Substance use disorder (SUD) have negative consequences for affected individuals and society. Current treatments are moderately effective, partly due to the large heterogeneity in SUDs, including co-occurring psychopathology. A better understanding of the mechanisms underlying these frequently co-occurring psychiatric conditions is required to develop individualized treatments to increase treatment success rates. We systematically reviewed case-control studies investigating neurobiological differences measured using neuroimaging between participants with SUD only and participants with SUD and co-occurring psychiatric disorders. We searched articles in four databases. Inclusion criteria further existed of an ICD and/or DSM diagnoses based on interview assessment or Fagerström test for Nicotine Dependence scores ≥ 5. We hypothesised that co-occurring psychopathology could (1) amplify the neurobiological effects of SUD, (2) attenuate it, (3) have unique neurobiological effects, or (4) have no additional neurobiological effects.

From 10,076 unique records screened, we included a total of 26 articles investigating the effect of personality disorder cluster B and/or C (6), depression (4), PTSD (4), ADHD (4), schizophrenia (8), bipolar disorder (1) or anxiety disorders (1) on SUD. We found amplifying effects of co-occurring schizophrenia and personality disorder, unique effects of schizophrenia, ADHD and personality disorder, and attenuating or no effect of depression on SUD. Findings on PTSD were contradictory. In conclusion, different co-occurring psychiatric disorder have distinct effects on the neurobiology of SUD.