Cognitive Impairments in Schizophrenia and Schizoaffective Disorder

Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
The Journal of nervous and mental disease (Impact Factor: 1.69). 04/2012; 200(4):316-22. DOI: 10.1097/NMD.0b013e31824cb359
Source: PubMed


The present study aimed to compare population-based familial samples of patients with schizophrenia (n = 218) and schizoaffective disorder (n = 62) and a healthy control group (n = 123). Patients with schizoaffective disorder outperformed patients with schizophrenia in verbal ability, processing speed, visual working memory, and verbal memory. When compared with controls, patients with schizoaffective disorder also had a generalized cognitive impairment. Adjusting for clinical characteristics removed significant differences between the patient groups. Irrespective of the diagnosis, patients with the most severe negative symptoms and highest dose of antipsychotics had the most severe cognitive impairments, whereas mood symptoms were not related to cognitive performance. In conclusion, people with schizoaffective disorder have severe cognitive impairments, but the impairments are milder than in schizophrenia. Mood symptoms may not explain the difference between the diagnostic groups in cognitive functions, but the difference may be related to differences in the severity of negative symptoms.

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    • "The effects of antipsychotic medication on cognitive functioning in schizophrenia are unclear. Higher doses of antipsychotic medication have been associated with poorer cognition in cross-sectional, naturalistic studies (Elie et al., 2010; Torniainen et al., 2012). In a metaanalysis of randomized controlled trials with relatively short followups (range 26–78 weeks) there were significant differences between the effects of different atypical antipsychotics on global cognition, and in general, antipsychotic medication enhanced cognition (Désaméricq et al., 2014). "
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    ABSTRACT: Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+.Neuropsychopharmacology Reviews advance online publication, 5 September 2012; doi:10.1038/npp.2012.125.
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