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Neuroplasticity and second messenger pathways in antidepressant efficacy: pharmacogenetic results from a prospective

Chiara Fabbri1, Concetta Crisafulli2, Raffaella Calati3

  • 1Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.

European Archives of Psychiatry and Clinical Neuroscience
|March 6, 2017
PubMed

Insights

This study replicated genetic findings for antidepressant response in treatment-resistant depression (TRD). Key genes like ZNF804A, CREB1, and CHL1 influence treatment outcomes and neuroplasticity.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Molecular Psychiatry

Background:

  • Antidepressant efficacy is influenced by genetic factors.
  • Understanding genetic modulators is crucial for treating major depressive disorder and treatment-resistant depression (TRD).

Purpose of the Study:

  • To replicate genetic associations with antidepressant response in an independent TRD sample.
  • To explore molecular pathways underlying antidepressant efficacy using pathway analysis.

Main Methods:

  • Genomic analysis of 50 tag SNPs in 14 genes related to neuroplasticity, monoamine, circadian rhythm, and transcription factor pathways.
  • Phenotyping based on response and remission to venlafaxine and escitalopram in 220 MDD patients.
  • Pathway analysis using KEGG database and cross-validation with the STAR*D sample.

Main Results:

  • Replicated associations for ZNF804A (response), CREB1 (remission), and CHL1 (reduced TRD risk).
  • Identified other CHL1 SNPs as potential predictors of TRD.
  • MAPK1 rs6928 SNP showed consistent association across all phenotypes; protein processing in endoplasmic reticulum pathway implicated.
  • Confirmed signals in CREB1, ZNF804A, and CHL1, highlighting their roles in synaptic plasticity and neural connectivity.

Conclusions:

  • Genetic variants in ZNF804A, CREB1, and CHL1 are confirmed predictors of antidepressant response and TRD risk.
  • MAPK1 and the endoplasmic reticulum pathway may play significant roles in antidepressant mechanisms.
  • These findings reinforce the importance of neuroplasticity and neural connectivity genes in depression treatment.
Keywords:
AntidepressantGeneNeuroplasticityPharmacogeneticsPolymorphismTreatment-resistant depression

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