Lack of cortico-limbic coupling in bipolar disorder and schizophrenia during emotion regulation

R W Morris,M J Green,C S Weickert,P B Mitchell,A Sparks

doi:10.1038/tp.2012.16

Abstract

Bipolar disorder (BD) and schizophrenia (Sz) share dysfunction in prefrontal inhibitory brain systems, yet exhibit distinct forms of affective disturbance. We aimed to distinguish these disorders on the basis of differential activation in cortico-limbic pathways during voluntary emotion regulation. Patients with DSM-IV diagnosed Sz (12) or BD-I (13) and 15 healthy control (HC) participants performed a well-established emotion regulation task while undergoing functional magnetic resonance imaging. The task required participants to voluntarily upregulate or downregulate their subjective affect while viewing emotionally negative images or maintain their affective response as a comparison condition. In BD, abnormal overactivity (hyperactivation) occurred in the right ventrolateral prefrontal cortex (VLPFC) during up- and downregulation of negative affect, relative to HC. Among Sz, prefrontal hypoactivation of the right VLPFC occurred during downregulation (opposite to BD), whereas upregulation elicited hyperactivity in the right VLPFC similar to BD. Amygdala activity was significantly related to subjective negative affect in HC and BD, but not Sz. Furthermore, amygdala activity was inversely coupled with the activity in the left PFC during downregulation in HC (r=−0.76), while such coupling did not occur in BD or Sz. These preliminary results indicate that differential cortico-limbic activation can distinguish the clinical groups in line with affective disturbance: BD is characterized by ineffective cortical control over limbic regions during emotion regulation, while Sz is characterized by an apparent failure to engage cortical (hypofrontality) and limbic regions during downregulation.

Highlights

It is increasingly accepted that schizophrenia (Sz) and bipolar disorder (BD) share some genetic vulnerability,[1] comparably high heritability estimates[2,3] and neuropsychological dysfunction in common cognitive domains.[4,5,6] Consistent with these common traits, the neuroanatomical basis of these disorders shares various abnormalities in prefrontal, limbic and paralimbic brain regions.[7,8] Recently, the importance of determining the functional impact of these brain abnormalities has been proposed as a priority to improve diagnostic validity and identify new treatment targets.[9]
Nine of the Sz patients and five of the BD patients were being treated with atypical antipsychotic medication, and all BD patients were taking antidepressant medication
We examined cortico-limbic brain function during voluntary regulation of negative emotion in Sz, BD and healthy controls (HC) groups, using an established task known to activate prefrontal cortical regions concomitant with changes in amygdala activity during regulation of subjective affect

Summary

Introduction

It is increasingly accepted that schizophrenia (Sz) and bipolar disorder (BD) share some genetic vulnerability,[1] comparably high heritability estimates[2,3] and neuropsychological dysfunction in common cognitive domains.[4,5,6] Consistent with these common traits, the neuroanatomical basis of these disorders shares various abnormalities in prefrontal, limbic and paralimbic brain regions.[7,8] Recently, the importance of determining the functional impact of these brain abnormalities has been proposed as a priority to improve diagnostic validity and identify new treatment targets.[9] An important target may be the specific corticolimbic pathways that underlie the distinct forms of overt emotional dysfunction associated with each disorder. People with Sz have difficulty upregulating positive emotions,[10] while BD patients have inefficient strategies to downregulate negative affect, in association with higher levels of depression and anxiety.[11] In the present study, we sought to distinguish these related disorders on the basis of brain activation during the voluntary regulation of negative affect, as a means of differentiating cortico-limbic function in each disorder

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