Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder.

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

Effects of short-term cognitive-coping therapy on resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) tends to be treatment refractory. Recently, cognitive-coping therapy (CCT) for OCD is reported to be an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. Here, the effects of CCT on OCD and the resting-state brain function were investigated. METHODS: Fifty-nine OCD patients underwent CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Before and after a 4-week treatment, Yale-Brown obsessive-compulsive scale (Y-BOCS) was evaluated and resting-state functional magnetic resonance imaging (rs-fMRI) was scanned. RESULTS: Compared with the baseline, significant reduction of Y-BOCS scores was found after four-week treatment (p < .001) in groups of CCT and pCCT, not in pharmacotherapy. Post-treatment Y-BOCS scores of CCT group and pCCT group were not different, but significantly lower than that of pharmacotherapy group (p < .001). Compared with pretreatment, two clusters of brain regions with significant change in amplitude of low-frequency fluctuation (ALFF) were obtained in those who treated with CCT and pCCT, but not in those who received pharmacotherapy. The ALFF in cluster 1 (insula, putamen, and postcentral gyrus in left cerebrum) was decreased, while the ALFF in cluster 2 (occipital medial gyrus, occipital inferior gyrus, and lingual gyrus in right hemisphere) was increased after treatment (corrected p < .05). The changes of ALFF were correlated with the reduction of Y-BOCS score and were greater in remission than in nonremission. The reduction of the fear of negative events was correlated to the changes of ALFF of clusters and the reduction of Y-BOCS score. CONCLUSIONS: The effectiveness of CCT for OCD was related to the alteration of resting-state brain function-the brain plasticity. TRIAL REGISTRATION: ChiCTR-IPC-15005969.

Effectiveness of cognitive-coping therapy and alteration of resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT. PATIENTS AND METHODS: Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment. RESULTS: For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (P<0.001), but no group difference was observed. No differences in amplitude of low-frequency fluctuation (ALFF) values were found between CCT and pCCT either pre- or post-treatment. Compared to controls, ALFF in OCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected P<0.05). The ALFF in those regions was not significantly correlated to the severity of OCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared. LIMITATIONS: The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks. CONCLUSIONS: Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved.

Highly efficacious cognitive-coping therapy for overt or covert compulsions.

Pharmacotherapy and cognitive-behavioral therapy (CBT) present limitations when they are used to treat obsessive-compulsive disorder (OCD), a severe and debilitating psychiatric disorder. To search for more efficacious treatment, we investigated the effects of pharmacotherapy plus cognitive-coping therapy (pCCT) on adult OCD patients with overt or covert compulsions. Two hundred and fifteen OCD patients were randomized into pharmacotherapy plus psychological support (PPS, n=107) and pCCT (n=108). The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to measure severity of symptoms in the OCD patients. The Y-BOCS scores were significantly lower in pCCT than in PPS in both acute term (<3 months) and long-term follow-up. In pCCT, severity of symptoms was not different between those with covert compulsions and those with overt compulsions, but was significantly reduced at any post-treatment time-point. Y-BOCS scores in the two subtype compulsions were significantly lower in pCCT than in PPS at any post-treatpost-treatment time-point. Compared with PPS, effect size, response rate and remission rate were significantly higher in pCCT. Our findings corroborated with the hypothesis that pCCT could efficaciously treat OCD with overt compulsions or covert compulsion, suggesting that pCCT might be a potential option for adult OCD.

The relationship between single nucleotide polymorphisms in 5-HT2A signal transduction-related genes and the response efficacy to selective serotonin reuptake inhibitor treatments in Chinese patients with major depressive disorder.

OBJECTIVE: To explore the possible relationship between six single nucleotide polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gß3, rs2230739 of ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5-HT2A the signal transduction pathway) and the response efficacy to selective serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD) Chinese. METHODS: This study included 194 depressed patients to investigate the influence of 6 polymorphisms in 5-HT2A signal transduction-related genes on the efficacy of SSRIs assessed over 1 year. The efficacies of SSRIs on 194 MDD patients were evaluated in an 8-week open-trial study. Over 1 year, a follow-up study was completed for 174 of them to observe the long-term efficacy of SSRIs. The optimal-scaling regression analysis was used for testing the relationship between the different genotypes of five SNPs and the efficacy in MDD. RESULTS: It showed that the patients with rs5443TT and rs2230739GG have a relatively good efficacy in response to short-term SSRIs. We also found that good efficacy appeared in depressed patients with rs2230739GG in response to long-term SSRIs. CONCLUSIONS: It suggested that different genotypes of rs5443 and rs2230739 might influence the signal transduction pathways of second message and affect therapeutic efficacy.