Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up.

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3-8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD.

Long-term electrical stimulation of bed nucleus of stria terminalis for obsessive-compulsive disorder.

We previously reported that bilateral electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) effectively reduces symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we used a linear mixed model to investigate the evolution of symptomatic and functional status of our patients (n=24) and examined if baseline variables could predict this evolution. Data were collected during routine, clinical psychiatric visits. Our analysis showed a long-term, sustained effect of electrical stimulation in the IC/BST. After a fast initial decline of OCD symptoms, these symptoms remain relatively stable. In addition, we found a strong ON/OFF effect of stimulation (e.g., due to battery depletion). Our data also show that it is not the surgical procedure but rather the electrical stimulation that drives the improvement in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. The Beck Depression Inventory (BDI) at baseline was the only predictor significantly related to the evolution of the Y-BOCS. A higher BDI at baseline seemed to be related to a smaller decrease of the Y-BOCS over time. In conclusion, electrical stimulation in the IC/BST has a fast and sustained effect on OCD and comorbid symptoms and functional status of patients.

Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder.

In 1998, we proposed deep brain stimulation as a last-resort treatment option for patients suffering from severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, 24 OCD patients were included in a long-term follow-up study to evaluate the effects of electrical stimulation in the anterior limbs of the internal capsule (ALIC) and bed nucleus of the stria terminalis (BST). We find that electrical stimulation in the ALIC/BST area is safe and significantly decreases obsessions, compulsions, and associated anxiety and depressive symptoms, and improves global functioning in a blinded crossover trial (n=17), after 4 years (n=18), and at last follow-up (up to 171 months, n=24). Moreover, our data indicate that BST may be a better stimulation target compared with ALIC to alleviate OCD symptoms. We conclude that electrical stimulation in BST is a promising therapeutic option for otherwise treatment-resistant OCD patients.

[Anxiety, obsessive-compulsive disorder and trauma in the DSM-5]. / Angst, obsessieve-compulsieve stoornis en trauma in de DSM-5.

BACKGROUND: The 12 anxiety disorders which were defined in the DSM-IV, have been increased to 27 disorders in the DSM-5. These 27 disorders have been subdivided into three chapters: 1. anxiety disorders, 2. obsessive-compulsive and related disorders (OCRD) and 3. trauma and stressor-related disorders. AIM: To describe the most important differences between the DSM-IV and DSM-5 classifications of the above-mentioned disorders. METHOD: Survey of the relevant literature. RESULTS: Within the chapter on anxiety disorders in DSM-5 the classifications of 'panic disorder' and 'agoraphobia' have been separated. In addition, DSM-5 allows the specification 'with panic attacks' to be applied to all psychiatric disorders. New additions to the group ocrd are: 'trichotillomania' and 'body dysmorphic disorder'. Also newly added to the group are the new classifications 'excoriation disorder' and 'hoarding disorder'. The DSM-IV group of adjustment disorders has been merged with the group of stress disorders. In accordance with the system adopted elsewhere in DSM-5, the disorders which are 'usually first diagnosed in infancy, childhood and adolescence' and which resemble the disorders defined in the three chapters have been added to these chapters. Two extra categories are defined in each of the three chapters. CONCLUSION: The three chapters in DSM-5 are little more than a re-arrangement of the disorders defined in DSM-IV. The revision has not led to any clarification of or insight into the relationship between and the etiology of these disorders.

Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder.

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

[Confusional arousal: a rare cause of self-injurious behaviour]. / Confusional arousal als zeldzame oorzaak van zelfverwonding.

Non-rapid eye movement (NREM) arousal sleep disorders (confusional arousal, somnambulism and sleep terror) are self-limiting and temporary phenomena which cannot be attributed to medical or psychiatric factors. However, very occasionally they can be the cause of unintentional injury to self or others. We describe the case of an 18-year-old who engaged in self-injurious behaviour while asleep. This behaviour could be attributed to confusional arousal.

[Disturbed sleep in children with ADHD: is there a place for melatonin as a treatment option?]. / Verstoorde slaap bij kinderen met ADHD: heeft melatonine een plaats in de behandeling?

BACKGROUND: Sleep disorders are common in children with ADHD and they are aggravated by treatment with stimulantia. We focus on treatment with melatonin and weigh up its efficacy and safety. AIM: To consider the evidence supporting the use of melatonin in the treatment of children with ADHD and to assess the efficacy and safety of such treatment. METHOD: We studied the literature using databases Embase, PubMed, PsycINFO and the Cochrane Library and the search terms 'ADHD', 'melatonin', 'insomnia', 'methylphenidate', 'side-effects', 'endocrinology'. RESULTS: 25-50% of children with ADHD reported disturbed sleep patterns particularly in the form of (chronic) sleep onset insomnia ((C)SOI). Currently available research results indicate that melatonin can be effective in the treatment of (C)SOI and, on the whole, is well tolerated. However, there is a lack of pharmaceutical preparations of melatonin that give details about their use for children and that give evidence-based guidelines about the dosage and timing of intake. Very little systematic research has been done into the possible impact of melatonin intake on puberty and the endocrine system. Therefore, treatment with melatonin in children with ADHD and (C)SOI is best reserved for children with persistent insomnia which is having a severe impact on daily functioning, particularly in cases where is an obvious phase-shift of the endogenous circadian rhythm. CONCLUSION: If indications are particularly strong there may be good reason to use melatonin to treat sleep disorders in children with ADHD. However, further research into the safety of melatonin is needed.

[Deep brain stimulation in a patient with ocd and the intensive pre- and post-operative psychiatric/psychotherapeutic follow-up. A case study]. / Klinische psychiatrische en psychotherapeutische begeleiding bij patiënte met diepe hersenstimulatie wegens obsessieve-compulsieve stoornis.

Deep brain stimulation (DBS) is a neurosurgical intervention carried out in meticulously selected patients with a therapy-resistant obsessive-compulsive disorder (OCD). We describe the pre- and post-operative psychiatric care given to a 51-year-old woman before, during and after treatment with deep brain stimulation. The psychiatric follow-up included an intensive search for the optimal stimulation parameters, and considerable attention was given to psycho-education, psychotherapy and counselling. The procedure resulted in a marked improvement in the patient's OCD and made it easier for the patient to re-construct a meaningful life.

[The decision-making process in obsessive compulsive disorder]. / Besluitvormingsproces bij obsessieve-compulsieve stoornis.

BACKGROUND: The extremely intrusive and repetitive nature of the symptoms of patients with obsessive-compulsive disorder (OCD) is suggestive of abnormalities in the decision-making process. This could explain why such patients realise how exaggerated and unreasonable their symptoms are, but time after time they become entrapped by them. AIM: To review the available research results relating to the underlying mechanisms of decision making and to link these to the characteristics of OCD. METHOD: We studied the literature on the decision-making process in OCD with the help of PubMed. RESULTS: There is a correlation between abnormalities in the decision-making process and dysfunction in the prefrontal cortex, more specifically in the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). The activity in these areas in the course of functional imaging is different in OCD patients and in healthy persons. Evaluation of abnormal decision-making in OCD patients performed with the help of the Iowa Gambling Task (IGT) is a possible predictor of the prognosis for pharmacological treatment. CONCLUSION: The concept of 'OCD as an abnormality in the decision-making process' generates new hypotheses concerning the etiology and pathophysiology of OCD. Abnormal decision-making may be an endophenotype, which could have important implications for treatment.

Treating primary insomnia: clinical effectiveness and predictors of outcomes on sleep, daytime function and health-related quality of life.

Primary insomnia, as defined by DSM-IV-TR, refers to a persistent sleep disturbance which is not connected to a current psychiatric or physical condition, but significantly impairs social and occupational functioning. This study explored the impact of Cognitive Behavioral Therapy for Insomnia (CBT-i) on sleep, daytime functioning and health-related quality of life (HRQoL). Next, we investigated which factors predicted positive treatment outcome by examining demographics, insomnia characteristics, baseline levels of daytime function, HRQoL, sleep-disruptive beliefs and psychological health on post-treatment sleep quality, daytime function and HRQoL. 138 consecutive primary insomnia patients completed questionnaires pre- and post-treatment and at 6 months follow-up. After CBT-i, robust clinical improvements were observed in sleep, daytime function and HRQoL, regardless of age, gender, type or duration of the complaint. Patients with pre-treatment severe insomnia, pronounced daytime impairment and low psychological well-being benefited most.

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. / Cognitieve gedragstherapie voor primaire insomnia: effectiviteit in een klinische setting.

BACKGROUND: The effectiveness of cognitive behavioural therapy for insomnia (cbt-i) has been demonstrated in randomised controlled trials (rct's) with primary insomnia patients and, more recently, with comorbid insomnia patients. The clinical impact of the treatment is mainly on sleep quality and the use of medication and to a lesser extent on daytime functioning. So far there have been very few studies of the effectiveness of cbt-i in clinical settings. AIM: To examine the effectiveness of cbt-i for primary insomnia via an uncontrolled prospective study in a clinical tertiary care setting. METHOD: We included 76 patients with primary insomnia, most of whom having been referred by their gp or medical specialist to the Leuven University Centre of Sleep, who followed a 6-week course of cbt-i as a group. Effects of cbt-i on primary and secondary outcome measures were studied. results cbt-i resulted in a significant improvement in all primary sleep variables such as sleep onset, sleep efficiency and sleep quality. The increase in total sleep time was less substantial, probably as a result of the specific sleep restriction guidelines. There was also a significant improvement on several secondary parameters, in particular dysfunctional cognitions, affective state, general health and use of medication. CONCLUSIONS: cbt-i has a significant impact on sleep quality, medication use and daytime functioning in primary insomniacs in a clinical tertiary care setting.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Applicants for stereotactic neurosurgery for psychiatric disorders: role of the Flemish advisory board.

OBJECTIVE: Research on stereotactic neurosurgery for psychiatric disorders (SNPD) is rapidly evolving. Knowledge on patients undergoing SNPD is of crucial importance. We describe applicants for SNPD and examine the necessity for a multidisciplinary advisory board. METHOD: Summary of the current practice of the Flemish advisory board (SNPD committee) and analysis of a questionnaire investigating the attitude of clinicians on SNPD. RESULTS: In 7 years, 91 applications were submitted, nine patients did not fulfill diagnostic criteria for OCD, 65 patients received a positive recommendation, 50 SNPD procedures were performed. The prevalence of SNPD in the current year in Belgium is 0.6/million inhabitants. Ninety-seven per cent of clinicians consider the expertise and advice of the SNPD committee essential for indication setting. Forty-four percent of clinicians consider referral of a patient for capsulotomy, 82% for electrical brain stimulation. CONCLUSION: Neurosurgery is exclusively considered for severe, treatment-refractory psychiatric disorders. Clinicians consider the SNPD committee essential in the decision-making process prior to intervention.

Behavioural and physiological effects of electrical stimulation in the nucleus accumbens: a review.

Electrical stimulation (ES) in the brain is becoming a new treatment option in patients with treatment-resistant obsessive-compulsive disorder (OCD). A possible brain target might be the nucleus accumbens (NACC). This review aims to summarise the behavioural and physiological effects of ES in the NACC in humans and in animals and to discuss these findings with regard to neuroanatomical, electrophysiological and behavioural insights. The results clearly demonstrate that ES in the NACC has an effect on reward, activity, fight-or-flight, exploratory behaviour and food intake, with evidence for only moderate physiological effects. Seizures were rarely observed. Finally, the results of ES studies in patients with treatment-resistant OCD and in animal models for OCD are promising.

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases.

OBJECTIVE: Investigation of deep brain stimulation (DBS) as a last-resort treatment alternative to capsulotomy in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Prospective single-case based design with evaluation of DBS impact on emotions, behaviour, personality traits and executive function in three patients with OCD. RESULTS: Two patients experienced sustained improvement of OCD symptoms with DBS. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) dropped 12 points and 23 points to baseline and Y-BOCS self-rating scale (Y-BOCS-SRS) and Profile of Mood States (POMS) for depression and tension decreased with increasing stimulation amplitude. Total Maladjustment Score on the Brief Psychiatric Rating Scale reduced with 44 and 59% to baseline. Reduction in psychopathology was sustained under continuous stimulation. No deleterious impact of DBS on neuropsychological testing or personality traits measured on a self-rated personality inventory was detected. CONCLUSION: These preliminary findings demonstrate that DBS may have important therapeutic benefits on psychopathology in OCD. No harmful side-effects were detected during follow-up (33/33/39 months, respectively).

Deep brain stimulation in treatment refractory obsessive compulsive disorder.

Obsessive-compulsive disorder is a worldwide psychiatric disorder with a lifetime prevalence of 2% and mainly characterized by obsessional ideas and compulsive behaviors and rituals. Many patients show improvement under cognitive behavioral and/or pharmacological treatment. A minority of patients is refractory to all available therapy and may benefit from capsulotomy. This study aims to investigate deep brain stimulation (DBS) as a last resort treatment alternative to capsulotomy in treatment refractory obsessive-compulsive disorder. Eight patients have been implanted bilaterally in the anterior limbs of the internal capsules with a quadripolar electrode. This paper presents the results of the first 4 operated patients. Acute deep brain stimulation displays an immediate improvement of the speech, mood, eye contact and motor function. Chronic deep brain stimulation improves significantly the obsessional and compulsive symptomatology in three out of the four patients. This study definitely needs replication, but the results are promising. Reversible deep brain stimulation may improve the symptomatology of treatment refractory OCD patients, without significant side effects.