Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder

1. Arch Gen Psychiatry. 2011 Jul;68(7):732-41. doi:
10.1001/archgenpsychiatry.2011.16. Epub 2011 Mar 7.

Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients
with obsessive-compulsive disorder.

Berney A(1), Leyton M, Gravel P, Sibon I, Sookman D, Rosa Neto P, Diksic M, Nakai
A, Pinard G, Todorov C, Okazawa H, Blier P, Nordahl TE, Benkelfat C.

Author information:
(1)DERBH, Department of Psychiatry, McGill University, 1033 Pine Ave West,
Montreal, QC H3A 1A1, Canada.

CONTEXT: The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction
in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy
of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated
symptomatic state, however, remain to be fully characterized.
OBJECTIVE: To investigate brain regional 5-HT synthesis, as indexed by positron
emission tomography and the α-[(11)C]methyl-L-tryptophan trapping constant (K*),
in treatment-free adults meeting criteria for OCD.
DESIGN: Between-group comparison.
SETTING: Department of Psychiatry and Montreal Neurological Institute, McGill
University, and Department of Psychology, McGill University Health Centre,
Quebec, Canada.
PARTICIPANTS: Twenty-one medication-free patients with OCD (15 men with a mean
[SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1]
years) and 21 healthy controls matched for age and sex (15 men with a mean [SD]
age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years).
Main Outcome Measure The α-[(11)C]methyl-L-tryptophan brain trapping constant K*,
which was analyzed with Statistical Parametric Mapping (SPM8) and with
proportional normalization (extent threshold of 100 voxels with a peak threshold
of P ≤ .005).
RESULTS: Compared with healthy controls, the patients with OCD exhibited
significantly greater α-[(11)C]methyl-L-tryptophan trapping in the right
hippocampus and left temporal gyrus (Brodmann area 20). In the larger subsample
of all men, these same differences were also evident, as well as higher K* values
in the caudate nucleus. Individual differences in symptom severity correlated
positively with K* values sampled from the caudate and temporal lobe of the
patients with OCD, respectively. There were no regions where the patients
exhibited abnormally low K* values. Volumetric analyses found no morphometric
alterations that would account for the group differences.
CONCLUSION: The results support previous reports of greater striatal and temporal
lobe activity in patients with OCD than in healthy controls and suggest that
these disturbances include a serotonergic component. Previously reported glucose
metabolic disturbances in OCD involving the orbitofrontal and cingulate cortices,
in comparison, might reflect postsynaptic changes in the serotonergic system.

DOI: 10.1001/archgenpsychiatry.2011.16
PMCID: PMC3677917
PMID: 21383250 [Indexed for MEDLINE]

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