Genetic variants associated with psychotic symptoms across psychiatric disorders

Stefania Boccia, Luigi Janiri, Marco Di Nicola, Marco Calabrò, Stefano Porcelli, Concetta Crisafulli, Diego Albani, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Vilma Mantovani, Julien Mendlewicz, Stefano Bonassi, Eduard Vieta, Alessandra Frustaci, Giuseppe Ducci, Stefano Landi, Antonello Bellomo, Roberto ColomboLaura Mandelli, Chiara Fabbri, Alessandro Serretti

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis. Methods: 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects. Results: five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster. Discussion: CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.
Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalNeuroscience Letters
Volume720
DOIs
Publication statusPublished - 2020

Keywords

  • CACNA1C
  • Cross-disorder risk
  • Depression
  • Genetics
  • Genome-Wide Association Study
  • Polymorphisms SNPs
  • Schizophrenia
  • Symptom clusters

Fingerprint

Dive into the research topics of 'Genetic variants associated with psychotic symptoms across psychiatric disorders'. Together they form a unique fingerprint.

Cite this