Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.
BACKGROUND
Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD.


METHODS
The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34).


RESULTS
Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects.


CONCLUSIONS
The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.
Molecular Imaging Branch, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. dara.cannon@nuigalway.ie
Dara M
DM
Cannon
Masanori
M
Ichise
Denise
D
Rollis
Jacqueline M
JM
Klaver
Shilpa K
SK
Gandhi
Dennis S
DS
Charney
Husseini K
HK
Manji
Wayne C
WC
Drevets
D000293:Adolescent; D000328:Adult; D000814:Aniline Compounds / Q000378:metabolism; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D002250:Carbon Radioisotopes / Q000378:metabolism; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism; D012016:Reference Values; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides