GABA & Affective Dysregulation

Affective Dysregulation in Schizophrenia

Traditionally described as a ‘non-affective psychosis,’ emotional disturbance is an under-appreciated dimension of schizophrenia. We have conducted research showing how negative affect (e. g. distress, anxiety) is an important predictor of outcome, independent of cognition, negative symptoms, and positive symptoms (Tso et al, 2010). I have used brain mapping tools to demonstrate aberrant responses to salient stimuli in schizophrenia (e.g. Taylor et al, 2005), and synthesized this line of work with a meta-analytic study showing reduced recruitment of amygdala, anterior cingulate cortex and visual processing areas when schizophrenia patients process emotional stimuli (Taylor et al, 2012). Instead of recruiting secondary visual processing regions as controls, they tend to recruit brain circuits in posterior cortex, further downstream. Our group has also reported that aberrant activity in early visual processing areas predicts higher level functional impairment like social cognition, suggesting that widely distributed brain circuits need to be considered to understand the pathophysiology of the psychotic brain.

Negative affect predicts poor social functioning across diagnostic categories

Grove et al, Psychiatry Research 2016

The Fragile Brain: Stress Vulnerability, Negative Affect and GABAergic

Neurocircuits in Psychosis

In this theoretic review, we argue that the tendency of persons with schizophrenia to exhibit negative affects, such as the well-known vulnerability to even minor stresses, may reflect dysfunction of GABAergic systems. Find the article in Schizophrenia Bulletin

From Taylor, Grove, Ellingrod & Tso, 2009

Current projects in the lab exploring related topics:

Multi-Modal Assessment of GABA Function in Psychosis

Using converging MRI measures of GABA function (pharmacologic challenge with functional magnetic resonance imaging and magnetic resonance spectroscopy), this NIMH funded R01 is studying GABAergic systems across the psychosis spectrum, establishing critical foundation work for the development of pharmacologic and clinical targets to ameliorate the serious disturbances caused by psychosis syndromes. The R01 is listed in clinicaltrials.gov under NCT04004416

Meta-analysis of medial frontal cortex GABA MRS in psychosis and mood disoders

Led by Molly Simmonite, Ph.D.

Read our recent meta-analysis of GABA spectroscopy in psychosis and mood disoders. Although prior meta-analyses have been contradictory, focusing on the medial frontal cortex (MFC), we found reduced GABA concentration in schizophrenia patients in the mid MFC, and increased rostral MFC in bipolar disorders. Published online in Biological Psychiatry here.

Negative Affect and Neural Correlates of Cognitive Control in Psychosis Spectrum

Led by Takakuni Suzuki, Ph.D.

The project (K23 under review) investigates how a brain activity marker of cognitive control measured using electroencephalogram (EEG) may be different in individuals with psychosis spectrum disorder (such as schizophrenia and depression with psychosis). It will also examine how cognitive control relates to different forms of negative affect (such as sadness, anxiety, and distress) assessed in the laboratory as well as in people’s daily lives.

Affective dysregulation in schizophrenia patients experiencing catatonia: An electronic medical record survey

Led by Christopher Kline, M.D.

Searching through the health records of over 36,000 schizohrenia patients, those with diagnoses of catatonia (4.7%) were 1.7 and 1.8 times more likely to have diagnoses of anxiety or depression, respectively. Published in Schizophrenia Research.

Affective Dysregulation and Psychotic-like Experiences in a Longitudinal Cohort

Led by Lindsay A. Bornheimer, Ph.D.

Using data from the Michigan Longitudinal Study, we found that affective dysregulation in the mid-teen years predicted the occurrence of psychotic-like experiences 3 years later. See Lindsay's recent article in Schizophrenia Bulletin, published online 2 Feb 2022

Collaborators

Michigan Neural Distinctiveness Study (MiND)

Thad Polk, Ph.D.

The purpose of the Michigan Neural Distinctiveness (MiND) study is to investigate the relationship between cognitive abilities and brain function in younger and older adults. The goal is to shed light on the brain changes that underlie cognitive changes with age.

The relationship between MRS measures of GABA and inhibitory function measured using transcranial magnetic stimulation

Dissertation work of Dalia Khammash, Ph.D. (2022)

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