COMT but Not 5HTTLPR Gene Is Associated with Depression in First-Episode Psychosis: The Role of Stressful Life Events

Genes (Basel). 2023 Jan 29;14(2):350. doi: 10.3390/genes14020350.

Abstract

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis.

Keywords: 5-HTTLPR; COMT; depression; first-episode psychosis; stressful life events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechol O-Methyltransferase
  • Depression* / psychology
  • Genotype
  • Humans
  • Life Change Events
  • Psychotic Disorders*
  • Stress, Psychological / psychology

Substances

  • COMT protein, human
  • Catechol O-Methyltransferase

Grants and funding

This research was funded by the Ricerca Sanitaria Finalizzata 2004, Giunta Regionale del Veneto; by the Ricerca Sanitaria Finalizzata 2005, Giunta Regionale del Veneto; by the Fondazione Cariverona with the grant “Disabilita’ cognitiva e comportamentale nelle demenze e nelle psicosi. Sotto-obiettivo A.9. Basi morfofunzionali cognitive e genetiche delle psicosi maggiori: uno studio integrato longitudinale”; and by Ministero della Salute Ricerca Corrente 2020.