Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia.

The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC50 above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment.

The effects of antipsychotic medication on factor and cluster structure of neurologic examination abnormalities in schizophrenia.

This study extends a previous study of the factor structure of the neurologic examination in unmedicated schizophrenia, utilizing cluster analysis and adding a medicated condition. We administered a modified version of the Neurologic Evaluation Scale (NES) on two occasions to 80 patients with schizophrenia or schizoaffective disorder, once while on antipsychotic medications and once while off medication. Data were distilled by combining right- and left-side scores, and by excluding rarely abnormal and unreliable items from the analysis. Principal components analysis yielded an intuitive four-factor solution in the unmedicated condition, but an inscrutable five-factor solution during medication. Cluster analysis revealed three groups: normal, cognitively impaired, and diffusely impaired. These results were also less interpretable with data from the medicated condition. Neurologic performance was better in the medicated than in the unmedicated condition. As is the case with other domains of symptoms and performance in schizophrenia, relationships among neurologic exam variables are altered by the presence of antipsychotic medication.

Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia.

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT2 receptor complex.