Family Caregivers' Perspectives on Challenges and Support Needs in Hospital-Based Palliative Care for Persons Living With Dementia.

Individuals with schizophrenia are particularly vulnerable to substance use disorders (SUD), with approximately 41 % affected () compared to 17 % of the general population (). Comorbid SUD are consistently correlated with a host of negative outcomes, including more severe positive symptoms, increased hospitalizations, and increased mortality (; ). It remains a largely open question as to why individuals with schizophrenia are especially vulnerable to addiction. One theory proposes that common factors, such as shared genetic effects, jointly increase risk for both schizophrenia and SUD (), and a number of family and genome-wide association studies support this hypothesis (; ). Genetic effects may manifest in variations in brain structure phenotypes, which have been consistently observed independently in both schizophrenia and SUD (, ; ); however, to our knowledge, no studies have identified how genetic effects that are between schizophrenia and SUD may impact brain structure, which could provide a possible mechanism for their comorbidity. The aims of the present study, therefore, are to 1) quantify shared genetic effects between schizophrenia and SUD, and 2) assess if those shared genetic effects are mediated by shared genetic effects on brain structure phenotypes. There is strong evidence for genetic effects on both schizophrenia and substance use individually. The heritability of schizophrenia is estimated at around 80 % (; ), and SUD is estimated at 40–70 % (; ), with some variation depending on the type of SUD and severity of use. There is also strong evidence in support of shared genetic effects between schizophrenia and SUD, with findings of a two- to three-fold increased risk for any SUD among individuals at genetic risk for psychosis based on family history (; ; ), and findings are similar for individual substances including alcohol use disorders (AUD), cannabis use disorders (CUD) and nicotine dependence (; ; ). Convergent evidence is also available from genome-wide association studies (GWAS), which have reported evidence for shared genetic effects between schizophrenia and alcohol, cannabis and tobacco use (; ; ; ). Individuals with schizophrenia tend to have reductions in many brain structure phenotypes as well as increased variability in ventricular volumes compared to individuals without any psychiatric diagnoses (; ). The areas with the largest differences in grey matter volume include the frontal lobe, prefrontal cortex, hippocampus, fusiform gyrus, superior temporal gyrus, and insula (). It is difficult to determine from such case-control study designs what is an effect of genetic risk, an effect of environmental risk, or a consequence of the diagnosis; therefore, family studies and genome-wide designs are necessary. Such studies have found that those at genetic risk for schizophrenia tend to have decreased volume in some of the same structures identified in individuals with schizophrenia, including total grey matter volume, frontal lobe structure volumes, parahippocampal gyrus volume, thalamic volume, and hippocampal volume (; ; ). Findings from genome-wide approaches are more mixed (; ), potentially because genome-wide approaches capture less of the variance associated with genetic effects than family studies (). A substantial body of work has also reported on structural brain differences that occur in individuals with problematic use of substances, including alcohol, cannabis, and tobacco () but fewer studies are available to disentangle genetic effects and effects of the substance use itself. There is some evidence for volumetric differences in amygdala and cerebellar volumes in relatives of individuals with AUD compared to those without a family history (; , ; ), and mixed evidence for differences in hippocampal volume (; ).