title: Depressed patients have higher body temperature: 5-HT transporter long promoter region effects.
abstract: BACKGROUND
  Depression has been associated with a decrease in intracellular serotonin (5-HT) reuptake through its transporter, SERT. The 5-HT transporter long promoter region (5-HTTLPR) deletion in the SERT gene has also been associated with a decrease in 5-HT reuptake. Conversely, increases in extracellular 5-HT have been associated with increased temperature. It has not been established, however, whether body temperature in depressed patients is different from controls. Here, we hypothesized that temperature would be increased in depressed patients as well as in those with the 5-HTTLPR deletion.
  
  
  METHODS
  A strict oral temperature protocol employed single, cross-sectional, naturalistic time-of-day temperature measures in 125 subjects (46 normal controls, 79 outpatients with major depression). Controls and depressed patients were free of psychotropic medication and classified by the Structured Clinical Interview for Psychiatric Diagnoses. Eighty-one of the subjects (68 depressed, 13 normal) were additionally genotyped for 5-HTTLPR polymorphisms.
  
  
  RESULTS
  Depressed patients had a significantly higher uncorrected body temperature (mean +/- SD 98.38 +/- 0.61 degrees F) than controls (mean +/- SD 98.13 +/- 0.59 degrees F; F = 4.8, p = 0.03). An age (F = 14.09, p < 0.001) and time-of-day (11.4, p = 0.001) correction revealed a more robust (F = 14.02, p < 0.001) difference between depressed patients (mean +/- SD 98.44 +/- 0.55 degrees F) and controls (mean +/- SD 98.02 +/- 0.56 degrees F). When normalized for age and circadian differences between subjects, random, outpatient oral temperatures had a sensitivity of 63% and a specificity of 76% in identifying the depressed subjects from the controls. Independent of depression, subjects with the 5-HTTLPR deletion (short SERT allele) were warmer (mean +/- SD 98.33 +/- 0.65 degrees F) than those lacking the short allele on either chromosome (mean +/- SD 97.91 +/- 0.69 degrees F; F = 7.0, p = 0.01). However, the genotype did not explain the temperature differences between controls and depressed patients.
  
  
  CONCLUSIONS
  This is the first demonstration of an increased daytime body temperature in cases with major depression. Subjects with a corrected temperature above 98.3 degrees F were 2.6-fold more likely to be depressed. The results may strengthen the hypothesis of an inflammatory component of depression. In addition, the findings suggest a potential link between genetic differences in 5-HT transport and body temperature.
authors.affiliation: Department of Psychiatry and Health Behavior, Veterans Administration, The Medical College of Georgia, Augusta, GA 30912, USA. jeffreyr@mail.mcg.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Rausch
authors.forename: M E
authors.initials: ME
authors.lastname: Johnson
authors.forename: K M
authors.initials: KM
authors.lastname: Corley
authors.forename: H M
authors.initials: HM
authors.lastname: Hobby
authors.forename: N
authors.initials: N
authors.lastname: Shendarkar
authors.forename: Y
authors.initials: Y
authors.lastname: Fei
authors.forename: V
authors.initials: V
authors.lastname: Ganapathy
authors.forename: F H
authors.initials: FH
authors.lastname: Leibach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001831:Body Temperature / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D017931:DNA Primers / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008957:Models, Genetic; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins; D012895:Sleep, REM / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins