Type 2 diabetes among persons with schizophrenia and other psychotic disorders in a general population survey

Schizophrenia and other psychotic disorders are associated with increased risk of developing type 2 diabetes. However, previous studies are mainly based on clinical samples where the comorbidity may be stronger. We investigated in a general population survey the prevalence of type 2 diabetes in persons with psychotic disorders and in users of antipsychotic medication. The study was based on a nationally representative two-stage cluster sample of 8,028 persons aged 30 or over from Finland. Diagnostic assessment of psychotic disorders combined SCID-I interview and case note data. Prevalences of type 2 diabetes, adjusting for age and sex, were estimated by calculating predicted marginals. The prevalence estimate of type 2 diabetes was 22.0% among subjects with schizophrenia, 13.4% among subjects with other nonaffective psychosis and 6.1% in subjects without psychotic disorders. Only two subjects (3.4%) with affective psychosis had type 2 diabetes. Users of all types of antipsychotic medication had increased prevalence of type 2 diabetes. Our results suggest that type 2 diabetes is a major health concern among persons with schizophrenia and other nonaffective psychotic disorders and also in users of antipsychotic medication, but persons with affective psychosis in the general population may not have increased prevalence of type 2 diabetes.     

A comparison of neuropsychological dysfunction in first-episode psychosis patients with unipolar depression, bipolar disorder, and schizophrenia

The severity and profile of cognitive dysfunction in first episode schizophrenia and psychotic affective disorders were compared before and after antipsychotic treatment. Parallel recruitment of consecutively admitted study-eligible first-episode psychotic patients (30 schizophrenia, 22 bipolar with psychosis, and 21 psychotic depression) reduced confounds of acute and chronic disease/medication effects as well as differential treatment and course. Patient groups completed a neuropsychological battery and were demographically similar to healthy controls (n = 41) studied in parallel. Prior to treatment, schizophrenia patients displayed significant deficits in all cognitive domains. The two psychotic affective groups were also impaired overall, generally performing intermediate between the schizophrenia and healthy comparison groups. No profile differences in neuropsychological deficits were observed across patient groups. Following 6 weeks of treatment, no patient group improved more than practice effects seen in healthy individuals, and level of performance improvement was similar for affective psychosis and schizophrenia groups. Although less severe in psychotic affective disorders, similar profiles of generalized neuropsychological deficits were observed across patient groups. Recovery of cognitive function after clinical stabilization was similar in mood disorders and schizophrenia. To the extent that these findings are generalizable, neuropsychological deficits in psychotic affective disorders, like schizophrenia, may be trait-like deficits with persistent functional implications.     

Mobility limitations in persons with psychotic disorder: findings from a population-based survey

BACKGROUND: There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. RESULTS: Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. CONCLUSION: Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder.     

Activities of daily living,social functioning and their determinants in persons with psychotic disorder

ObjectiveThe determinants of everyday functioning in persons with psychotic disorder have not been widely studied in community dwelling samples. Our aim was to investigate limitations in everyday functioning among subjects with psychotic disorders in a population-based study.MethodEveryday functioning was assessed in a nationally representative sample of 7112 persons aged 30+ using interviewer observations and self-reports, while verbal fluency and memory were also measured. Diagnostic assessment of DSM-IV psychotic disorders was based on SCID interview and case-note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia (n = 61), other non-affective psychotic disorders (ONAP) (n = 79) and affective psychoses (n = 45).ResultNon-affective psychotic disorder was significantly associated with limitations in everyday functioning, as well as with deficits in verbal fluency and memory. Negative symptoms, depression, age, gender, verbal memory deficits, and reduced visual acuity were predictors of limitations in everyday functioning even after controlling for sociodemographic factors and chronic medical conditions, and difficulties in social functioning were also related to expressive speech problems.ConclusionPersons with schizophrenia and ONAP have significantly more problems in everyday functioning than the general population. One significant predictor of problems was reduced visual acuity, which at least in some situations could be easily corrected.     

Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders

Background

Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.

Methods

Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis > alcohol > cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n = 24) was 466.6 mg ± 227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.

Results

On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p = 0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p < 0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r = − 0.524; p = 0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.

Conclusion

These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.     

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = ?0.39) and hippocampal (d = ?0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = ?0.34) and affective psychosis (d = ?0.42), and early-onset schizophrenia showed lower hippocampal (d = ?0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = ?0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.     

Intracranial and subcortical volumes in adolescents with early‐onset psychosis: A multisite mega‐analysis from the ENIGMA consortium

Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen''s d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early‐onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis.     

Predictors of psychosis: a 50-year follow-up of the Lundby population

Behavioural and neuropsychological vulnerability have been associated with an increased risk of psychosis. We investigated whether certain clusters of premorbid behavioural and personality-related signs and symptoms were predictors of nonaffective and/or affective psychosis and schizophrenia, respectively, in a 50-year follow-up of an unselected general community population. Total population cohorts from the same catchment area in 1947 (n = 2,503) and 1957 (n = 3,215) that had been rated for behavioural items and enduring symptoms were followed up to 1997 regarding first-incidence of DSM-IV nonaffective and/or affective psychosis. Attrition was 1–6%. The influence of the background factors, aggregated in dichotomous variables (predictors), on time to occurrence of nonaffective and/or affective psychosis was assessed by means of Cox regression models. In multivariate models the predictors nervous-tense, blunt-deteriorated, paranoid-schizotypal and tired-distracted were significantly associated with subsequent nonaffective and/or affective psychosis. In simple models, down-semidepressed, sensitive-frail and easily hurt were significantly associated with development of psychosis. When schizophrenia was analysed separately nervous-tense remained significant in the multivariate model, although blunt-deteriorated, paranoid-schizotypal and tired-distracted did not; and abnormal-antisocial reached significance. To conclude, we found some evidence for anxiety-proneness, affective/cognitive blunting, poor concentration, personality cluster-A like traits and interpersonal sensitivity to be associated with general psychosis vulnerability.     

Diagnostic specificity of the insular cortex abnormalities in first-episode psychotic disorders

Volume reductions of the insular cortex have been described in schizophrenia, but it remains unclear whether other psychotic disorders such as affective psychosis also exhibit insular cortex abnormalities. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the anterior (short) and posterior (long) insular cortices in 162 first-episode patients with various psychotic disorders (46 schizophrenia, 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses) and 62 age- and gender-matched healthy comparison subjects. Patients with schizophrenia showed bilateral volume reduction of the anterior and posterior insular cortices compared with controls, but the remaining first-episode psychosis subgroups had normal insular volumes. The volumes of these insular subregions were significantly smaller in schizophrenia patients than in patients with schizophreniform disorder or affective psychoses. There was no association between the insular cortex volume and daily dosage or type of antipsychotic medication in any patient group. These findings suggest that the widespread volume reduction of the insular cortex is specific to established schizophrenia, implicating its role in the neurobiology of clinical characteristics associated with schizophrenia.     

Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia

Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia.The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively.Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6 months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder.The concentration of Trx1 in the patients with first episode of psychosis was 1.5 ± 1.0 ng/ml and 0.8 ± 0.6 ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5 ± 0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p < 0.016 and p < 0.001, respectively).Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.     

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective

To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission.

Methods

Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with (n = 152) or without (n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (?50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ?50% MRS decrease, and a MRS score ? 12, respectively) were analyzed.

Results

Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation (p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received (p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone (p = 0.01).

Limitations

Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.

Conclusions

The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.     

Sociodemographic and clinical correlates of migrant status in adults with psychotic disorders: data from the Australian Survey of High Impact Psychosis

Objective.The links between migrant status and psychosis have attracted considerable attention in recent decades. The aim of the study was to explore the demographic and clinical correlates of migrant v. Australia-born status in individuals with psychotic disorders using a large community-based sample.Method.Data were drawn from a population-based prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas in 2010. Logistic regression was used for the main analyses, examining associations of migrant status with sociodemographic and clinical variables.Results.Of the 1825 participants with psychotic disorders, 17.8% (n = 325) were migrants, of whom 55.7% (n = 181) were male. Compared to Australia-born individuals with psychosis, migrants were more likely to be currently married, to have completed a higher level at school, to have left school later, and to be employed with full-time jobs. Migrants with psychosis were either no different from or less impaired or disadvantaged compared to their Australian-born counterparts on a range of clinical and demographic variables.Conclusions.In a sample of individuals with psychotic disorders, there was no evidence to suggest that migrant status was associated with worse clinical or socio-economic outcomes compared to their native-born counterparts.Key words: Clinical factors, migrants, psychotic disorders, schizophrenia, sociodemographic factors     

Social Deprivation,Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London

Although urban birth, upbringing, and living are associated with increased risk of nonaffective psychotic disorders, few studies have used appropriate multilevel techniques accounting for spatial dependency in risk to investigate social, economic, or physical determinants of psychosis incidence. We adopted Bayesian hierarchical modeling to investigate the sociospatial distribution of psychosis risk in East London for DSM-IV nonaffective and affective psychotic disorders, ascertained over a 2-year period in the East London first-episode psychosis study. We included individual and environmental data on 427 subjects experiencing first-episode psychosis to estimate the incidence of disorder across 56 neighborhoods, having standardized for age, sex, ethnicity, and socioeconomic status. A Bayesian model that included spatially structured neighborhood-level random effects identified substantial unexplained variation in nonaffective psychosis risk after controlling for individual-level factors. This variation was independently associated with greater levels of neighborhood income inequality (SD increase in inequality: Bayesian relative risks [RR]: 1.25; 95% CI: 1.04–1.49), absolute deprivation (RR: 1.28; 95% CI: 1.08–1.51) and population density (RR: 1.18; 95% CI: 1.00–1.41). Neighborhood ethnic composition effects were associated with incidence of nonaffective psychosis for people of black Caribbean and black African origin. No variation in the spatial distribution of the affective psychoses was identified, consistent with the possibility of differing etiological origins of affective and nonaffective psychoses. Our data suggest that both absolute and relative measures of neighborhood social composition are associated with the incidence of nonaffective psychosis. We suggest these associations are consistent with a role for social stressors in psychosis risk, particularly when people live in more unequal communities.Key words: psychosis, epidemiology, urban, social environment, inequality, deprivation, Bayesian modeling, schizophrenia     

Longitudinal changes in brain structure following the first episode of psychosis

Both schizophrenia and bipolar disorder have been associated with progressive changes in grey matter (GM) volume. However, the temporal trajectories of these changes are poorly understood. The aim of this study was to assess longitudinal changes in grey matter volume subsequent to the first episode of schizophrenia and of affective psychoses. Adolescent patients with a first episode psychosis (n = 26) were scanned twice using magnetic resonance imaging, at first presentation and after a 3-year follow-up period. An age-matched group of healthy volunteers (n = 17) was scanned at the same time points. Within-group and between-group changes in regional grey matter volume were examined using voxel-based morphometry. There were significant group by time interactions (p_FDRcorr < 0.05) in the frontal, temporal, parietal, cerebellar cortex, and in the thalamus, mainly reflecting longitudinal reductions in the controls but not in the patients. Subdivision of the patient group revealed that there were similar longitudinal reductions in patients with affective psychoses as in the controls but no volumetric changes in patients with schizophrenia. Psychosis with onset in adolescence or early adulthood may be associated with a delay or a loss of longitudinal reductions in regional grey matter volume that normally occur at this stage of development. These changes may be specific to schizophrenia.     

Coronary heart disease and cardiac conduction abnormalities in persons with psychotic disorders in a general population

We investigated the prevalence of coronary heart disease (CHD) and myocardial infarction (MI) in persons with DSM-IV psychotic disorders. We also examined cardiac conduction abnormalities, and the role of antipsychotic medication in them. The study was based on a nationally representative survey of 8028 persons aged 30 years or over from Finland. Diagnoses of CHD and MI were based on electrocardiographic findings, health examination, and register information. QTc was calculated using the Bazett formula, and Minnesota classification was used for conduction abnormalities. We found that large Q-waves suggesting past MI were significantly more frequent in persons with schizophrenia, while the prevalence of CHD in persons with psychotic disorders did not differ significantly from the remaining study sample. Prevalence of prolonged QTc interval was significantly increased in persons with schizophrenia and in users of typical antipsychotics. However, low-potency antipsychotic use but not diagnosis of schizophrenia remained an independent predictor of prolonged QTc interval in a logistic regression. Low-potency antipsychotic use was associated with ventricular conduction defects, and high-potency antipsychotic use with premature beats. Symptoms and signs of CHD should be actively monitored patients with schizophrenia, and the electrocardiogram should be monitored for all types of changes in persons receiving antipsychotic medication.     

Diagnostic stability in adolescent onset psychotic disorders

The purpose was to examine the long-term stability of a diagnosis of psychotic disorder in adolescence and to focus on diagnostic change over time. A total of 88 patients with a first episode of early onset psychosis (before 19 years) were followed up an average of 10.5 years (range 5.1-18.2) after admission. This report includes the 68 patients who could be traced and interviewed with the Positive and Negative Symptom Scale and lifetime Structured Clinical Interview for DSM-IV diagnosis. An initial diagnostic split between schizophrenia spectrum and affective disorder had a good (> 80 %) Positive Predictive Validity and Sensitivity. The main diagnostic shift was an influx to schizophrenia spectrum disorder (n = 6). These patients resembled the stable affective group (n = 27) in premorbid and prodromal aspects but changed over time to resemble the poor outcome of the stable schizophrenia spectrum group (n = 28) albeit with fewer negative symptoms and a better social function. Family history of nonaffective psychosis in first or second degree relatives was often found in the "change to schizophrenia group". A diagnosis in adolescence of schizophrenia spectrum or affective psychotic disorder is usually stable over time. A subgroup of non-schizophrenia patients go on to develop a schizophrenia spectrum disorder.     

Hospital Admission With Infection During Childhood and Risk for Psychotic Illness—A Population-based Cohort Study

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0–13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03–1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08–1.40). Bacterial infections and central nervous system infections during preadolescence (10–13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21–2.05) and HR 1.96 (95% CI 1.05–3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.Key words: psychosis, prenatal, schizophrenia, epidemiology, cohort study     

Neurophysiological Evidence of Corollary Discharge Function During Vocalization in Psychotic Patients and Their Nonpsychotic First-Degree Relatives

Predictions about sensations resulting from motor acts are instantiated through neural mechanisms such as the corollary discharge. With each action, the corollary discharge provides an unconscious comparison between predicted and actual sensations resulting from the action; closer matches result in greater suppression of sensation. This mechanism is disrupted in schizophrenia (SZ) and may contribute to, or reflect a failure to, distinguish self- from externally generated experiences, a hallmark of psychosis. We asked whether disruption is specific to SZ or is seen in other psychotic illnesses and in first-degree relatives of psychotic patients. Corollary discharge function was assessed in SZ patients (n = 30), schizoaffective (SA) patients (n = 19), bipolar patients with a history of psychosis (BPP; n = 39), nonpsychotic relatives of SZ (n = 30), SA (n = 23), and BPP (n = 50) patients, and healthy controls (n = 43). The N1 component of the event-related potential, reflecting auditory cortical responses to sounds, was elicited by speech sound onset as subjects talked and later when they listened to a recording of those sounds. N1 was suppressed during talking compared to N1 during listening, consistent with the suppressive action of the corollary discharge mechanism. Suppression was significantly reduced in SZ and BPP patients, with a similar trend in the smaller SA group. Patient groups did not differ, and unaffected relatives did not differ from controls or probands. The failure to monitor sensations resulting from self-generated actions, implicating corollary discharge dysfunction, may be a common feature across affective and nonaffective psychosis. Data from unaffected family members do not indicate that this is a marker of psychosis risk.Key words: psychosis, corollary discharge, ERP, N1, first-degree relatives     

Clinical predictors of acute response with quetiapine in psychotic mood disorders

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.     

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

A convergence of evidence shows that use of Cannabis sativa is associated with increased risk of developing psychotic disorders, including schizophrenia, and earlier age at which psychotic symptoms first manifest. Cannabis exposure during adolescence is most strongly associated with the onset of psychosis amongst those who are particularly vulnerable, such as those who have been exposed to child abuse and those with family histories of schizophrenia. Schizophrenia that develops after cannabis use may have a unique clinical phenotype, and several genetic polymorphisms may modulate the relationship between cannabis use and psychosis. The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia. Anandamide signaling in the central nervous system may be particularly important. Δ⁹-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects. CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties. Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-015-0382-6) contains supplementary material, which is available to authorized users.Key Words: Cannabinoids, schizophrenia, psychosis, cannabidiol, cannabis, endocannabinoid