Glutamatergic function in a genetic high-risk group for psychosis: A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion.

Glutamatergic dysregulation is one of the leading theories regarding the pathoaetiolopy of schizophrenia. Meta-analysis of magnetic resonance spectroscopy studies in schizophrenia shows increased levels of glutamate and glutamine (Glx) in the medial frontal cortex and basal ganglia in clinical high-risk groups for psychosis and increased glutamine levels in the thalamus, but it is unclear if this is also the case in people at genetic high risk for psychosis. The aim of this study was to investigate glutamatergic function in the anterior cingulate cortex, striatum and thalamus in carriers of a genetic variant (22q11.2 deletion) associated with a high risk for psychosis. 53 volunteers (23 22q11.2 deletion carriers and 30 controls) underwent proton magnetic resonance spectroscopy imaging and neuropsychological assessments for prodromal psychotic symptoms, schizotypy, anxiety, depression and FSIQ. We did not find any difference between groups in Glx in the anterior cingulate cortex, striatum or thalamus (Glx: t(50)=-1.26, p = 0.21; U = 251, z = -0.7, p = 0.49; U = 316, z= -0.26, p = 0.79, respectively). No correlation was detected between Glx levels in any region and symptomatology or FSIQ. Our findings indicate that glutamatergic function is not altered in people at genetic high risk of psychosis due to the 22q11.2 deletion, which could suggest that this is not the mechanism underlying psychosis risk in 22q11.2 deletion carriers.

Evidence of disrupted prepulse inhibition in unaffected siblings of bipolar disorder patients.

BACKGROUND: Prepulse inhibition (PPI) of the startle response refers to a reduction in the response to a strong stimulus (pulse) if preceded shortly by a weak stimulus (prepulse). Disrupted PPI is thought to reflect abnormalities in the inhibitory control of information processing. Reduced PPI has been reported in mania, although it is not clear whether it represents a trait feature of bipolar disorder (BD). To address this issue, the present study examined whether disrupted PPI is present in individuals at high risk for BD. METHODS: Twenty-one remitted BD patients and 19 of their unaffected siblings were compared with 17 age- and gender-matched healthy volunteers on tests of acoustic startle reactivity and PPI of the startle response. RESULTS: There were no group differences in startle reactivity. Compared with healthy individuals, BD patients and their unaffected siblings showed lower PPI. In the patient group, no significant correlations were found between PPI and measures of symptom and disease severity or medication. CONCLUSIONS: This is the first study to report reduced PPI in remitted BD patients and their unaffected first-degree relatives. This finding, although in need of replication, suggests that PPI disruption may represent a trait deficit in BD associated with genetic predisposition.