Phenomenological and Cognitive Features Associated With Auditory Hallucinations in Clinical and Nonclinical Voice Hearers.

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVH) are central features of schizophrenia (SZ). However, AVH also occur in a small percentage of the general population who do not have a need for care, termed nonclinical voice hearers (NCVH). We sought to determine the degree to which the experience of AVH was similar in NCVH and in people with schizophrenia (PSZ) and evaluate the degree to which NCVH shared other features of SZ such as delusional beliefs, cognitive impairment, and negative symptoms. STUDY DESIGN: We recruited 76 people with a DSM-V diagnosis of SZ/schizoaffective disorder (PSZ; 49 with current AVH, 27 without), 48 NCVH, and 51 healthy controls. Participants received a broad battery of clinician-administered and self-report symptom assessments and a focused cognitive assessment. STUDY RESULTS: The AVH of NCVH and PSZ shared very similar sensory features. NCVH experienced less distress, had greater control over their AVH, and, unlike PSZ, rarely heard 2 voices speaking to each other. NCVH demonstrated a wide range of deeply held unusual beliefs, but reported less paranoia, and fewer first-rank symptoms such as passivity and alterations in self-experience. NCVH showed no evidence of cognitive deficits or negative symptoms. CONCLUSIONS: The AVH in NCVH and PSZ demonstrate important similarities as well as clear differences. Specific features, rather than the presence, of AVH appear to determine the need for care. NCVH do not share the cognitive and motivational deficits seen in PSZ. These results suggest that AVH and unusual beliefs can be separated from the broader phenotype of SZ.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) ­ a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = ­0.75) and in negative symptoms (Cohen d = ­0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.

OBJECTIVE: Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. METHODS: Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). RESULTS: Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. CONCLUSIONS: Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

Cognitive effort avoidance and detection in people with schizophrenia.

Many people with schizophrenia exhibit avolition, a difficulty initiating and maintaining goal-directed behavior, considered to be a key negative symptom of the disorder. Recent evidence indicates that patients with higher levels of negative symptoms differ from healthy controls in showing an exaggerated cost of the physical effort needed to obtain a potential reward. We examined whether patients show an exaggerated avoidance of cognitive effort, using the demand selection task developed by Kool, McGuire, Rosen, and Botvinick (Journal of Experimental Psychology. General, 139, 665-682, 2010). A total of 83 people with schizophrenia or schizoaffective disorder and 71 healthy volunteers participated in three experiments where instructions varied. In the standard task (Experiment 1), neither controls nor patients showed expected cognitive demand avoidance. With enhanced instructions (Experiment 2), controls demonstrated greater demand avoidance than patients. In Experiment 3, patients showed nonsignificant reductions in demand avoidance, relative to controls. In a control experiment, patients showed significantly reduced ability to detect the effort demands associated with different response alternatives. In both groups, the ability to detect effort demands was associated with increased effort avoidance. In both groups, increased cognitive effort avoidance was associated with higher IQ and general neuropsychological ability. No significant correlations between demand avoidance and negative symptom severity were observed. Thus, it appears that individual differences in general intellectual ability and effort detection are related to cognitive effort avoidance and likely account for the subtle reduction in effort avoidance observed in schizophrenia.

The MATRICS Consensus Cognitive Battery (MCCB): clinical and cognitive correlates.

The purpose of this study was to examine the cognitive and clinical correlates of the MATRICS Consensus Cognitive Battery (MCCB) which was originally developed to be an endpoint for cognitive enhancement clinical trials. In a sample of 117 people with schizophrenia and 77 healthy control participants we found the following: a) the MCCB was highly sensitive to the type and level of impairment typically observed in schizophrenia, b) the MCCB composite score was highly correlated with WASI Estimated Full Scale IQ score, c) that the MCCB domain scores were generally moderately-highly intercorrelated, d) that MCCB performance was minimally related to clinical symptom type and severity, and e) the MCCB is sensitive to employment status with better performance in employed vs. unemployed patients. These data support the validity of the MCCB as a sensitive measure of cognitive impairment in schizophrenia and suggest that MCCB performance is relevant for functional outcome. The data also suggest that the MCCB domain scores may offer limited resolution on discrete cognitive functions.

Anticipatory vs. consummatory pleasure: what is the nature of hedonic deficits in schizophrenia?

Recent research has distinguished between anticipatory and consummatory pleasure. In the current study, we examined the psychometric properties of the Temporal Experience of Pleasure Scale (TEPS) to determine whether reliability and validity findings reported in previous research replicate in an additional sample of schizophrenia patients. Participants included 86 individuals with schizophrenia and 59 demographically matched healthy controls. Inconsistent with previous research, patients differed from controls in their reports of consummatory (TEPS-CON), but not anticipatory (TEPS-ANT) pleasure. We also failed to replicate some important correlational findings reported in previous research indicating relationships between the TEPS-ANT subscale and external validators. Analyses of the stability of the TEPS subscales were conducted in a sub-group of patients (n=19), and indicated excellent stability for the TEPS-CON (ICC (intraclass correlation coefficient)=0.93), but somewhat lower stability for the TEPS-ANT subscale (ICC=0.74). These findings suggest that additional studies are needed using the TEPS, as well as other measures, to determine the nature of anhedonia in individuals with schizophrenia.