Abstract
Patients with schizophrenia are at an increased risk for the development of depression. Overlap in the symptoms and genetic risk factors between the two disorders suggests a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. Understanding these shared mechanisms will be important in informing the development of new treatments. Rodent models are powerful tools for understanding gene function as it relates to behavior. Examining rodent models relevant to both schizophrenia and depression reveals a number of common mechanisms. Current models which demonstrate endophenotypes of both schizophrenia and depression are reviewed here, including models of CUB and SUSHI multiple domains 1, PDZ and LIM domain 5, glutamate Delta 1 receptor, diabetic db/db mice, neuropeptide Y, disrupted in schizophrenia 1, and its interacting partners, reelin, maternal immune activation, and social isolation. Neurotransmission, brain connectivity, the immune system, the environment, and metabolism emerge as potential common mechanisms linking these models and potentially explaining comorbid depression in schizophrenia.
Highlights
Schizophrenia and depression are devastating mental illnesses that contribute substantially to the global burden of disease [1,2,3]
Depression has been reported during all stages of the course of schizophrenia [5,6,7,8], and depressive symptoms are associated with an increased risk of suicide [9, 10]
A genome wide association study (GWAS) of five major psychiatric disorders found that SNPs within chromosomal regions 3p21 and 10q24, and calcium channel subunit genes CACNA1C and CACNB2 were significantly associated with schizophrenia, depression, bipolar, attention deficit-hyperactivity (ADHD), and autism spectrum disorders (ASD) [35]
Summary
Schizophrenia and depression are devastating mental illnesses that contribute substantially to the global burden of disease [1,2,3]. Methodological differences in diagnosis and time course of evaluation mean that there is a wide variance of depressive symptoms reported by patients with schizophrenia in the literature, with prevalence rates as high as 61% [11]. The emergence of psychotic symptoms in depression, considered as a distinct clinical subtype of depression called psychotic depression or depression with psychotic features, is associated with increased severity of depressive symptoms [18, 19] This mutual relationship of risk between schizophrenia and depression suggests potential overlap in the pathophysiology and/or etiology of the two disorders. Low diagnostic reliability has led some to question the inclusion of schizoaffective disorder as a separate condition [21, 22] It remains unclear whether depressive symptoms should be considered as a symptom of schizophrenia, comorbid symptoms, or unrelated epiphenomena [23].
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