Reversed diurnal variation in depression: associations with a differential antidepressant response, tryptophan: large neutral amino acid ratio and serotonin transporter polymorphisms

Psychol Med. 2005 Apr;35(4):511-7. doi: 10.1017/s0033291704003861.

Abstract

Background: Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported.

Method: A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline.

Results: Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter.

Conclusions: These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects*
  • Alleles
  • Amino Acids / blood*
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics
  • Circadian Rhythm / drug effects*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics
  • Female
  • Fluoxetine / therapeutic use*
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Nortriptyline / therapeutic use*
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Promoter Regions, Genetic
  • Serotonin Plasma Membrane Transport Proteins
  • Treatment Outcome
  • Tryptophan / blood*

Substances

  • Amino Acids
  • Antidepressive Agents
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Fluoxetine
  • Tryptophan
  • Nortriptyline