Convergent neurobiological predictors of mood and anxiety symptoms and treatment response

Mbemba Jabbi, Charles Nemeroff

Research output: Contribution to journalArticle

Abstract

Introduction: Mood and anxiety disorders are leading contributors to the global burden of diseases. Comorbid mood and anxiety disorders have a lifetime prevalence of ~20% globally and increases the risk for suicide, a leading cause of death. Areas covered: In this review, authors highlight recent advances in the understanding of multilevel-neurobiological mechanisms for normal/pathological human affective-functioning. The authors then address the complex interplay between environmental-adversity and molecular-genetic mediators of brain correlates of affective-symptoms. The molecular focus is strategically limited to GTF2i, BDNF, and FKBP5 genes that are, respectively, involved in transcriptional-, neurodevelopmental- and neuroendocrine-pathway mediation of affective-functions. The importance of these genes is illustrated with studies of copy-number-variants, genome-wide association (GWAS), and candidate gene-sequence variant associations with disease etiology. Authors concluded by highlighting the predictive values of integrative neurobiological processing of gene-environment interactions for affective disorder symptom management. Expert opinion: Given the transcriptional, neurodevelopmental and neuroimmune relevance of GTF2i, BDNF, and FKBP5 genes, respectively, authors reviewed the putative roles of these genes in neurobiological mediation of adaptive affective-responses. Authors discussed the importance of studying gene-dosage effects in understanding affective disorder risk biology, and how such targeted neurogenetic studies could guide precision identification of novel pharmacotherapeutic targets and aid in prediction of treatment response.

Original languageEnglish (US)
Pages (from-to)587-597
Number of pages11
JournalExpert review of neurotherapeutics
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Keywords

  • Affect
  • anxiety
  • brain
  • depression
  • environment
  • function
  • genetics
  • prediction
  • structure
  • treatment

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Pharmacology (medical)

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