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


METHODS
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.
Joyce
Peter R
PR
Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. peter.joyce@chmeds.ac.nz
Porter
Richard J
RJ
Mulder
Roger T
RT
Luty
Suzanne E
SE
McKenzie
Janice M
JM
Miller
Allison L
AL
Kennedy
Martin A
MA
D000328:Adult; D000339:Affect / Q000187:drug effects*; D000483:Alleles; D000596:Amino Acids / Q000097:blood*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009661:Nortriptyline / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood*
D000596:Amino Acids; D000928:Antidepressive Agents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D014364:Tryptophan; D009661:Nortriptyline