BDNF and COMT interaction in determining clinical presentation of first-episode psychosis: data from the PICOS-Veneto study

Background/Objectives: Despite a huge increase in reports on susceptibility genes, none of them has unambiguously been associated with psychosis. These disappointing results confirm the complexity of biological mechanisms leading to psychosis and suggest that genes might interact to determine a particular phenotype. Brain-derived neurotrophic factor (BDNF) and catechol-O-aminetransferase (COMT) genes are both involved in dopamine transmission pathways: Thus, it is meaningful to hypothesize that they may interact in the pathophysiology of psychosis. The present study aims to test whether BDNF x COMT interaction may influence specific patterns of clinical presentation at the onset.

Methods: The study was conducted in the broader framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite research conducted in Veneto (Italy) aiming at characterising first-episode psychosis patients. Psychopathology was collected using the Positive And Negative Syndrome Scale (PANSS) and genetic analyses were performed investigating BDNF rs6265 and COMT rs4680. Frequency analyses were performed with Chi-square or Fisher's exact test. Comparisons of continuous variables among genotype groups were performed by Kruskal-Wallis or Mann-Whitney test.

Results: Genotyping analyses for both BDNF and COMT have been performed on 216 patients and 511 controls. When considering the four types of gene interaction (COMT Val/Val x BDNF Val/Val, COMT Val/Val x BDNF Met carriers, COMT Met carriers x BDNF Val/Val, COMT Met carriers x BDNF Met carriers), psychopathology at baseline was significantly different for ‘conceptual disorganization’ item (p=0.004). Assuming a model of interaction comparing COMT Val/Val x BDNF Val/Val versus other combinations, we confirmed significant differences for the ‘conceptual disorganization’ item (p=0.012).

Discussion/Conclusions: Our study may help to clarify the role of genetic interaction in the clinical presentation of psychoses at the onset. Moreover, the perspective of a symptom-based approach is attractive because it may provide a model for studying the heterogeneity of psychoses, enhancing the ability to identify the underlying pathophysiology of the illness. This could also provide new suggestions about prognosis and treatment responsiveness and hopefully contribute to define new prevention strategies for psychosis and better treatment interventions, such as pharmacological and support therapies on the basis of the patient's genetic background.

Funding: Grants from Fondazione Cariverona to Prof. Tansella; from the Ministry of Health, Ricerca Sanitaria Finalizzata 2004 to Prof. Ruggeri; and from the Ministry of Health, Ricerca Sanitaria Finalizzata 2005 to Dr. Lasalvia.

Keywords: Knowledge transfer, genetic, psychosis.