Results Twenty four patients were randomly assigned to vitamin D (aged 39.4 ± 9.6 years, 75% males) and the other 23 patients to the placebo arm (aged 42.5 ± 11.2 years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs − 0.4 nmol/l, p, Highlights • This is the first study to explore the effects of vitamin D supplementation in chronic schizophrenia patients on clozapine • In this randomized double-blind study, patients received supplement vitamin D (14,000 IU weekly) or placebo for eight weeks • There was no difference between vitamin D and placebo with regards to severity of psychopathology or metabolic status • There was a trend towards improved cognition following the effect of vitamin D specifically in attention and delayed recall About third of schizophrenia patients do not respond to common antipsychotics and require a clozapine trial. Insufficient levels of serum Vitamin D, the sunshine hormone, were found to be very prevalent among schizophrenia patients. The vitamin has a potent active metabolite with specific receptors in the brain. We investigated the psychiatric, metabolic and cognitive effects of vitamin D supplementation in comparison to placebo in clozapine-treated chronic schizophrenia patients with residual psychotic symptoms. Vitamin D addition was not superior to placebo in reducing psychiatric symptoms or improving the metabolic parameters. However, vitamin D administration was associated with a trend towards improvement in cognitive performance.

22q11.2 deletion syndrome (22q11.2DS) is a relatively common genetic disorder. Due to improvement in pediatric care, affected individuals live into adulthood, some of whom marry or have committed relationships, and reproduce. The current study aimed to identify the factors that discriminate between married and unmarried adults with 22q11.2DS. In the presents study, 90 adults with 22q11.2DS (48 men/42 women), aged 29.8 ± 10.3 years, were included in the analysis. Psychiatric comorbidities, IQ score, and adaptive functioning were assessed using gold-standard diagnostic tools. Demographic factors, marital status, and reproductive status were evaluated by self-reports. Of the sample 25 adults (27.7%) were married and 14 (56%) of those had children. Married, as compared to unmarried individuals, were older, had less psychotic comorbidities, showed higher adaptive functioning in all domains of the Vineland Adaptive Behavior Scale, and had higher rates of independent living and sustained employment. Unexpectedly, married individuals showed higher rates of mood disorders and full scale IQ scores did not discriminate between the groups. We propose that multiple factors are associated with marital status among individuals with 22q11.2DS. Identification of key personal, functional, and social characteristics of those who married and reproduced may help counseling health professionals and clinicians in advising affected individuals and their families.

Introduction: The purpose of this study was to evaluate the relationship between adherence to antidepressants (AD) and all-cause mortality in a population-based cohort of patients with Parkinson's Disease (PD). Methods: From a database of more than 4 million people, 8553 patients with PD who purchased an AD at least once between the years 2008–2011 were retrospectively followed for all-cause mortality over 4-years. Adherence was measured as a ratio between dispensed and prescribed durations and was modeled as: non-adherence (80%, n = 4219) adherence. Multivariable survival analyses adjusted for demographic and clinical variables including physical comorbidities known to influence mortality were conducted, however there was no adjustment for other psychiatric disorders and medications. Results: Unadjusted mortality rates were 20.4%, 25.1%, 23.4% and 25.6% in those classified as non-adherent, poor, moderate and good adherence respectively (χ2 = 18.45, p Conclusions: Our findings suggest that poor adherence to AD is associated with increased all-cause mortality in people with PD. Given the high prevalence of depression and AD effectiveness, efforts to promote adherence should be prioritized in clinical practice.

Keshet, a course for family members of persons' coping with mental illness, was developed to enhance positive family cognitive communication skills. Improving communication with the use of mediation techniques, primarily used by therapists, creates a learning environment viewed as a strategy of Knowledge Translation. To examine the effectiveness of Keshet in improving attitudes, problem solving, communication skills and attenuation of burden a quasi-experimental research design was applied with study and control condition. The same group of participants (N = 38) completed questionnaires at different stages: 3 months prior to course, initiation and completion. Following participation, significant changes were observed in attitudes regarding knowledge of how to cope and interact with family member. A correlation was found between improved knowledge and decline in burden. Implementing interventions which provide caregivers with professional "know-how" leads to lessened burden, thus contributing to maintaining well-being of family caregiver population.

Background Animal models of dementia associated with metabolic abnormalities play an important role in understanding the bidirectional relationships between these pathologies. Rodent strains develop cognitive dysfunctions without alteration of peripheral metabolism following intracerebroventricular administration of streptozotocin (icv-STZ). Objective We aimed to estimate the effect of icv-STZ on cognitive functions and peripheral metabolism in Lewis rats, which are rarely used for the induction of cognitive abnormalities. Methods Inbred adult Lewis rats were treated with single icv-STZ (3 mg/kg). Cognitive functions were assessed using Morris water maze (MWM) test and locomotion by the Open Field test. Metabolic alterations were studied using histological and biochemical analysis of brain and peripheral tissues. Results The icv-STZ induced rapid weight decline during the first two weeks. Thereafter, the rats showed an accelerated weight gain. Three months after the icv-STZ treatment, the rats were severely obese and revealed fatty liver, pancreatic islet hypertrophy, significantly elevated levels of blood insulin, leptin, and adiponectin, but intact peripheral glucose homeostasis. The icv-STZ rats expressed amyloid-β deposits in blood vessels of leptomeningeal area, microgliosis, astrogliosis, and spongiosis in fimbria-fornix area of hippocampus. Locomotor activities of icv-STZ treated and sham-operated rats were similar. In the MWM test, the icv-STZ treated rats demonstrated severely impaired spatial learning during both acquisition and reversal phases. Conclusions Icv-STZ treated Lewis rats develop severe dementia associated with obesity and peripheral metabolic abnormalities. This animal model may be useful for exploring the pathophysiological relationship between obesity and dementia and provides a new tool for development of effective therapy.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present. ispartof: Molecular Psychiatry vol:26 issue:8 pages:1-15 ispartof: location:England status: published