Reduced mismatch negativity predates the onset of psychosis

Background

Individuals with an “At Risk Mental State” have a 20-30% chance of developing a psychotic disorder within two years; however it is difficult to predict which individuals will become ill on the basis of their clinical symptoms alone. We examined whether mismatch negativity (MMN) could help to identify those who are particularly likely to make a transition to psychosis.

Method

41 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 50 controls performed a duration-deviant passive auditory oddball task whilst their electroencephalogram was recorded. The amplitude of the MMN wave was compared between groups using linear regression. The ARMS subjects were then followed for 2 years to determine their clinical outcome.

Results

The MMN amplitude was significantly reduced in the ARMS group compared to controls. Of the at-risk subjects who completed followed up (n = 41), ten (24% of baseline sample) subsequently developed psychosis. The MMN amplitude in this subgroup was significantly smaller across all three recording sites (FZ, F3 and F4) than in the ARMS individuals who did not become psychotic. Conclusion: Among those with the ARMS, MMN amplitude reduction is associated with an increased likelihood of developing frank psychosis.     

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.     

Delusional ideation,manic symptomatology and working memory in a cohort at clinical high-risk for psychosis: A longitudinal study

We followed up a cohort (n = 35) of clients with an “At Risk Mental State” (ARMS) for almost 2 years (mean 21.3 months). At baseline, these clients had taken part in research looking at the relationship between reasoning biases, memory, personality styles and delusional ideation. During the follow-up period, clients underwent a package of intervention from a specialist early detection team. Eighty percent (n = 28) of these clients were successfully re-interviewed. There was improvement across the cohort as a whole, however five participants (17.9%) had made the transition to psychosis at follow-up. Those who had become psychotic had lower levels of manic symptomatology at baseline than those who did not enter the first episode. Further, across the cohort, impaired working memory and delusional ideation at baseline combined to predict 45% of the delusional ideation at follow-up. These preliminary findings suggest that working memory impairments may be linked to the persistence of delusional ideation and that manic symptoms in someone with an ARMS may suggest that such an individual is less likely to develop a frank psychotic episode.     

Hippocampus abnormalities in at risk mental states for psychosis? A cross-sectional high resolution region of interest magnetic resonance imaging study

Background

Hippocampal volume (HV) reduction is well documented in schizophrenia. However, it is still unclear whether this change is a pre-existing vulnerability factor, a sign of disease progression, a consequence of environmental factors, such as drug use, antipsychotic medication, or malnutrition. The timing of HV changes is not well established, but a lack of macrostructural hippocampal brain abnormalities before disease onset would rather support a neuroprogressive illness model.

Aim

To investigate the timing of HV changes in emerging psychosis.

Methods

A cross-sectional MRI study of manually traced HVs in 37 individuals with an At Risk Mental State (ARMS) for psychosis, 23 individuals with First-Episode Psychosis (FEP), and 22 Healthy Controls (HC) was performed. We compared left and right HVs corrected for whole brain volume across groups using analysis of covariance (ANCOVA) with gender as a covariate. Sixteen of 37 ARMS individuals developed a psychotic disorder during follow up (ARMS-T). The mean duration of follow up in ARMS was 25.1 months.

Results

The overall ANCOVA model comparing left HVs across FEP, ARMS and HC indicated a significant general group effect (p < .05) with largest volumes in ARMS and smallest in FEP. ARMS-T subjects had significantly larger left HVs compared to FE but no HV differences compared to HC (p < 0.05). Over all groups, we found an asymmetry between the left and right mean HVs and a strong effect of sex.

Discussion

The present study suggests that macrostructural hippocampal abnormalities probably occur in the context of the first psychotic breakdown.     

Temporal relationship of first-episode non-affective psychosis with cannabis use: A clinical verification of an epidemiological hypothesis

Background

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.

Method

We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57 years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use.

Results

We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank χ² = 23.43, df = 1, p < 0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5 years (27, 45) (for log-transformed AOPT, t = 5.6, df = 110, p < 0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05).

Conclusions

Our results are in favor of a catalytic role for cannabis use in the onset of psychosis.     

Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, −141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and −521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27–0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22–0.54). The genotype of −141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48–5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.     

Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol,prolactin and albumin

Stress and inflammation are thought to play a role in the risk of developing a psychotic disorder. We aimed to identify stress-related biomarkers for psychosis transition in help-seeking individuals with an at-risk mental state (ARMS). We studied 39 ARMS subjects who were attending an Early Intervention Service. We included a control group of 44 healthy subjects (HS) matched by sex and age. Stressful life events and perceived stress were assessed. Stress-related biomarkers were determined in serum (cortisol, prolactin, C-reactive protein and albumin), plasma (fibrinogen) or saliva (morning cortisol, cortisol awakening response). All ARMS were followed-up at our Unit for at least one year. We divided the ARMS group into two subgroups based on the development of a psychotic disorder (ARMS-P, N = 10) or not (ARMS-NP, N = 29). ARMS-P reported more stressful life events and perceived stress than HS and ARMS-NP groups. In relation to baseline stress biomarkers, ARMS-P subjects had increased prolactin and lower albumin levels in serum, when compared to ARMS-NP and HS groups. These results did not change when repeated in a subsample of antipsychotic-naïve ARMS subjects. We also found significant differences between groups in the cortisol secretion after awakening. In a multinomial logistic regression adjusting for age, sex and life stress, prolactin was a predictor of psychosis transition whereas albumin levels had a protective effect. Our study underscores the role of stress and stress-related biomarkers (cortisol awakening response, prolactin and albumin) in the pathogenesis of psychosis.     

Inflammation in psychotic disorders: a population-based study

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n = 45), other nonaffective psychosis (ONAP) (n = 57), affective psychosis (n = 37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.     

Evidence of association of KIBRA genotype with episodic memory in families of psychotic patients and controls

The first genome-wide association study of human memory identified an association between a common T/C polymorphism of the KIBRA gene (rs17070145) and episodic memory performance in normal individuals; subsequent studies have implicated the same polymorphism in Alzheimer’s disease. Since impaired neurocognitive performance, including memory, may be both a core feature of schizophrenia and a candidate endophenotype, we attempted to replicate this association in a total sample of 544 subjects (including patients with psychosis, their unaffected relatives as well as normal individuals). In the combined sample there was a significant association between the KIBRA T allele and better performance in the single principle component of the memory measures, which included immediate and delayed logical and visual memory from the Wechsler Memory Scale (p = 0.019). In the unaffected individuals (patients’ relatives and healthy controls) we observed an association of KIBRA with immediate and delayed logical memory (p = 0.020 and 0.025, respectively), while in patients with psychosis with delayed visual memory (p = 0.05). This study replicates the association between the KIBRA gene and episodic memory and suggests a possibly differential effect of the polymorphism in psychotic and non-psychotic individuals.     

The Early Recognition Inventory ERIraos detects at risk mental states of psychosis with high sensitivity

The identification of patients carrying an increased risk of psychosis is one of the most important demands in schizophrenia research. Currently used diagnostic instruments mainly focus on either attenuated psychotic symptoms and brief limited intermittent psychotic symptoms or solely cognitive basic symptoms. The “Early Recognition Inventory based on IRAOS” (ERIraos) has been developed as a comprehensive assessment of both symptom groups within one scale. We compared the results obtained by ERIraos with an international standard instrument, the “Comprehensive Assessment of At Risk Mental States” (CAARMS) and applied both scales in a sample of 121 outpatients positively tested on a screening checklist for at risk mental states (ARMS). Subsamples were classified as first episode of psychosis, late ARMS with prevalent attenuated psychotic symptoms and/or brief limited intermittent psychotic symptoms, earlier stages of ARMS presenting cognitive basic symptoms as well as a vulnerability group, also differing regarding mean age and psychosocial functioning. Our results point to a higher sensitivity of ERIraos compared to scales that mainly focus on attenuated psychotic symptoms and brief limited intermittent psychotic symptoms. A detailed assessment of cognitive basic symptoms seems to be important in early detection, might be an important focus for therapeutic interventions in ARMS patients and might sustain attempts to alleviate cognitive dysfunction in schizophrenia.     

Amygdalar excitatory/inhibitory circuits interacting with orexinergic neurons influence differentially feeding behaviors in hamsters

Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent.SCZ (N = 25) and BP (N = 24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls.For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites.At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration.     

Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia

The aim of this study was to analyze gene expression in blood of patients with newly-diagnosed schizophrenia during their first psychotic episode and subsequent remission. Whole blood samples were obtained from 32 untreated patients presenting with their first psychotic episode suggestive of schizophrenia and 32 age- and gender-matched controls. Using Affymetrix micoarrays, we identified significantly altered expression of 180 gene probes in psychotic patients compared to controls. A subset of four significantly changed genes was further confirmed with QRT-PCR. The following genes were significantly altered in patients: glucose transporter, SLC2A3 (p < 0.001) and actin assembly factor DAAM2 (p < 0.001) were increased, whereas translation, zinc metallopeptidase, neurolysin 1 and myosin C were significantly decreased (p < 0.05). Expression of these candidate markers was also analyzed in a longitudinal study (12-24 months) in 12 patients who achieved full remission. Interestingly, expression of DAAM2 returned to control levels in patients who were in remission after their first psychotic episode, suggesting that its expression correlates with diseases progression and/or response to treatment. In summary, we identified changes of gene expression from peripheral blood which might help discriminate patients with schizophrenia from controls. While these results are promising, especially for DAAM2 whose polymorphic variants have been found significantly associated with schizophrenia, it will be important to analyze larger cohorts of patients in order to firmly establish changes in gene expression as blood markers of schizophrenia.     

Transition to first episode psychosis in ultra high risk populations: Does baseline functioning hold the key?

BackgroundBaseline functioning has been found to be a strong predictor of transition to psychosis in ultra high risk populations. However, the time course of functioning may enhance prediction. We investigated whether there were different patterns of functioning over time and whether particular temporal patterns were related to baseline characteristics and psychosis outcome.MethodFunctional data was assessed at baseline and after 3 to 6 year follow-up in an ultra high risk sample (n = 158; 92 female, mean age = 19.28 (SD = 3.33), range = 14–29). Using the median score of the GAF and the QLS scale, a ‘High’ and ‘Low’ group (comprising of subjects functioning above or below median at both baseline and follow-up) and a ‘Deterioration’ group and ‘Improving’ group were created.ResultsChi-square analyses showed that the Low and Deteriorating functioning groups were the most likely to develop first-episode psychosis (FEP). Importantly, UHR individuals with deteriorating functioning were at higher risk of transition than those whose functioning was low at baseline but improved over time (GAF: X² = 5.10, df = 1, p = .02; QLS: X² = 9.13, df = 1, p = .003). Binary logistic regression analyses showed that a decline in functioning was more strongly associated with FEP (GAF: p = < .0001; QLS: p < .0001) than the level of baseline functioning (GAF: p = .005; QLS: p = .09). The deteriorating group could not be distinguished from the High group in terms of baseline symptomatology.DiscussionWith the addition of the ‘low functioning’ criterion to the UHR criteria, we may miss out on some true positive cases. Limiting our attention to baseline poor functioning may therefore distort the picture in terms of risk for psychosis.     

Outcomes for 236 patients from a 2‐year early intervention in psychosis service

Objective: To examine: i) changes in key outcome measures over time in treatment in a representative first‐episode psychosis treatment cohort and ii) baseline predictors of service disengagement. Method: Baseline characteristics of 236 patients were examined for associations with outcomes over time using generalized estimating equation models. The data on disengagement were analysed using logistic regression. Results: After controlling for admission scores, patients showed consistently improved outcomes while in treatment on functional recovery (unemployment, P < 0.01; HoNOS, P < 0.001; the Quality of Life Scale, P < 0.001; GAF, P < 0.05) but not symptomatology (as assessed by the PANSS and substance abuse). The 64 (33%) who disengaged were more likely to be unemployed (P < 0.01) and have higher HoNOS (P < 0.01) and GAF (P < 0.05) scores at baseline. Conclusion: This evaluation has shown significant improvements in psychosocial functioning but not psychopathology during treatment at an Early Intervention for Psychosis Service. Despite attempts to retain patients, there is a high rate of treatment discontinuation.     

Comorbid Depressive and Anxiety Disorders in 509 Individuals With an At-Risk Mental State: Impact on Psychopathology and Transition to Psychosis

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients.Key words: psychosis, schizophrenia, ultra high risk, ARMS, prodromal, attenuated psychosis, psychosis risk, depression, anxiety     

A longitudinal study of neurocognitive function in individuals at-risk for psychosis

IntroductionClinically defined prodromal diagnostic criteria identify at-risk individuals with a 35–40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.MethodsA comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed.ResultsAt-risk subjects performed more poorly than healthy subjects (t = 2.93, P = 0.01), but better than first episode subjects (t = 4.72, p < 0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N = 11; z = − 1.2), while those at-risk subjects who did not progress to psychosis (N = 17) performed better (z = − 0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis.ConclusionNeurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.     

The WERCAP Screen and the WERC Stress Screen: psychometrics of self-rated instruments for assessing bipolar and psychotic disorder risk and perceived stress burden

Background

Identification of individuals in the prodromal phase of bipolar disorder and schizophrenia facilitates early intervention and promises an improved prognosis. There are no current assessment tools for clinical risk symptoms of bipolar disorder, and psychosis-risk assessment generally involves semi-structured interviews, which are time consuming and rater dependent. We present psychometric data on two novel quantitative questionnaires: the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen for assessing bipolar and psychotic disorder risk traits, and the accompanying WERC Stress Screen for assessing individual and total psychosocial stressor severities.

Methods

Prevalence rates of the WERCAP Screen were evaluated among 171 community youth (aged 13–24 years); internal consistency was assessed and k-means cluster analysis was used to identify symptom groups. In 33 participants, test–retest reliability coefficients were assessed, and ROC curve analysis was used to determine the validity of the psychosis section of the WERCAP Screen (pWERCAP) against the Structured Interview of Psychosis-Risk Symptoms (SIPS). Correlations of the pWERCAP, the affectivity section of the WERCAP Screen (aWERCAP) and the WERC Stress Screen were examined to determine the relatedness of scores with cognition and clinical measures.

Results

Cluster analysis identified three groups of participants: a normative (47%), a psychosis–affectivity (18%) and an affectivity only (35%) group. Internal consistency of the aWERCAP and pWERCAP resulted in alphas of 0.87 and 0.92, and test–retest reliabilities resulted in intraclass correlation coefficients of 0.76 and 0.86 respectively. ROC curve analysis showed the optimal cut-point on the pWERCAP as a score of >30 (sensitivity: 0.89; specificity: 1.0). There was a significant negative correlation between aWERCAP scores and total cognition (R = −0.42), and between pWERCAP scores and sensorimotor processing speed. Total stress scores correlated significantly with scores on the aWERCAP (R = 0.88), pWERCAP (R = 0.62) and total cognition (R = −0.44).

Conclusions

Our results show that the WERCAP Screen and the WERC Stress Screen are easy to administer and derived scores are related to cognitive and clinical traits. This suggests that their use could have particular benefits for epidemiologic studies and in busy clinical settings. Longitudinal studies would be required to evaluate clinical outcomes with high questionnaire scores.     

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.     

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.