Dysfunctional brain circuitry in obsessive-compulsive disorder: source and coherence analysis of EEG rhythms.

BACKGROUND: Morphological and functional studies suggested involvement of several cortical and subcortical circuitries in patients with obsessive-compulsive disorder (OCD). The aim of the present study was to investigate networks involved in OCD pathophysiology, using power (coupling of EEG bands, low-resolution electromagnetic tomography-LORETA) and coherence analysis in drug-naïve patients. METHOD: EEG was obtained from 37 drug-naïve patients with OCD and 37 age- and sex-matched controls. Resting EEG was recorded from 29 scalp channels. Coupling (ratio and correlation) between low and high frequencies was analyzed on Fz. For each frequency band, LORETA current density distribution, intra-hemispheric and inter-hemispheric coherence analysis were computed. RESULTS: OCD had increased current density for delta in the insula and for beta in frontal, parietal and limbic lobes. OCD also had decreased inter-hemispheric coherence and reduced coupling between delta and beta frequencies. CONCLUSIONS: In OCD, increased frontal beta is consistent with previous evidence of frontal dysfunction. Hyperactivity of insular delta sources, together with rhythms decoupling and reduced interhemispheric alpha coherence are consistent with additional involvement of cortico-subcortical functional connections. Combined use of power and coherence analysis may provide functional measures on different levels of involvement of cortico-subcortical circuits in neuropsychiatric disorders.

Augmentation effect of repetitive transcranial magnetic stimulation over the orbitofrontal cortex in drug-resistant obsessive-compulsive disorder patients: a controlled investigation.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in the pathophysiology of obsessive-compulsive disorder (OCD); functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in the OFC, caudate nucleus, thalamus, and anterior cingulate gyrus. The goal of our single-blind study was to assess whether repetitive transcranial magnetic stimulation (rTMS) over the left OFC would influence OCD symptoms in drug-resistant patients. METHOD: Twenty-three consecutively admitted right-handed inpatients with DSM-IV-TR-diagnosed drug-resistant OCD were given rTMS (80% motor threshold, 1 Hz seconds per minute for 10 minutes every day for 15 days) to the left OFC parallel (active: n = 16) or perpendicular (sham: n = 7) to the scalp. The patients' OCD symptoms, mood, and anxiety were rated at baseline, at the end of treatment, and once every 2 weeks for 3 months after treatment. Data were gathered from June 2006 to November 2007. RESULTS: Considering changes in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores with 2-way analysis of variance for repeated measures for a total of 8 observations (before rTMS, after treatment, and every 2 weeks for 12 weeks' follow-up), we found significant reduction of YBOCS scores comparing active versus sham treatment for 10 weeks after the end of rTMS (P < .02), with loss of significance after 12 weeks (P < .06). We also found a reduction of anxiety and depression symptoms but not a significant difference in the 2 groups. CONCLUSIONS: Low-frequency rTMS of the left OFC produced significant but time-limited improvement in OCD patients compared to sham treatment.

Temperament and character in mood disorders: influence of DRD4, SERTPR, TPH and MAO-A polymorphisms.

Gene variants exert a complex range of effects on human normal and abnormal behavior. We previously reported the effect of gene variants in serotoninergic and dopaminergic pathways, in a range of clinical features in mood disorders, such as symptomathology, periodicity, social adjustment and treatment response. In this paper we hypothesized that the same gene variants could influence temperamental traits in mood disorders patients. We focused on genes of the serotoninergic and dopaminergic systems (dopamine receptor D4 gene, DRD4; serotonin transporter gene, promoter region SERTPR; tryptophan hydroxylase gene, TPH; monoamine oxidase A gene, MAO-A). Two hundred and seven euthymic subjects, affected by major depressive disorder (n=73) and bipolar disorder (n=134) were assessed by the Cloninger's Temperament and Character Inventory (TCI) and typed using PCR-based analyses. Possible stratification factors such as demographic, clinical and other temperamental factors were also taken into account. We observed that homozygosity for the short SERTPR allele was associated with low novelty-seeking scores (p=0.006) and genotypes containing the DRD4 long allele were marginally associated with low harm avoidance (p=0.05). Finally, the long MAO-A allele was associated with decreased persistence scores among females (p=0.006). Our observation of a pattern of influence on temperamental dimension exerted by serotonergic and dopaminergic genes suggests that the contribution of these polymorphisms to the clinical presentation of mood disorders could be mediated by an influence on personality differences.