10. Brain Structure Biomarkers at the Psychosis/Nonpsychosis Interphase: Findings From the Bipolar–Schizophrenia Network for Intermediate Phenotypes

Abstract

International Congress on Schizophrenia Research S10 Plenary correlated with AL at trend level (adjusted R = −.251, P = .070). No significant associations were found for negative symptoms (P = .582). AL decreased after treatment with olanzapine, risperidone, or quetiapine was commenced in patients with SCZ and FEP between the baseline assessment and the 6-and 12-week follow-up. Conclusion: Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful model that takes stress, long-term adaptation, and its failures into account to further understand the pathophysiology of schizophrenia. Background: Elevated levels of proinflammatory cytokines have provided evidence in support of the inflammatory hypothesis of schizophrenia. Most studies in schizophrenia have reported cytokine levels in peripheral blood, but the number of studies investigating cytokines in CSF in schizophrenia is still very small and those studies typically have small sample sizes. Of the cytokines studied, IL-6 and IL-8 have been most commonly measured and reported while abnormalities in other cytokines, such as TNF-α, have not been reported in CSF of patients with schizophrenia. Therefore, our aim was to study a panel of cytokines in cerebrospinal fluid of a decently large sample of patients with schizophrenia and healthy volunteers. In addition, we examined correlations between these cytokines and psychiatric symptoms. Methods: Thirty-three patients with schizophrenia-spectrum disorders and 23 healthy volunteers underwent a lumbar puncture. CSF of 15-25 cc was obtained from each subject. CSF cytokine (IL-1β, IL-2, IL-4, IL-6, IL-8, and TNF-α) concentrations were determined in duplicate by enzymelinked immunosorbent assay (ELISA) and a high-sensitivity MilliplexTM Multiplex kit (HSTCMAG-28SK-06, Millipore, Billerica, MA) per manufacturer's instructions. In patients, psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale-Anchored version (BPRS-A). Comparisons in cytokine levels between groups were performed using either t-tests for normally distributed variables or Wilcoxon rank-sum tests for nonnormally distributed variables. Correlations were computed using the Pearson's correlation coefficient. Results: The mean age was 36.6 years (SD = 11.7) in patients and 38.1 years (SD = 10.1) in controls. Twenty-four (72.3%) of 33 patients and 14 (60.1%) of the 23 healthy volunteers were male. Mean total BPRS score in patients was 28.6 (SD = 9.0). Mean TNF-α values were elevated in patients (6.47 pg/ml [SD = 3.1]) compared to healthy volunteers (3.76 pg/ml [SD = 2.5], P = .001). There were no statistically significant differences in levels between patients and controls in IL-2 (mean = 5.46 pg/ml [SD = 1.9] vs. 4.82 pg/ml [SD = 2.0], IL-6 (9.31 pg/m l[2.6] vs. 8.9 pg/ml [2.9]) and IL-8 (49.44 pg/ml [11.2] vs. 47.21 pg/ml [12.2]. Levels of IL-1β and IL-4 were not detected in more than 30% of the CSF samples; t...