Familial psychosis risk linked to prefrontal dopamine dysfunction

By Stephanie Leveene, medwireNews Reporter

People at familial risk for psychosis have attenuated dopamine stress modulation in the ventromedial prefrontal cortex (vmPFC), according to a recent in vivo imaging study.

As Inez Myin-Germeys (Maastricht University School for Mental Health and Neuroscience, The Netherlands) and colleagues write in Schizophrenia Bulletin, these results are preliminary but indicate that "there is an urgent need for further human in vivo studies aimed at clarifying mechanisms of pathophysiological dopamine communication between cortical and subcortical brain regions in the context of psychosis."

Fourteen healthy individuals who had first-degree relatives with a psychotic disorder and 12 matched controls were assessed for frequency of psychotic symptoms via a self-report questionnaire. Psychosocial stress was induced during a positron emission tomography (PET) scan and the dopamine D_2/3 PET radioligand [¹⁸F] fallypride was used to measure in vivo dopamine release in the vmPFC.

The investigators found a differential association between task-induced dopamine activity and the experience of stress in the vmPFC in the relatives group versus the controls group. Greater levels of subjectively rated stress were linked to an increased intensity of psychotic experiences, an effect that was especially pronounced in the relatives group. The authors note that this matches "previously reported associations between abnormal dopamine reactivity and increased stress reactivity in the daily life of subjects at familial risk of developing psychosis."

These results emphasize the regulatory role that vmPFC dopamine neurotransmission has in the human stress response, says the team. The vmPFC is linked to self-control, regulation of emotions, and impulse control. People with damaged vmPFCs often have a hard time interpreting emotional and social cues and may overreact to social stress.

As all of the individuals/people in the relatives group were healthy, "future investigations of unmedicated patients and medication-naive subjects with at-risk mental states are therefore required to further clarify the role of attenuated prefrontal dopamine signaling in the etiology of psychosis," say the authors. They also add that, "our results do not imply causality, and the specific function of each brain region in the human stress response remains an important subject for further investigation."

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