Although individuals with schizophrenia show a lifetime prevalence of 50% for suffering from a comorbid substance use disorder, substance abuse usually represents an exclusion criterion for studies on schizophrenia. This implies that surprisingly little is known about a large group of patients who are particularly difficult to treat. The aim of the present work is to provide a brief and non-exhaustive overview of the current knowledgebase about neurobiological and cognitive underpinnings for dual diagnosis schizophrenia patients. Studies published within the last 20 years were considered using computerized search engines. The focus was on nicotine, caffeine, alcohol, cannabis and cocaine being among the most common substances of abuse. All drugs of abuse target dopaminergic, glutamatergic and GABAergic transmission which are also involved in the pathophysiology of schizophrenia. Current literature suggests that neurocognitive function might be less disrupted in substance-abusing compared to non-abusing schizophrenia patients, but in particular the neuroimaging database on this topic is sparse. Detrimental effects on brain structure and function were shown for patients for whom alcohol is the main substance of abuse. It is as yet unclear whether this finding might be an artifact of age differences of patient subgroups with different substance abuse patterns. More research is warranted on the specific neurocognitive underpinnings of schizophrenia patients abusing distinct psychoactive substances. Treatment programs might either benefit from preserved cognitive function as a resource or specifically target cognitive impairment in different subgroups of addicted schizophrenia patients. 14 Elevated rates of substance use have been documented in non-psychotic firstdegree relatives of patients with schizophrenia, for example, for nicotine, alcohol and cannabis use. [15][16][17] In turn, alcohol and cannabis abuse have been associated with more frontal lobe and thalamus abnormities and increased risk for developing psychosis in individuals with high familial risk for developing schizophrenia. 18,19 As substance use disorder renders
METHODThe purpose of the present work is to provide a brief, but selective overview of theoretical views as well as neurobiological and cognitive correlates of DD schizophrenia. PubMed-and Web of Knowledgelisted studies involving patients with a DD of schizophrenia and substance (ab)use, published since 1990, were taken into account, with a focus on nicotine, caffeine, alcohol, cannabis and cocaine as the most common substances of abuse. During the search, the following key words and variations (e.g. as noun vs adjective) were used in variable combinations: 'dual diagnosis', 'schizophrenia', '(comorbid) substance use', 'structure', 'volume', 'function', '(f)MRI', 'cognition', 'neuropsychology' and 'executive'. These key words were also used in combination with the substances of interest 'nicotine/smoke', 'caffeine/coffee', 'alcohol', 'cannabis', 'cocaine'. Only studies explicitly focusing on...