Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications

OBJECTIVE: Patients with schizophrenia have deficits in attention, cognition, and information processing. Measures such as P50 suppression are used to study cognitive and attentional dysfunction among these patients. P50 suppression is an operational measure of sensory gating that can be assessed by averaging electroencephalographic responses to multiple pairs of auditory clicks separated by 500 msec. Normally, the P50 response to the second click is smaller than the response to the first click. Many studies have demonstrated that schizophrenia patients have deficient P50 suppression, meaning that the difference between the first and second clicks is not as large as normal. Atypical antipsychotic medications may have superior clinical efficacy for negative symptoms and cognitive deficits. It is important, therefore, to evaluate the effects of atypical antipsychotic medications on measures such as P50 suppression. METHOD: P50 suppression of 13 patients with schizophrenia receiving clinically effective doses of clozapine, olanzapine, or risperidone (classified as atypical antipsychotic medications) was compared to that of 13 patients receiving conventional antipsychotic medications. RESULTS: The patient groups did not differ on clinical or demographic measures. The patients receiving atypical antipsychotic medications had normal-range P50 suppression (mean=72%). In contrast, the patients receiving typical antipsychotic medications had dramatically lower P50 suppression (mean=27%). CONCLUSIONS: The results support the hypothesis that patients treated with atypical antipsychotic medications have normal P50 measures of sensory gating. Longitudinal within-subjects studies are warranted to clarify the mechanisms mediating this effect.     

Bullying in clinical high risk for psychosis participants from the NAPLS-3 cohort

Purpose

Bullying is associated with a heightened risk for poor outcomes, including psychosis. This study aimed to replicate previous findings on bullying prevalence in clinical high-risk (CHR) individuals, to assess the longitudinal course of clinical and functional variables between bullied and non-bullied CHR and the association of bullying with premorbid functioning, clinical outcome, transition to psychosis and risk of violence.

Methods

The sample consisted of 691 CHR participants and 96 healthy controls. Participants reported whether they had experienced bullying and how long it had lasted. Assessments included DSM-5 diagnoses, attenuated psychotic symptoms, negative symptoms, social and role functioning, depression, stress, premorbid functioning, and risk of violence. The bullied and non-bullied CHR groups were compared at baseline and further longitudinally on clinical and functioning variables and transition to psychosis.

Results

Bullying was more prevalent among CHR individuals than healthy controls. Bullied CHR had a higher prevalence of PTSD and more severe depression and stress at baseline than non-bullied CHR. There was no impact of bullying on clinical and functional variables over time. Bullying was not related to final clinical status or transition to psychosis. However, bullied participants had poorer premorbid functioning and a greater risk of violence.

Conclusion

While bullying may not impact the likelihood of CHR individuals to transition to psychosis, it may be a risk factor for development of the at-risk state and may be related to a greater risk of violence. Future studies should consider bullying perpetration among CHR individuals.

     

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes.     

P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment.

BACKGROUND: Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. RESULTS: As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.     

Social functioning in young people at risk for schizophrenia

Deficits in social functioning are potential risk factors for schizophrenia. Social functioning was assessed in 55 individuals "at risk" for schizophrenia, 16 first episode patients with schizophrenia and 45 normal comparison subjects. The Social Adjustment Inventory for Children and Adolescents (SAICA) was administered to adolescents <18 and the Social Adjustment Scale (SAS-SR) to young adults >17. The at risk and first episode groups significantly differed from the normal subjects on measures of social functioning in the domains of peer, family, work and school relationships. Individuals at risk for schizophrenia have significant functional deficits which may be potential indicators of increased vulnerability for psychosis.