Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study.

OBJECTIVE: Although several magnetic resonance imaging (MRI) studies have been conducted in adults with obsessive-compulsive disorder (OCD), few studies have used voxel-based morphometry to examine brain structure, especially in psychotropic drug-naive pediatric patients. METHOD: MRI examinations of 37 psychotropic drug-naive pediatric OCD patients and 26 age- and sex-matched healthy volunteers were acquired on a 1.5 T MRI system, normalized to a customized template, and segmented with optimized voxel-based morphometry. RESULTS: Pediatric OCD patients had significantly more gray matter in regions predicted to differ a priori between groups, including the right and left putamen and orbital frontal cortex. Among patients, more gray matter in the left putamen and right lateral orbital frontal cortex correlated significantly with greater OCD symptom severity, but not with anxiety or depression. Manual region-of-interest measurements confirmed more gray matter in the orbital frontal cortex and putamen in patients compared to healthy volunteers. More anterior cingulate gray matter was evident among patients compared to healthy volunteers with regional volumetry but not with voxel-based morphometry. Regions of significantly less gray matter in OCD were confined to the occipital cortex and were not predicted a priori. CONCLUSIONS: Our results suggest that OCD is characterized by more gray matter in brain regions comprising cortical-striatal-thalamic-cortical circuits. These findings are consistent with functional neuroimaging studies reporting hypermetabolism and increased regional cerebral blood flow in striatal, anterior cingulate, and orbital frontal regions among OCD patients while in a resting state.

High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?

OBJECTIVE: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('high-normal' TSH compared with 'low-normal' TSH). DESIGN AND METHODS: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 microU/ml) as well as those with 'low-normal' TSH (0.40-1.99 microU/ml) were randomly assigned to receive either 25 or 50 microg T4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 microg T4 respectively and groups C and D (high-normal TSH) received 25 and 50 microg T4 respectively. Serum T4, tri-iodothyronine (T3), TSH, free thyroxine index, resin T3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. RESULTS: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77+/-0.55, after: 1.41+/-0.85 microU/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. CONCLUSIONS: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.