Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation.

BACKGROUND: This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline. METHODS: 110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life. RESULTS: There were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson's Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02). CONCLUSIONS: This study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms. TRIAL REGISTRATION NUMBER: NTR5809.

Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.

Efficacy and quality of life after 6-9 years of deep brain stimulation for depression.

BACKGROUND: Given the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL). OBJECTIVE: To study the effectiveness and QOL up to nine years after the DBS surgery. METHODS: We treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6-9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental). RESULTS: Intention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains. CONCLUSION: This study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.

Augmenting neurocognitive remediation therapy to Preventive Cognitive Therapy for partially remitted depressed patients: protocol of a pragmatic multicentre randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial remission of MDD) are especially at risk for a return to a depressive episode within an average of 4 months. Simultaneously, partial remission of MDD is associated with work and (psycho)social impairment and a lower quality of life. Brief psychological interventions such as preventive cognitive therapy (PCT) can reduce depressive symptoms or relapse for patients in partial remission, although achieving full remission with treatment is still a clinical challenge. Treatment might be more effective if cognitive functioning of patients is targeted as well since cognitive problems are the most persisting symptom in partial remission and predict poor treatment response and worse functioning. Studies show that cognitive functioning of patients with (remitted) MDD can be improved by online neurocognitive remediation therapy (oNCRT). Augmenting oNCRT to PCT might improve treatment effects for these patients by strengthening their cognitive functioning alongside a psychological intervention. METHODS AND ANALYSIS: This study will examine the effectiveness of augmenting oNCRT to PCT in a pragmatic national multicentre superiority randomised controlled trial. We will include 115 adults partially remitted from MDD with subsyndromal depressive symptoms defined as a Hamilton Depression Rating Scale score between 8 and 15. Participants will be randomly allocated to PCT with oNCRT, or PCT only. Primary outcome measure is the effect on depressive symptomatology over 1 year. Secondary outcomes include time to relapse, cognitive functioning, quality of life and healthcare costs. This first dual approach study of augmenting oNCRT to PCT might facilitate full remission in partially remitted individuals as well as prevent relapse over time. ETHICS AND DISSEMINATION: Ethical approval was obtained by Academic Medical Center, Amsterdam. Outcomes will be made publicly available. TRIAL REGISTRATION NUMBER: NL9582.

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use.

BACKGROUND: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. AIMS: We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. METHOD: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. RESULTS: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. CONCLUSIONS: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study.

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.

Deep brain stimulation response in obsessive-compulsive disorder is associated with preoperative nucleus accumbens volume.

BACKGROUND: Deep brain stimulation (DBS) is a new treatment option for patients with therapy-resistant obsessive-compulsive disorder (OCD). Approximately 60% of patients benefit from DBS, which might be improved if a biomarker could identify patients who are likely to respond. Therefore, we evaluated the use of preoperative structural magnetic resonance imaging (MRI) in predicting treatment outcome for OCD patients on the group- and individual-level. METHODS: In this retrospective study, we analyzed preoperative MRI data of a large cohort of patients who received DBS for OCD (n = 57). We used voxel-based morphometry to investigate whether grey matter (GM) or white matter (WM) volume surrounding the DBS electrode (nucleus accumbens (NAc), anterior thalamic radiation), and whole-brain GM/WM volume were associated with OCD severity and response status at 12-month follow-up. In addition, we performed machine learning analyses to predict treatment outcome at an individual-level and evaluated its performance using cross-validation. RESULTS: Larger preoperative left NAc volume was associated with lower OCD severity at 12-month follow-up (pFWE < 0.05). None of the individual-level regression/classification analyses exceeded chance-level performance. CONCLUSIONS: These results provide evidence that patients with larger NAc volumes show a better response to DBS, indicating that DBS success is partly determined by individual differences in brain anatomy. However, the results also indicate that structural MRI data alone does not provide sufficient information to guide clinical decision making at an individual level yet.

Genetic correlates of socio-economic status influence the pattern of shared heritability across mental health traits.

Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic factors across mental health traits. However, mental health is also genetically correlated with socio-economic status (SES), and it is therefore important to investigate and disentangle the genetic relationship between mental health and SES. We used summary statistics from large genome-wide association studies (average N ~ 160,000) to estimate the genetic overlap across nine psychiatric disorders and seven substance use traits and explored the genetic influence of three different indicators of SES. Using genomic structural equation modelling, we show significant changes in patterns of genetic correlations after partialling out SES-associated genetic variation. Our approach allows the separation of disease-specific genetic variation and genetic variation shared with SES, thereby improving our understanding of the genetic architecture of mental health.

Genomic relationships across psychiatric disorders including substance use disorders.

BACKGROUND: A recent study investigated the genetic associations and latent genetic structure among eight psychiatric disorders using findings from genome-wide association studies (GWASs). No data from substance use disorders were included, while these represent an important category of mental disorders and could influence the latent genetic structure. We extended the original paper by recreating the genetic relationship matrix, graph, and latent genetic factor structure, including additional data from substance use disorders. METHODS: We used GWAS summary statistics of 11 psychiatric disorders, including alcohol dependence, nicotine dependence, and cannabis use disorder. We estimated genetic correlations between all traits in Linkage Disequilibrium-Score Regression. A graph was created to illustrate the network of genetic correlations. We then used the genetic relationships to model a latent genetic factor structure. RESULTS: Alcohol and nicotine dependence showed significant genetic correlations with several other psychiatric disorders, including ADHD, schizophrenia, and major depression. Cannabis use disorder was only significantly associated with ADHD. The addition of substance use disorders resulted in some changes in the latent structure of the factor model when compared to the original model including eight disorders. All substance use disorders contributed mostly to Factor 3, a heterogeneous factor with also loadings from ADHD, major depression, Autism Spectrum Disorders, and Tourette Syndrome. CONCLUSIONS: Alcohol and nicotine dependence show widespread genetic correlations with other psychiatric disorders. Including substance use disorders in the factor analysis results in some changes in the underlying genetic factor structure. Given the instability of such models, identified structures should be interpreted with caution.

Deep brain stimulation versus ablative surgery for treatment-refractory obsessive-compulsive disorder: A meta-analysis.

OBJECTIVE: Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation. METHODS: We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta-analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and the responder rate (≥35% reduction in Y-BOCS score). RESULTS: With responder rates of 48% and 53% after 12-16 months and 56% and 57% at last follow-up for ABL and DBS, respectively, and large effect sizes in the reduction in Y-BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta-regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS. CONCLUSION: This meta-analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.

Bidirectional effects between loneliness, smoking and alcohol use: evidence from a Mendelian randomization study.

BACKGROUND AND AIMS: Loneliness is associated with cigarette smoking and problematic alcohol use. Observational evidence suggests these associations arise because loneliness increases substance use; however, there is potential for reverse causation (problematic drinking damages social networks, leading to loneliness). With conventional epidemiological methods, controlling for (residual) confounding and reverse causality is difficult. This study applied Mendelian randomization (MR) to assess bidirectional causal effects among loneliness, smoking behaviour and alcohol (mis)use. MR uses genetic variants as instrumental variables to estimate the causal effect of an exposure on an outcome, if the assumptions are satisfied. DESIGN: Our primary method was inverse-variance weighted (IVW) regression and the robustness of these findings was assessed with five different sensitivity methods. SETTING: European ancestry. PARTICIPANTS: Summary-level data were drawn from the largest available independent genome-wide association studies (GWAS) of loneliness (n = 511 280), smoking (initiation (n = 249 171), cigarettes per day (n = 249 171) and cessation (n = 143 852), alcoholic drinks per week (n = 226 223) and alcohol dependence (n = 46 568). MEASUREMENTS: Genetic variants predictive of the exposure variable were selected as instruments from the respective GWAS. FINDINGS: There was weak evidence of increased loneliness leading to higher likelihood of initiating smoking, smoking more cigarettes, and a lower likelihood of quitting smoking. Additionally, there was evidence that initiating smoking increases loneliness [IVW, ß = 0.30, 95% confidence interval (CI) = 0.22-0.38, P = 2.8 × 10-13 ]. We found no clear evidence for a causal effect of loneliness on drinks per week (IVW, ß = 0.01, 95% CI = -0.11, 0.13, P = 0.865) or alcohol dependence (IVW, ß = 0.09, 95% CI = -0.19, 0.36, P = 0.533) nor of alcohol use on loneliness (drinks per week IVW, ß = 0.09, 95% CI = -0.02, 0.22, P = 0.076; alcohol dependence IVW, ß = 0.06, 95% CI = -0.02, 0.13, P  =  0.162). CONCLUSIONS: There appears to be tentative evidence for causal, bidirectional, increasing effects between loneliness and cigarette smoking, especially for smoking initiation increasing loneliness.

Distance to white matter trajectories is associated with treatment response to internal capsule deep brain stimulation in treatment-refractory depression.

BACKGROUND: Deep brain stimulation (DBS) is an innovative treatment for treatment-refractory depression. DBS is usually targeted at specific anatomical landmarks, with patients responding to DBS in approximately 50% of cases. Attention has recently shifted to white matter tracts to explain DBS response, with initial open-label trials targeting white matter tracts yielding much higher response rates (>70%). OBJECTIVE/HYPOTHESIS: Our aim was to associate distance to individual white matter tracts around the stimulation target in the ventral anterior limb of the internal capsule to treatment response. METHODS: We performed diffusion magnetic resonance tractography of the superolateral branch of the medial forebrain bundle and the anterior thalamic radiation in fourteen patients that participated in our randomized clinical trial. We combined the tract reconstructions with the postoperative images to identify the DBS leads and estimated the distance between tracts and leads, which we subsequently associated with treatment response. RESULTS: Stimulation closer to both tracts was significantly correlated to a larger symptom decrease (r = 0.61, p = 0.02), suggesting that stimulation more proximal to the tracts was beneficial. Biophysical modelling indicated that 37.5% of tracts were even outside the volume of activated tissue. There was no difference in lead placement with respect to anatomical landmarks, which could mean that differences in treatment response were driven by individual differences in white matter anatomy. CONCLUSIONS: Our results suggest that deep brain stimulation of the ventral anterior limb of the internal capsule could benefit from targeting white matter bundles. We recommend acquiring diffusion magnetic resonance data for each individual patient.

Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) reduces depressive symptoms in approximately 40%-60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period. METHODS: Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase. RESULTS: Of 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt. CONCLUSIONS: vALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD. TRIAL REGISTRATION NUMBER: NTR2118.

Misophonia is associated with altered brain activity in the auditory cortex and salience network.

Misophonia is characterized by intense rage and disgust provoked by hearing specific human sounds resulting in social isolation due to avoidance. We exposed patients with symptom provoking audiovisual stimuli to investigate brain activity of emotional responses. 21 patients with misophonia and 23 matched healthy controls were recruited at the psychiatry department of the Amsterdam UMC. Participants were presented with three different conditions, misophonia related cues (video clips with e.g. lip smacking and loud breathing), aversive cues (violent or disgusting clips from movies), and neutral cues (video clips of e.g. someone meditating) during fMRI. Electrocardiography was recorded to determine physiological changes and self-report measures were used to assess emotional changes. Misophonic cues elicited anger, disgust and sadness in patients compared to controls. Emotional changes were associated with increases in heart rate. The neuroimaging data revealed increased activation of the right insula, right anterior cingulate cortex and right superior temporal cortex during viewing of the misophonic video clips compared to neutral clips. Our results demonstrate that audiovisual stimuli trigger anger and physiological arousal in patients with misophonia, associated with activation of the auditory cortex and salience network.

Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use.

BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N = 25,508) and "tobacco use disorder" (N = 27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p = 2.39 × 10-7) and rs8034191 (p = 6.31 × 10-7) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.

Body Weight Changes after Deep Brain Stimulation for Obsessive-Compulsive Disorder or Depression.

BACKGROUND: In 2010, we published an often-cited case report describing smoking cessation and substantial weight loss after deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) in an obese patient. To test whether this single observation was also observed in the treated population at large, the weight changes of a larger cohort of patients who underwent DBS for OCD or major depressive disorder (MDD) were studied. RESULTS: Data were available for 46 patients (30 OCD and 16 MDD patients; mean age 46.2 years, SD 10.9) with an average baseline body mass index (BMI) of 28.0 (SD 7.3), 26 of whom (57%) were overweight (n = 11), obese (n = 12), or morbidly obese (n = 3). Mean follow-up was 3.8 years (range 10 months to 8.7 years, SD 2.3), after which the average BMI was 28.1 (SD 7.0), not significantly different from baseline. The average BMI of the 15 patients with (morbid) obesity at baseline decreased from 36.8 to 34.6 (ns), while the average BMI of the 31 normal or "only" overweight patients at baseline increased from 23.8 to 25.0 (ns). CONCLUSION: There was no significant change in body weight on group level after DBS for either OCD or MDD.

Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on autobiographical memories has never been established. OBJECTIVE: Comparing autobiographical memories following DBS and ECT. METHODS: In two hospitals in The Netherlands, we interviewed 25 TRD patients treated with DBS of the ventral anterior limb of the internal capsule (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective, longitudinal study between March 2010 and August 2016. Patients treated with DBS were interviewed before surgery, after surgery, and twice during treatment over 122.7 (SD: ±22.2) weeks. Patients treated with ECT were tested before ECT, after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1 (±9.3) weeks. Controls were tested four times over 81.5 (±15.6) weeks. RESULTS: Compared to HC, the AMI-SF score decreased faster in both TRD groups (P < 0.001). More specifically, AMI-SF score decreased in a comparable rate as HC after DBS surgery, but decreased more during treatment. The AMI-SF decrease in the ECT group was larger than both the DBS and HC groups. CONCLUSIONS: Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline.

Elective amputation of a "healthy limb".

Patients with body integrity identity disorder (BIID) experience a strong desire for amputation from very early on. BIID patients are often dismissed when they share their wish for amputation with surgeons. Consequently, patients resort to self-amputation, including complications and sometimes death. BIID patients are not psychotic and are mentally competent to oversee the consequences of an elective amputation. The authors offer arguments in favor of elective amputation.

Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial.

IMPORTANCE: Patients with treatment-resistant depression (TRD) do not respond sufficiently to several consecutive treatments for major depressive disorder. Deep brain stimulation (DBS) is a promising treatment for these patients, but presently placebo effects cannot be ruled out. OBJECTIVE: To assess the efficacy of DBS of the ventral anterior limb of the internal capsule (vALIC), controlling for placebo effects with active and sham stimulation phases. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five patients with TRD from 2 hospitals in the Netherlands were enrolled between March 22, 2010, and May 8, 2014. Patients first entered a 52-week open-label trial during which they received bilateral implants of 4 contact electrodes followed by optimization of DBS until a stable response was achieved. A randomized, double-blind, 12-week crossover phase was then conducted with patients receiving active treatment followed by sham or vice versa. Response and nonresponse to treatment were determined using intention-to-treat analyses. INTERVENTIONS: Deep brain stimulation targeted to the vALIC. MAIN OUTCOMES AND MEASURES: The change in the investigator-rated score of the 17-item Hamilton Depression Rating Scale (HAM-D-17) was the main outcome used in analysis of the optimization phase. The primary outcome of the crossover phase was the difference in the HAM-D-17 scores between active and sham DBS. The score range of this tool is 0 to 52, with higher scores representing more severe symptoms. Patients were classified as responders to treatment (≥50% decrease of the HAM-D-17 score compared with baseline) and partial responders (≥25 but <50% decrease of the HAM-D-17 score). RESULTS: Of 25 patients included in the study, 8 (32%) were men; the mean (SD) age at inclusion was 53.2 (8.4) years. Mean HAM-D-17 scores decreased from 22.2 (95% CI, 20.3-24.1) at baseline to 15.9 (95% CI, 12.3-19.5) (P = .001), Montgomery-Åsberg Depression Rating Scale scores from 34.0 (95% CI, 31.8-36.3) to 23.8 (95% CI, 18.4-29.1) (P < .001), and Inventory of Depressive Symptomatology-Self-report scores from from 49.3 (95% CI, 45.4-53.2) to 38.8 (95% CI, 31.6-46.0) (P = .005) in the optimization phase. Following the optimization phase, which lasted 51.6 (22.0) weeks, 10 patients (40%) were classified as responders and 15 individuals (60%) as nonresponders. Sixteen patients entered the randomized crossover phase (9 responders [56%], 7 nonresponders [44%]). During active DBS, patients scored significantly lower on the HAM-D-17 scale (13.6 [95% CI, 9.8-17.4]) than during sham DBS (23.1 [95% CI, 20.6-25.6]) (P < .001). Serious adverse events included severe nausea during surgery (1 patient), suicide attempt (4 patients), and suicidal ideation (2 patients). CONCLUSIONS AND RELEVANCE: Deep brain stimulation of the vALIC resulted in a significant decrease of depressive symptoms in 10 of 25 patients and was tolerated well. The randomized crossover design corroborates that vALIC DBS causes symptom reduction rather than sham. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2118.

Cigarette smoking in patients with obsessive compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS).

Obsessive compulsive disorder (OCD) showed a lower prevalence of cigarette smoking compared to other psychiatric disorders in previous and recent reports. We assessed the prevalence and clinical correlates of the phenomenon in an international sample of 504 OCD patients recruited through the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) network. Cigarette smoking showed a cross-sectional prevalence of 24.4% in the sample, with significant differences across countries. Females were more represented among smoking patients (16% vs 7%; p<.001). Patients with comorbid Tourette's syndrome (p<.05) and tic disorder (p<.05) were also more represented among smoking subjects. Former smokers reported a higher number of suicide attempts (p<.05). We found a lower cross-sectional prevalence of smoking among OCD patients compared to findings from previous studies in patients with other psychiatric disorders but higher compared to previous and more recent OCD studies. Geographic differences were found and smoking was more common in females and comorbid Tourette's syndrome/tic disorder.