Alcohol Use Disorder and Schizophrenia or Schizoaffective Disorder.

ALCOHOL RESEARCH Current Reviews Alcohol Use Disorder and Schizophrenia or Schizoaffective Disorder Luke Archibald, Mary F. Brunette, Diana J. Wallin, and Alan I. Green Luke Archibald, M.D., is an assistant professor in the Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. Mary F. Brunette, M.D., is an associate professor in the Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. Diana J. Wallin, Ph.D., is a postdoctoral fellow in the Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. Alan I. Green, M.D., is the Raymond Sobel Professor of Psychiatry, a professor in the Department of Molecular and Systems Biology, and the chair of the Department of Psychiatry, Geisel School of Medicine at Dartmouth, as well as the director, Dartmouth Clinical and Translational Science Institute, Dartmouth College, Hanover, New Hampshire. Schizophrenia and schizoaffective disorder are schizophrenia spectrum disorders that cause significant disability. Among individuals who have schizophrenia or schizoaffective disorder, alcohol use disorder (AUD) is common, and it contributes to worse outcomes than for those who do not have co-occurring substance use disorder. Common neurobiological mechanisms, including dysfunction in brain reward circuitry, may explain the high rates of co-occurrence of schizophrenia and AUD or other substance use disorders. Optimal treatment combines pharmacologic intervention and other therapeutic modalities to address both the psychotic disorder and AUD. Further research on the etiology of these co-occurring disorders and on treatment of affected individuals is needed. KEY WORDS: addiction; alcohol; pharmacotherapy; schizoaffective disorder; schizophrenia Introduction Schizophrenia and schizoaffective disorder are heterogeneous psychotic disorders that often cause significant disability, with symptoms that include delusions, hallucinations, disorganization, and cognitive impairment.1 In schizoaffective disorder, the psychotic symptoms are present, along with mood episodes of depression or mania.2 People with these schizophrenia spectrum disorders have high rates of co-occurring substance use disorder, including alcohol use disorder (AUD). This article provides an updated review of the epidemiology, neurobiologic basis of co-occurrence, assessment, and treatment of people with co-occurring AUD and schizophrenia or schizoaffective disorder. Epidemiology The lifetime prevalence of schizophrenia is estimated to be about 1%.1 The lifetime prevalence of schizoaffective disorder is unknown, Schizophrenia or Schizoaffective Disorder | e1 given changes in diagnostic criteria and challenges in differentiating this disorder from other diagnoses, but it is believed to be less common than schizophrenia, with regional estimates between 0.3% and 1.1%.2,3 Individuals with these psychotic disorders have three times the risk of heavy alcohol use relative to the general population.4,5 One meta-analysis of individuals with schizophrenia found a lifetime prevalence of AUD of 24.3%.6 One American study reported that 36.4% of 404 participants had experienced AUD before their first episode of psychosis.7 In both the general U.S. population and among people with schizophrenia, AUD is associated with male gender and Caucasian race.7 For individuals who have schizophrenia, AUD is associated with depression, suicidality, medication nonadherence, chronic physical problems, homelessness, aggression, violence, incarceration, and high rates of hospitalization.7-10 Basis of Co-Occurrence The genetic risk for schizophrenia has been fairly well-established. Heritability is estimated to be 80% to 85% for schizophrenia.11 Studies of twins have been a way to isolate genetic risk from environmental risk. The concordance rate, the likelihood that a second twin will receive a diagnosis of schizophrenia after the first twin, has been estimated at 41% to 65% for monozygotic and 0% to 28% for dizygotic twins.11 In addition, multiple genetic determinants of risk for schizophrenia (especially within neural systems) may contribute to the risk for both psychosis and addiction. For disorders such as schizophrenia that stem from variation at multiple genetic loci, the various risk alleles can be summed together to determine a polygenic risk score. Strong associations between substance use disorder, including AUD, and the polygenic risk score for schizophrenia indicate that shared genetic liability may contribute to the co-occurrence of these disorders.12 Several polymorphisms (genetic variations) of the brain-derived neurotrophic factor (BDNF) protein correlate with co-occurring schizophrenia and alcohol dependence but not with alcohol dependence alone, suggesting that these polymorphisms may contribute to a specific e2 | Alcohol Research: Cu r re n t Re v ie ws | Vol 40 No 1 | 2019 vulnerability to these co-occurring disorders.13 Recently, a large genome-wide association study of individuals with alcohol dependence (diagnosed using the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders) revealed 17 traits, including schizophrenia, that had significant genetic correlations to alcohol dependence.14 These studies support the notion that certain genetic factors can lead to an increased risk for developing co-occurring schizophrenia and AUD. Several theories have emerged to explain the high prevalence of co-occurring schizophrenia and substance use disorder.8,15 Rosenthal first proposed the diathesis-stress model in 1970 to describe the combined interaction of a neurobiological vulnerability with an environmental vulnerability that leads to the development of schizophrenia.16 This theory is also called the “two-hit” model. For the development of schizophrenia and AUD, for example, the two hits could be a genetic risk for schizophrenia combined with alcohol drinking during adolescence. Although alcohol use in adolescence predicts future co-occurring mental health disorders and substance use disorder, adolescent exposure to alcohol was not found to be associated with the age of onset of psychosis.17 A variant of the two-hit model is the cumulative risk factor hypothesis, which posits that among people with schizophrenia, the increased risk for developing substance use disorder stems from the added risks of poor cognitive development, poor social functioning, effects of poverty, and poor social environments.1 Another theory explaining the high rate of substance use disorder among individuals who have schizophrenia is the self-medication hypothesis, which suggests that people use substances to find relief from symptoms or in an effort to decrease side effects that arise from antipsychotic treatments.18 Although clinically plausible, this theory has not been supported by research. Studies indicate that negative symptoms are not necessarily elevated in individuals with schizo (...truncated)