Analysis of magnetic resonance spectroscopy in patients with obsessive-compulsive disorder comorbid skin-picking disorder. / å¼ºè¿«ç—‡å ±ç— æŠ çš®éšœç¢æ‚£è€ ç£å ±æŒ¯æ³¢è°±åˆ†æž.

OBJECTIVES: To investigate the neurobiochemical characteristics of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) comorbid skin-picking disorder (SPD), and to provide reference for the pathophysiological basis for OCD. METHODS: We examined the levels of glutamate and other neurochemicals in ACC of 30 adult OCD patients (13 with comorbid SPD, 17 without SPD), using proton magnetic resonance spectroscopy (1H-MRS) at 3T. The clinical evaluation and the quantitative analysis of metabolites were carried out in the two groups. RESULTS: OCD patients with comorbid SPD showed significantly lower ACC glutamate than the patients without SPD (P=0.001). In all OCD patients, glutamate was negatively correlated with scores of Hamilton Anxiety Rating Scale (r=-0.55, P=0.002). Moreover, the ACC glutamate of female patients was correlated with the total score of Yale-Brown Obsessive Compulsive Scale (r=0.69, P=0.041) in the OCD with comorbid SPD patients. CONCLUSIONS: Alterations of the glutamate content in the ACC are involved in the pathophysiological process of OCD with comorbid SPD, which provides evidence for the study on the pathogenesis of OCD and SPD.

[Efficacy of fluvoxamine combined with extended-release methylphenidate on treatment-refractory obsessive-compulsive disorder].

OBJECTIVE: To observe the clinical efficacy of dopamine modulator methylphenidate (MPH) of extended-release formulations (MPH-ER) augmentation of ongoing fluvoxamine treatment in refractory obsessive-compulsive disorder (OCD) and its effects on patient's anxiety and sleep quality.
 Methods: A pilot randomized, placebo-controlled, and double-blind trial was conducted at an outpatient, single-center academic setting. Participants included 44 adults with serotonin reuptake inhibitor treatment-refractory OCD and they received a stable fluvoxamine pharmacotherapy with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores higher than 20. The 44 patients were randomly assigned into a study group and a control group, with 22 patiencs in each group. Fluvoxamine and MPH-ER were given to the study group, while fluvoxamine and placebo were given to the control group, with 8 weeks of the treatment course. Y-BOCS, Hamilton Anxiety Scale (HAMA) were used to assess the efficacy, Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality, and Treatment Emergent Symptom Scale (TESS) was used to evaluate the side effects. Data were analyzed in the intention-to-treat sample.
 Results: The improvement in the Y-BOCS total score, Y-BOCS obsession subscale score and HAMA score were more prominent in the study group than those in the control group (P<0.001). There was no significant difference in PSQI score and TESS score between the two groups. MPH-ER was well tolerated.
 Conclusion: Fluvoxamine combined with MPH-ER is effective in the treatment of refractory obsessive-compulsive disorder. It can improve anxiety and has no adverse effect on sleep quality.

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy.

BACKGROUND: Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS. METHODS: Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects. RESULTS: Significant reductions in N-acetylaspartate (NAA) and choline-containing Compound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group. CONCLUSIONS: Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.

Reduced sleep quality defines a subtype of obsessive-compulsive disorder with lower Glx levels in the resting thalamus and worse response inhibition.

BACKGROUND: The aim of this study was to investigate the differences between resting and active thalamic neurometabolite levels and inhibitory function in obsessive compulsive disorder (OCD) patients with poor sleep quality (PSQ was defined as Pittsburgh Sleep Quality Index >5 and sleep efficiency ≤85%) compared to OCD patients with good sleep quality (GSQ) and healthy controls (HCs), as well as the relationship of these indices to obsessive compulsive symptoms. METHODS: Functional magnetic resonance spectroscopy (fMRS) was used to measure resting and active thalamic neurometabolite levels in 72 subjects (20 HCs and 38 OCD patients included in study analysis). Response inhibition function was measured by the Go-Nogo task before and during MRS recording. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The symptoms of OCD, anxiety and depression were evaluated using relevant clinical scales. RESULTS: OCD patients exhibited significantly reduced Glx/Cr levels in the resting thalamus. The levels of resting thalamic Glu/Cr and Glx/Cr in OCD patients with PSQ were significantly lowest. OCD patients had significantly lower correct rates on Go tasks, higher error rates on Nogo tasks, and longer error average response times (EART) to the Nogo task. OCD patients with PSQ demonstrated the highest Nogo task error rate and the longest EART to Nogo task. Furthermore, PSQI scores exhibited negative correlations with Glu/Cr and Glx/Cr in the resting thalamus. CONCLUSION: OCD patients with PSQ demonstrated reduced levels of thalamic resting Glx and more pronounced response inhibitory function impairment. Aberrant neurometabolite levels in critical brain regions, coupled with heightened response inhibition function deficits, may be a neurobiological basis for the PSQ that OCD patients generally exhibit.

Glutamatergic neurotransmission is affected by low-frequency repetitive transcranial magnetic stimulation over the supplemental motor cortex of patients with obsessive-compulsive disorder.

OBJECTIVE: In obsessive-compulsive disorder (OCD), glutamatergic neurotransmission dysfunction played key roles in pathophysiology. The current research assessed changes of neurometabolites in the bilateral striatum of OCD patients receiving low-frequency repetitive transcranial magnetic stimulation (rTMS) using 1H proton magnetic resonance spectroscopy (1H-MRS). METHODS: 52 OCD patients were divided into rTMS treatment group (29) and the control group (medication only) (22). The levels of neurometabolites in the bilateral striatum of patients with OCD were measured using MRS before and after treatment. All participants were taking medication prior to the treatment and the process. RESULTS: Following rTMS treatment, Yale-Brown Obsessive-Compulsive Scale (YBOCS) score was significantly decreased in the rTMS group compared with the control group. Glutamate (Glu) and glutamate and glutamine complexes (Glx) in the bilateral striatum of the rTMS treatment response group increased significantly with the improvement of OCD. Glu in the bilateral striatum and Glx in the right striatum were positively correlated with compulsion after the treatment. CONCLUSIONS: The physiopathological mechanism of OCD may be related to the glutamatergic dysfunction, and the low-frequency repetitive transcranial magnetic stimulation applied to the supplementary motor area can improve OCD symptoms by modulating glutamatergic levels in the bilateral striatum of patients with OCD.

Direct changes of neurometabolic concentrations in the pregenual anterior cingulate cortex among obsessive-compulsive patients after repetitive transcranial magnetic stimulation treatment.

BACKGROUND AND AIM: Although Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising new noninvasive brain stimulation therapy, its underlying mechanisms of action remain unknown. OCD patients exhibit impaired response control and attention shifting, which is linked to some brain areas such as anterior cingulate cortex and basal ganglia. OCD patients also display altered neurometabolic concentrations in cortical cortical-striatal-thalamic-cortical (CSTC). In this study, we aimed to elucidate efficacy of rTMS treatment in alleviating related symptoms and pregenual anterior cingulate cortex (pACC) neurometabolites. METHODS: OCD patients were randomly divided into either drug (n = 23) or drug + rTMS (n = 29) groups, and those in the latter group subjected to 4-week rTMS treatment. All participants were visited twice, at baseline and follow-up after four weeks. During both visits, all patients were subjected to 1H-MRS, then Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Global Assessment Function (GAF) used to assess severity of obsessive-compulsive symptoms. We also evaluated synchronous anxiety and depression by Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). RESULTS: After 4 weeks of treatment, patients in the Drug + rTMS group displayed significantly lower Y-BOCS (p = 0.038), BDI (p = 0.009), HAM-D (p = 0.013), HAM-A (p = 0.012) scores than their counterparts in the Drug group. Conversely, patients in the Drug + rTMS group had significantly higher tNAA concentrations (p = 0.030) than those in the Drug group. Notably, the Drug + rTMS group exhibited higher, but insignificant Glu (p = 0.055) and Glx (p = 0.068) concentrations compared to the Drug group. Partial correlation analysis revealed a significant negative correlation between post HAM-A scores and 4-week change of pACC glutamate levels in the Drug + rTMS group (r = -0.434, p = 0.02). CONCLUSION: rTMS treatment is an efficacious treatment therapy for OCD, mainly by inducing changes in neurometabolites.

Predictors for 12-month long-term outcome in patients with obsessive-compulsive disorder: The influence of duration of untreated illness and age at onset.

BACKGROUND: It remains unknown whether the duration of untreated illness (DUI) may play a critical role in clinical improvement of patients with obsessive-compulsive disorder (OCD). Using a relatively large sample of subjects with OCD, this study investigated the potential impact of the DUI on patients' clinical course and long-term treatment response. METHODS: Two hundred and seven patients with OCD recruited by the OCD outpatient clinic of our university hospital participated in the study. The sample was divided into two groups according to the median DUI (DUI≤3 years and DUI >3 years). Patients were treated with selective serotonin reuptake inhibitors or venlafaxine for 48 weeks in open-label conditions. Treatment response and other clinical variables were analysed. RESULTS: The total sample showed a mean (SD) DUI of 4.07 (3.5) years, and the mean (SD) illness duration was 6.27 (6.5) years. More than half of the patients had not been treated before (56.5% for OCD). With a median of 3 years as cutoff DUI, response rates were found to be significantly higher in subjects with a short DUI (p < 0.001). Regression analyses showed that a short (≤3 years) DUI and later age at onset predicted better response and higher Y-BOCS scores percentage changes at the endpoint of 48 weeks (ß = -1.11, p = 0.003). In addition, there was no correlation between DUI and age of onset in the total patients (r = -0.13, p＞0.05). CONCLUSIONS: This preliminary study suggests associations between a shorter duration of untreated OCD and favourable long-term outcomes, and a longer DUI with a worse clinical course.

Reduced anterior cingulate glutamate of comorbid skin-picking disorder in adults with obsessive-compulsive disorder.

BACKGROUND: Obsessive Compulsive Disorder (OCD) is characterized by hyperactivity in a network of forebrain structures, including the anterior cingulate cortex (ACC). Convergent evidence suggests that glutamatergic dysfunction may contribute to the disorder. Skin picking disorder (SPD) was listed as one of the obsessive-compulsive and related disorders, which is often comorbid with OCD and share overlapping phenomenology and pathophysiology. However, potential confounding effects between the two diagnostic effects on neurotransmitter levels remain largely unexamined. METHODS: We examined the pregenual anterior cingulate cortex (pACC) glutamate and other neurochemicals in 62 subjects using a single-voxel acquisition 1H MRS at 3Tesla; of these, 47 subjects yielded usable measurements of both glutamate and glutamine and were included in the analysis (17 medicated with OCD alone, 13 medicated with comorbid OCD + SPD, 17 healthy control). RESULTS: OCD with comorbid SPD showed significantly lower pACC glutamate than in patients without SPD (p = 0.001) or control subjects (p = 0.035). OCD without SPD subjects showed pACC glutamate levels indistinguishable from controls (p = 0.501). In the OCD with SPD subjects, glutamate was correlated with Y-BOCS total score in female patients (n = 9, r = 0.69, p = 0.041). LIMITATIONS: The main limitation of the study was the cross-sectional data. Our patients were on SSRI medication which may have modified the effect of SPD and OCD interaction on glutamate activity. CONCLUSION: Our results suggest that alterations of the glutamatergic system may play an important role in the pathophysiology of a subgroup of OCD and reduced pACC glutamate may be a biomarker of a distinct subset of OCD patients.

Combined fluvoxamine and extended-release methylphenidate improved treatment response compared to fluvoxamine alone in patients with treatment-refractory obsessive-compulsive disorder: A randomized double-blind, placebo-controlled study.

More effective, tolerable interventions for treatment-refractory obsessive-compulsive disorder (OCD) are needed. Preliminary findings encourage optimism that methylphenidate augmentation may be of benefit in the treatment of OCD. To test modulator methylphenidate (MPH) of extended-release formulations (MPH-ER) a safe and effective add-on therapy for refractory OCD, a pilot randomized, placebo-controlled, double-blind trial was conducted at an outpatient, single-center academic setting. Participants included 44 adults with serotonin reuptake inhibitor (SRI) treatment-refractory OCD and receiving a stable fluvoxamine pharmacotherapy with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores higher than 20. Data were analyzed in the intention-to-treat sample. All subjects were randomized into two parallel groups to receive fluvoxamine (250 mg daily) plus MPH-ER (36 mg daily) or fluvoxamine (250 mg daily) plus identical placebo tablets under double-blind conditions and followed for 8 weeks. Forty-four patients (29 [66%] men), with a mean (SD) age of 24.7 (6) years participated; with a mean (SD) duration of episode 5.7 (3) were randomized and forty-one finished the trial. In the intention-to-treat analysis, the improvement in the Y-BOCS total score and Y-BOCS obsession subscale score was more prominent in the fluvoxamine and MPH-ER group compared with those receiving placebo (P < .001). Additionally, cumulative response rates were higher in the MPH-ER vs placebo groups (59% vs 5%; P  < .001). MPH-ER was well tolerated; No subjects dropped out due to side effects. In summary, combined treatment with MPH-ER demonstrated an enhanced clinical rate of response compared to placebo. Further trials should examine MPH-ER efficacy in a larger sample.