4.4 Hippocampal Glutamate and Functional Connectivity as Biomarkers of Treatment Response to Antipsychotic Medication
Year: 2017
Type: conference-abstract
Abstract: Background: We previously reported elevated hippocampal regional cerebral blood flow (rCBF) in unmedicated patients with schizophrenia (SZ) and rCBF reduction associated with good treatment response to antipsychotic drug (APD). To characterize the pathophysiology of this pattern, we conducted a longitudinal study where hippocampal neurochemistry and function were measured before and after APD treatment. Methods: Unmedicated SZ were scanned before and after 6 weeks of treatment with risperidone and categorized as good (TR; n = 17) or poor (TPR; n = 17) responders based on a median split of treatment response (percentage change in the Brief Psychiatric Rating Scale psychosis score). Matched healthy controls (HC; n = 23) were scanned twice, 6 weeks apart. Resting-state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS; PRESS sequence) of the left (L) hippocampus were obtained at both time points. The fMRI preprocessing and analyses were conducted using the CONN toolbox in SPM8. The first eigenvariate of the blood oxygen level-dependent time series from an L hippocampal seed region was extracted and correlated with the time series from each of 14 individual network masks. MRS data were quantified in the time domain using jMRui. N-acetyl-aspartate, choline, and glutamate + glutamine (Glx) were quantified. Generalized linear mixed effects models with an identity link were employed to estimate the association between the dependent variables (metabolite/hippocampus to network connectivity values), Group, and Time. Additional analyses were performed to explore the relationship between altered neurochemical and functional connectivity patterns observed in SZ. Results: At baseline, Glx levels were significantly higher in TR compared to HC (P < .01). After treatment, TR, but not TPR, showed a significant decrease in Glx levels (P < .02). At baseline, the functional connectivity between the hippocampus and the executive network was significantly greater in TPR compared to HC. In TR, no change in hippocampus functional connectivity from baseline to Week 6 was observed. Likewise, in TNR, hippocampal Glx did not explain a significant proportion of the variance in the pattern of abnormal hippocampal connectivity to the executive network. Conclusion: Lack of relationship between altered glutamate levels and functional connectivity patterns in TR and TPR suggest independent pathophysiological mechanisms. Prior to treatment, hippocampal Glx and function connectivity are measures that could be leveraged to predict treatment response. Funding: This work was supported by grant R01 MH081014 and MH102951.
Source: Schizophrenia Bulletin
Institutions: University of Alabama at Birmingham, Auburn University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2598751105