Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors.

METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1).

RESULTS: Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age.

CONCLUSIONS: Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance.