Details

Autor(en) / Beteiligte

• Taylor, Stephan
• Yao, Beier
• Tso, Ivy
• Welsh, Robert
• Petrou, Myria

Titel

50. Negative Affect, GABA, and the Medial Prefrontal Cortex in Psychosis

Ist Teil von

• Schizophrenia bulletin, 2017-03, Vol.43 (suppl_1), p.S26-S27

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2017

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Background: GABAergic abnormalities are the most consistent findings in the post-mortem literature in schizophrenia, but the functional significance of these findings is unknown. We have reported that changes in GABA tone (revealed by lorazepam challenge in a pharmaco-fMRI paradigm) in the medial prefrontal cortex (mPFC) occurred in the direction predicted by the post-mortem abnormalities and correlated with negative affects in patients and healthy control subjects. Negative affects (NA), including sensitivity to everyday stresses, are increasingly recognized as an important clinical dimension of psychosis, particularly in the early phases. To investigate links between NA and GABA, we examined GABA concentrations in patients with a first episode of psychosis (FEP) and attenuated psychosis syndrome (APS) using magnetic resonance spectroscopy (MRS). Methods: Subjects underwent MRI scanning on a 3T Philips Achieva scanner. Voxels (18 cc) were placed on the mPFC and midline occipital cortex (Occ), and MRS was performed with the point-resolved spectroscopy sequence (PRESS). Voxel data were analyzed for MEGA-PRESS spectroscopy with Gaussian curve fitting to the GABA peaks and LCModel software to determine peak concentrations of GABA+ (including signal from macromolecules) and creatinine (Cr), yielding GABA+/Cr ratios for analysis. All subjects completed the 9-item Psychological Stress Index (PSI-9), a validated measure of stress sensitivity and NA in psychosis. Results: We have completed a preliminary analysis of 28 subjects (FEP: n = 11, 21.8 ± 2.7 years; HC: n = 11, 20.5 ± 3.2 years; APS: n = 6, 20.2 ± 3.9 years). Of the patient subjects, 6 APS subjects and 1 FEP subject were off medications. Analysis with ANCOVA, with group as a factor and PSI-9 scores as a covariate, yielding a significant inverse relationship of PSI-9 scores with mPFC GABA concentration ( F [1,24] = 6.61, P  = .02), but no effect of group ( F [2,24] = 1.74, P  = .20). There were no effects of group or relationships with PSI-9 scores in the Occ voxel ( Ps > 0.2). We compared all subjects based on whether they were taking antipsychotic medications and found no differences for either voxel ( Ps > 0.5). There were no other significant relationships between GABA concentrations and clinical symptoms, cognitive variables (MCCB) or functional level. Conclusion: The data provide support for a relationship between GABA levels and NA, measured by the PSI-9 such that lower GABA concentrations in the mPFC are associated with higher levels of NA. The small sample size and preliminary nature of the data warrant caution. Nevertheless, given that potentiation of GABA activity with benzodiazepines reduces NA, the findings are of potential clinical relevance in understanding the role of GABA systems in affect regulation in psychosis.