Individual white matter bundle trajectories are associated with deep brain stimulation response in obsessive-compulsive disorder.

BACKGROUND: The ventral anterior limb of the internal capsule (vALIC) is a target for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD). Conventional surgical planning is based on anatomical landmarks. OBJECTIVE/HYPOTHESIS: We hypothesized that treatment response depends on the location of the active DBS contacts with respect to individual white matter bundle trajectories. This study thus aimed to elucidate whether vALIC DBS can benefit from bundle-specific targeting. METHODS: We performed tractography analysis of two fiber bundles, the anterior thalamic radiation (ATR) and the supero-lateral branch of the medial forebrain bundle (MFB), using diffusion-weighted magnetic resonance imaging (DWI) data. Twelve patients (10 females) who had received bilateral vALIC DBS for at least 12 months were included. We related the change in OCD symptom severity on the Yale-Brown obsessive-compulsive scale (Y-BOCS) between baseline and one-year follow-up with the distances from the active contacts to the ATR and MFB. We further analyzed the relation between treatment response and stimulation sites in standard anatomical space. RESULTS: We found that active stimulation of the vALIC closer to the MFB than the ATR was associated with better treatment outcome (p = 0.04; r2 = 0.34). In standard space, stimulation sites were largely overlapping between treatment (non)responders, suggesting response is independent of the anatomically defined electrode position. CONCLUSION: These findings suggest that vALIC DBS for OCD may benefit from MFB-specific implantation and highlight the importance of corticolimbic connections in OCD response to DBS. Prospective investigation is necessary to validate the clinical use of MFB targeting.

[Deep brain stimulation for psychiatric disorders]. / Diepe hersenstimulatie bij psychiatrische aandoeningen.

- Deep brain stimulation (DBS) corrects pathological activity of neuropsychiatric brain networks with high frequency current via implanted brain electrodes.- DBS is an effective and safe treatment for therapy-refractory obsessive-compulsive disorder and potentially also for therapy-refractory major depressive disorder.- Experimental psychiatric indications for DBS are Tourette syndrome, addiction, anorexia nervosa, post-traumatic stress disorder, autism and schizophrenia.- DBS influences brain networks that are relevant for a variety of psychiatric symptoms. Potentially, in the future this interventional technique may therefore be deployed more broadly.

[Transcranial magnetic stimulation in obsessive compulsive disorder: a systematic review]. / Systematische review: transcraniële magnetische stimulatie voor obsessieve-compulsieve stoornis.

BACKGROUND: Ten per cent of patients with obsessive-compulsive disorder (ocd) are resistant to treatment. For these patients, repetitive transcranial magnetic stimulation (rtms) may be an alternative form of treatment.
AIM: To clarify the effect and clinical application of rtms for treatment-resistant ocd.
METHOD: We searched the literature systematically and we discuss the relevant articles critically.
RESULTS: We included 17 randomised controlled trials (rcts) with 502 patients. The reported trials were small and heterogeneous. A small but consistent treatment effect was found for rtms (mean decrease y-bocs score 6.6 points) compared to placebo stimulation (mean decrease y-bocs score 2.4 points). However, the differences between the effects of rtms and the effects of placebo were often not statistically or clinically significant. The effect frequently disappeared within several weeks after ending rtms and the follow-up period was never longer than three months.
CONCLUSION: rtms is still not entirely suitable for inclusion in the regular treatment of resistant ocd. More information is needed about follow-up requirements and about the advisable length and intensity of the applied stimulation. Future developments may involve increasing the number of stimulation sessions, combining these with cognitive behavioral therapy and delivering a more personalised form of rtms.

[Deep brain stimulation in psychiatry]. / Diepe hersenstimulatie in de psychiatrie.

BACKGROUND: Deep brain stimulation (DBS) is now used regularly to treat therapy-refractory obsessive-compulsive disorders, and is being applied experimentally for refractory depression, Tourette syndrome, addiction, eating disorders, post-traumatic stress disorder, autism and schizophrenia. AIM: To review the effects and mechanisms of dbs and to consider the future opportunities for this type of treatment in psychiatry. METHOD: We reviewed the literature using PubMed. RESULTS:  DBS is effective and safe to use in the treatment of therapy-refractory OCD and has produced encouraging results in cases of refractory depression and Tourette syndrome. However, further investigations are needed with regard to the use of DBS for treating other psychiatric disorders. DBS influences brain networks that are relevant for a whole range of psychiatric symptoms. CONCLUSION:  DBS should always be considered as possible treatment for therapy-refractory OCD. DBS often leads to marked and rapid improvement in mood, anxiety, behaviour and other psychiatric symptoms, making it a promising intervention for a variety of refractory patient groups. The development of DBS for psychiatry will benefit from our increased knowledge about how specific brain networks relate to psychiatric dysfunctioning.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS: Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age

[Metabolic diseases in psychiatry]. / Stofwisselingsziekten binnen de psychiatrie.

Metabolic diseases can be associated with psychiatric symptoms. We present two case histories that demonstrate the importance of correctly diagnosing a metabolic disease as being the cause of psychiatric symptoms. We also discuss which symptoms or signals may indicate a metabolic disease.

GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up.

OBJECTIVE: To compare motor symptoms, cognition, mood, and behavior 3 years after deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) in advanced Parkinson disease (PD). METHODS: Patients with PD eligible for DBS were randomized to bilateral GPi DBS and bilateral STN DBS (1:1). The primary outcome measures were (1) improvement in motor symptoms in off-drug phase measured with the Unified Parkinson Disease Rating Scale (UPDRS) and (2) a composite score for cognitive, mood, and behavioral effects, and inability to complete follow-up at 36 months after surgery. RESULTS: Of the 128 patients enrolled, 90 were able to complete the 3-year follow-up. We found significantly more improvement of motor symptoms after STN DBS (median [interquartile range (IQR)] at 3 years, GPi 33 [23-41], STN 28 [20-36], p = 0.04). No between-group differences were observed on the composite score (GPi 83%, STN 86%). Secondary outcomes showed larger improvement in off-drug functioning in the AMC Linear Disability Scale score after STN DBS (mean ± SD, GPi 65.2 ± 20.1, STN 72.6 ± 18.0, p = 0.05). Medication was reduced more after STN DBS (median levodopa equivalent dose [IQR] at 3 years, GPi 1,060 [657-1,860], STN 605 [411-875], p < 0.001). No differences in adverse effects were recorded, apart from more reoperations to a different target after GPi DBS (GPi n = 8, STN n = 1). CONCLUSIONS: Off-drug phase motor symptoms and functioning improve more after STN DBS than after GPi DBS. No between-group differences were observed on a composite score for cognition, mood, and behavior, and the inability to participate in follow-up. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that STN DBS provides more off-phase motor improvement than GPi DBS, but with a similar risk for cognitive, mood, and behavioral complications.

Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.

Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus-pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS.

Cognitive-behavioural therapy augments the effects of deep brain stimulation in obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation (DBS) is a promising new treatment for patients with treatment-refractory obsessive-compulsive disorder (OCD). However, since most DBS patients only show a partial response, the treatment still needs to be improved. In this study we hypothesized that cognitive-behavioural therapy (CBT) could optimize the post-operative management in DBS and we evaluated the efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens. METHOD: A total of 16 patients with treatment-refractory OCD were treated with DBS targeted at the nucleus accumbens. After stabilization of decline in OCD symptoms, a standardized 24-week CBT treatment programme was added to DBS in an open-phase trial of 8 months. Changes in obsessive-compulsive, anxiety and depressive symptoms were evaluated using the Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression. RESULTS: Following the addition of CBT to DBS, a significant decrease in obsessive-compulsive symptoms was observed, but not in anxiety and depressive symptoms. In a subsequent double-blind phase, in which stimulation was discontinued, OCD symptoms returned to baseline (relapse) and anxiety and depressive symptoms worsened (rebound) compared with baseline. CONCLUSIONS: The results of this explorative study suggest that a combined treatment of accumbens DBS and CBT may be optimal for improving obsessive-compulsive symptoms in treatment-refractory OCD. However, a subsequent randomized controlled trial is necessary to draw firm conclusions. It seems that DBS results in affective changes that may be required to enable response prevention in CBT. This may indicate that DBS and CBT act as two complementary treatments.

Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS. METHOD: The COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery. RESULTS: After corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found. CONCLUSIONS: COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.