Neuroimaging Studies in Patients With Mental Disorder and Co-occurring Substance Use Disorder: Summary of Findings

Abstract

Introduction: More than half of psychiatric patients have comorbid substance use disorder (dual diagnosis) and this rate, confirmed by many epidemiological studies, is substantially higher compared to general population. Combined operation of self-medication mechanisms, common etiological factors, and mutually causative influences most likely accounts for comorbidity, which, despite its clinical prevalence, remains underrepresented in psychiatric research, especially in terms of neuroimaging. The current paper attempts to review and discuss all existing methodologically sustainable structural and functional neuroimaging studies in comorbid subjects published in the last 20 years. Methods: Performing a systematic PubMed/MEDLINE, Web of Science, and Cochrane databases search with predefined key-words and selection criteria, 43 structural and functional neuroimaging studies were analyzed. Results: Although markedly inconsistent and confounded by a variety of sources, available data suggest that structural brain changes are slightly more pronounced, yet not qualitatively different in comorbid patients compared to non-comorbid ones. In schizophrenia (SZ) patients, somewhat greater gray matter reduction is seen in cingulate cortex, dorsolateral prefrontal and frontotemporal cortex, limbic structures (hippocampus), and basal ganglia (striatum). The magnitude of structural changes is positively correlated to duration and severity of substance use, but it is important to note that at least in the beginning of the disease, dual diagnosis subjects tend to show less brain abnormalities and better cognitive functioning than pure SZ ones suggesting lower preexisting neuropathological burden. When analysing neuroimaging findings in SZ and bipolar disorder subjects, dorsolateral prefrontal, cingular, and insular cortex emerge as common affected areas in both groups which might indicate a shared endophenotypic (i.e., transdiagnostic) disruption of brain networks involved in executive functioning, emotional processing, and social cognition, rendering affected individuals susceptible to both mental disorder and substance misuse. In patients with anxiety disorders and substance misuse, a common neuroimaging finding is reduced volume of limbic structures (n. accumbens, hippocampus and amygdala). Whether this is a neuropathological marker of common predisposition to specific behavioral symptoms and drug addiction or a result from neuroadaptation changes secondary to substance misuse is unknown. Future neuroimaging studies with larger samples, longitudinal design, and genetic subtyping are warranted to enhance current knowledge on comorbidity.

Keywords: anxiety disorders; comorbidity; mood disorders; neuroimaging studies; substance use disorders.