Neurobiology of schizophrenia: from outcome to pathophysiological insights

Excerpt

Besides positive and negative symptoms, the schizophrenia syndrome is characterized by various deficits in cognitive domains. This progressive neurocognitive impairment deeply impacts the lives of those afflicted and their families and is responsible for worsening of social abilities. In a large-scale naturalistic open-label study of first-episode schizophrenia patients, Segarra et al. [1] have proven that men have an earlier age of onset, poorer premorbid functioning and a higher presence of prodromal and negative symptoms compared with women. Women again show a better social outcome with more stabile relationships. Especially among women, acute stress precedes the onset of psychosis. However, at the 2-year follow-up under risperidone treatment, in both genders, the outcome improved significantly, which was more pronounced in men. However, in this study, non-deficit and chronic schizophrenia patients have been investigated. Réthelyi et al. [2] investigated cognitive functioning including working memory, attention, short-term memory, verbal memory and cognitive flexibility in these both groups and found that patients with deficit schizophrenia suffer from more severe neurocognitive impairment with cognitive flexibility being an independent predictor of outcome. The genetic background may influence cognitive deficits in these patients. Accordingly, Lennertz et al. [3] show the T allele of a promoter variant of the SHANK1 gene leading to impairments in working memory in schizophrenia patients and subjects at risk for psychosis. This is an interesting finding considering that SHANK1 knockout mice entail altered memory functions along with reduced dendritic spines and postsynaptic density, which also are features of schizophrenia. Cognitive test performance also serves as separator between schizophrenia and bipolar disorder. In this context, inhibitory control, which includes aspects of cognitive and behavioral control in processes of maintaining contextual information, may discriminate schizophrenia from affective disorders. Christodoulou et al. [4] detected more pronounced deficits of inhibitory control in schizophrenia patients with familial risk compared to patients with bipolar disorder. …