Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task.

A deficit in task-related functional connectivity modulation from electroencephalogram (EEG) has been described in schizophrenia. The use of measures of neuronal connectivity as an intermediate phenotype may allow identifying genetic factors involved in these deficits, and therefore, establishing underlying pathophysiological mechanisms. Genes involved in neuronal excitability and previously associated with the risk for schizophrenia may be adequate candidates in relation to functional connectivity alterations in schizophrenia. The objective was to study the association of two genes of voltage-gated ion channels (CACNA1C and KCNH2) with the functional modulation of the cortical networks measured with EEG and graph-theory parameter during a cognitive task, both in individuals with schizophrenia and healthy controls. Both CACNA1C (rs1006737) and KCNH2 (rs3800779) were genotyped in 101 controls and 50 schizophrenia patients. Small-world index (SW) was calculated from EEG recorded during an odd-ball task in two different temporal windows (pre-stimulus and response). Modulation was defined as the difference in SW between both windows. Genetic, group and their interaction effects on SW in the pre-stimulus window and in modulation were evaluated using ANOVA. The CACNA1C genotype was not associated with SW properties. KCNH2 was significantly associated with SW modulation. Healthy subjects showed a positive SW modulation irrespective of the KCNH2 genotype, whereas within patients allele-related differences were observed. Patients carrying the KCNH2 risk allele (A) presented a negative SW modulation and non-carriers showed SW modulation similar to the healthy subjects. Our data suggest that KCNH2 genotype contributes to the efficient modulation of brain electrophysiological activity during a cognitive task in schizophrenia patients.

Correlates of neurocognitive functions in individuals at ultra-high risk for psychosis - A 6-month follow-up study.

Cognitive deficits are evident at the prodromal phase of psychosis. It has been noted that brain-derived neurotrophic factor (BDNF) is correlated with cognition in both preclinical and clinical studies. However, to our knowledge, no study has evaluated blood BDNF levels and their association with cognitive impairment in individuals at ultra-high risk for psychosis (UHR). We included 13 individuals at UHR and 30 healthy controls (HC) matched by sex, age, and educational level. Plasma BDNF levels were measured at baseline and 6 months. Neurocognitive functions (executive functions, speed of processing, verbal learning and memory, working memory) were examined at 6 months. Regression analyses were conducted to examine the relationship between BDNF levels and cognitive performance. BDNF levels were lower in UHR group than in HC group both at baseline and at 6 months (P = 0.001, and P = 0.007, respectively). There were no associations between plasma BDNF levels and all of the cognitive domains in both groups. Our findings showed that peripheral BDNF levels were not related to cognitive deficits in UHR and HC groups while the lower BDNF level in the former persisted up to 6 months. Further research is needed in a large sample.