A Lack of Clinical Effect of High-frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised, Double-blind Trial.

Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high-frequency rTMS programme targeting the left DLPFC. Forty-seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55-second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high-frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Neural correlates of clinical improvement after deep transcranial magnetic stimulation (DTMS) for treatment-resistant depression: a case report using functional magnetic resonance imaging.

We report the effects of a 4-week trial of deep transcranial magnetic stimulation (DTMS) on depressive and anxious symptoms and brain activity in a patient (Mrs A) with treatment-resistant depression (TRD). The protocol involved a pre- and a post-functional magnetic resonance imaging (fMRI) scan during which Mrs A had to perform a working memory task (i.e., n-back). Her baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D21) was 24, indicating severe depressive symptoms. Immediately after 4 weeks of daily DTMS treatment applied over the left dorsolateral prefrontal cortex (DLPFC), her HAM-D21 score decreased to 13 (a 46% reduction), and 1 month later, it was 12 (a 50% reduction). Moreover, Mrs A's accuracy scores on the n-back task (i.e., 2-back condition) improved from 79% (baseline) to 96% (after DTMS treatment). At the neural level, Mrs A showed significantly increased brain activity in the working memory network (e.g., DLPFC, parietal cortex) during the execution of the 2-back condition after DTMS treatment compared to baseline.

Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression (MD). However, the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials. Thus, we conducted a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials (RCTs) on high frequency (HF-), low frequency (LF-) and bilateral rTMS for MD. We searched the literature from January 1995 to July 2012 using Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and Scopus. The main outcome measure was participants' ability to correctly guess their treatment allocation at study end. We used a random-effects model and risk difference (RD). Overall, data were obtained from seven and two RCTs on HF- and bilateral rTMS, respectively. No RCT on LF-rTMS reporting on blinding success was found. HF- and bilateral rTMS trials enrolled 396 and 93 depressed subjects and offered an average of approximately 13 sessions. At study end, 52 and 59% of subjects receiving HF-rTMS and sham rTMS were able to correctly guess their treatment allocation, a non-significant difference (RD = -0.04; z = -0.51; p = 0.61). Furthermore, 63.3 and 57.5% of subjects receiving bilateral and sham rTMS were able to correctly guess their treatment allocation, also a non-significant difference (RD = 0.05; z = 0.49; p = 0.62). In addition, the use of angulation and sham coil in HF-rTMS trials produced similar results. In summary, existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation.

Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials.

Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta-analysis to examine this issue. We searched the literature for randomized trials on head-to-head comparisons between HF-rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre-post changes in depression ratings, as well as overall dropout rates at study end. We used a random-effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges' g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF-rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges' g = -0.93; p = 0.007). No differences on dropout rates for HF-rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF-rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow-ups and more intense stimulation protocols are warranted.

Brain responses to body image stimuli but not food are altered in women with bulimia nervosa.

BACKGROUND: Research into the neural correlates of bulimia nervosa (BN) psychopathology remains limited. METHODS: In this functional magnetic resonance imaging study, 21 BN patients and 23 healthy controls (HCs) completed two paradigms: (1) processing of visual food stimuli and (2) comparing their own appearance with that of slim women. Participants also rated food craving and anxiety levels. RESULTS: Brain activation patterns in response to food cues did not differ between women with and without BN. However, when evaluating themselves against images of slim women, BN patients engaged the insula more and the fusiform gyrus less, compared to HCs, suggesting increased self-focus among women with BN whilst comparing themselves to a 'slim ideal'. In these BN patients, exposure to food and body image stimuli increased self-reported levels of anxiety, but not craving. CONCLUSIONS: Our findings suggest that women with BN differ from HCs in the way they process body image, but not in the way they process food stimuli.

Theory of mind in bulimia nervosa.

OBJECTIVE: This study aimed to investigate theory of mind (ToM) in individuals with bulimia nervosa (BN), an area neglected by empirical research despite social functioning difficulties in this disorder and evidence of ToM deficits in people with anorexia nervosa (AN). METHOD: ToM was assessed in 48 BN and 34 Eating Disorder Not Otherwise Specified BN-type (EDNOS-BN) outpatients and 57 healthy controls (HCs) using the Reading the Mind in the Eyes and the Reading the Mind in the Films (RMF), an ecologically valid task novel to BN research. RESULTS: Overall performance in BN and EDNOS-BN groups was equivalent to HCs on both tasks. Individuals with BN had enhanced negative emotion recognition on the RMF. DISCUSSION: Individuals with AN and BN have distinct socio-cognitive profiles. Further research into social cognition is required to establish the link between interpersonal difficulties and psychopathology in people with BN.

Validation of the social appearance anxiety scale in female eating disorder patients.

In the present study, we investigated the psychometric properties of the Social Appearance Anxiety Scale (SAAS) in a sample of 60 female eating disorder patients (M(age) = 27.82, SD = 9.76). The SAAS was developed to assess anxiety about being negatively evaluated for one's appearance. All patients completed the SAAS, the Eating Disorder Inventory-2, the Physical Health Questionnaire-9 Depression and the Dimensional Assessment of Personality Psychopathology. The SAAS demonstrated a one-factor structure and a high internal consistency. The SAAS was significantly positive in relation to body mass index, drive for thinness and body dissatisfaction. Concerning personality dimensions, the SAAS was positively related to emotional problems (e.g. depression, anxiety) and interpersonal problems (e.g. suspiciousness, submissiveness). Findings suggest that the SAAS is a psychometrically sound instrument to assess anxiety about being negatively evaluated about one's appearance in a sample of eating disorder patients.

Structural magnetic resonance imaging in eating disorders: a systematic review of voxel-based morphometry studies.

This systematic review summarises and critically appraises the literature on structural magnetic resonance imaging in people with a current or past eating disorder. Studies using voxel-based morphometry image analysis were included. Ten studies reported on a total of 236 people with a current or past eating disorder and 257 healthy controls. Sample heterogeneity prohibited a meta-analytic approach. The findings do not unequivocally indicate grey or white matter volume abnormalities in people with an eating disorder. Nevertheless, these preliminary data suggest that, compared with healthy controls, people with anorexia nervosa have decreased grey matter in a range of brain regions and that those with bulimia nervosa have increased grey matter volumes in frontal and ventral striatal areas. Research in the recovery phase and longitudinal studies suggest that potential brain tissue abnormalities may recover with clinical improvement. Overall, as the available data are inconclusive, further efforts in this field are warranted.

Risk factors, correlates, and markers in early-onset bulimia nervosa and EDNOS.

OBJECTIVE: This study aimed to investigate the specific risk factors, correlates, and markers associated with the development of symptomatology of early-onset BN and subclinical BN. METHOD: Two semi-structured interviews were used to examine symptomatology and antecedent factors of bulimic symptoms in a sample of British adolescents. RESULTS: Adolescents with early-onset eating pathology were significantly more likely to report an earlier age of menarche than those developing the disorder at the typical age, and were found to have a different pathway of symptom development. DISCUSSION: Increased awareness of this may help identify those particularly at risk for developing an early-onset of eating pathology.

Cotard's syndrome: a review.

Cotard's syndrome is a rare disorder in which nihilistic delusions concerning one's own body are the central feature. It is not listed as a specific disorder in the DSM-IV, as it is typically viewed as a part of other underlying disorders. However, it remains important to recognize the syndrome because specific underlying mechanisms are present, and prognostic and therapeutic consequences have to be taken into account. This review presents an up-to-date overview of Cotard's syndrome, which was initially described more than a century ago.

Quetiapine treatment and improved cognitive functioning in borderline personality disorder.

OBJECTIVE: We aimed to assess whether executive functioning improved over time in a sample of borderline personality disorder (BPD) subjects that took part in a quetiapine treatment trial. METHODS: Performance on the following neurocognitive tasks was assessed at enrolment and at the end of the 12 weeks quetiapine treatment: Trail Making Task, Word Fluency Task and Tower of London Task. Forty-one BPD patients were recruited, of whom 32 completed the trial. An intention-to-treat analysis with a mixed linear model was applied. RESULTS: The data show that participants significantly improved on most executive functioning measures. Patients' scores decreased significantly (mean [SD] difference; p-value) on the Trail Making Task Part A (11.7 [2.3]; p < 0.0001), Part B (51.8 [9.2]; p < 0.0001) and 'B minus A' (40.1 [8.2]; p < 0.0001), on a Phonological (15.9 [1.6]; p < 0.0001) and Semantic (9.8 [1.1]; p < 0.0001) Verbal Fluency tasks, and on the Tower of London total correct score (2.5 [0.4]; p < 0.0001), total move score (29.5 [4.5]; p < 0.0001) and total time (172.9 [35.8]; p < 0.0001). CONCLUSIONS: In this study we have demonstrated that executive functioning in BPD is improved after treatment with quetiapine. Neurocognitive measures of executive functioning should be considered as valuable outcomes in the study of treatment efficacy in BPD.

[Gilles de la Tourette syndrome mimicking an eating disorder]. / Yeme Bozuklugunu Taklit Eden Tourette Sendromu.

Vomiting and retching are behaviours that are part of the clinical manifestation of several disorders. Rarely, vomiting is actually tic and, when not recognized, may mislead physicians and other caregivers to erroneously diagnose a medical or psychiatric disorder without considering a tic-disorder. We report on an 18 year old male patient who demonstrated vomiting as main symptom. Initially, he was diagnosed with an eating disorder, bulimia nervosa purging type (DSM-IV TR). Firstly, he was not very able to suppress his vomiting, but later the vomiting became forced by putting fingers in his throat. This self-induced vomiting had a compulsive component and was performed after almost every meal. Psychiatric assessment disclosed a specific sequence of a premonitory epigastric feeling preceding the vomiting and relief after vomiting. History taking revealed that he had a childhood onset of motor tics (copropraxia which consisted of grabbing his genitalia, bilateral facial grimacing and sudden movements of the head) and phonic tics (sniffing and gargling). Furthermore, he had been treated with methylphenidate for a childhood diagnosis of Attention Deficit and Hyperactivity Disorder and suffered from obsessive-compulsive symptoms (OCS). His vomiting was considered a tic in the course of a Tourette syndrome. His score on the Yale Global Tic Severity Scale dropped from 74 at the first assessment to a score of 50 at week 4 of treatment with risperidone 0,5 mg/day and sertralin 25 mg/day. Sedation and sexual dysfunction occurred as adverse events. Vomiting as a tic is rare clinical manifestation, but this possibility should be considered when patients have a history of tics.

Euthanasia requests in a Canadian psychiatric emergency room: A case series: Part 1 of the McGill University euthanasia in psychiatry case series.

Euthanasia was decriminalized in Quebec in December 2015, and Canada-wide in June 2016. Both the Provincial and Federal legislation have limited the right to medical assistance in dying (MAID) to end-of-life cases; which makes MAID inaccessible to most patients solely suffering from psychiatric illness. While some end-stage anorexia nervosa or elderly patients may meet the end-of-life criterion because of their medical comorbidities or their age (Kelly et al., 2003), repeated suicide attempts or psychotic disorganization would not qualify since they would not be seen as elements of an illness leading to a foreseeable "natural death" (Canada, 2016). This is in contradiction to other jurisdictions, such as Belgium and the Netherlands as well as the eligibility criteria stated in the Supreme Court of Canada's decision in Carter v. Canada (Supreme Court of Canada, 2015). Here we analyze three cases of patients who presented to a psychiatric emergency department and requested MAID for psychiatric reasons. While none of the patients were eligible for MAID under Canadian law, we find that their demographics match closely that of patients granted MAID for psychiatric reasons in jurisdictions where that practice is allowed. Based on these cases, we comment on potentially negative consequences that may come from decriminalizing MAID for psychiatric reasons (such as an increased assessment burden on ED staff) and potentially positive consequences (such as encouraging suffering patients who had not consulted to seek care). While it is by no means our intention to take a political or moral stand on this important issue, or to conclusively weigh the negatives and positives of allowing MAID for psychiatric reasons, we do stress the importance of an active voice for psychiatry in this ongoing public debate.

High frequency repetitive transcranial magnetic stimulation treatment for major depression: Dissociated effects on psychopathology and neurocognition.

OBJECTIVES: This open-label pilot study explored the effects of a course of accelerated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on two neurocognitive domains (decision-making and impulse control) in patients with major depressive disorder (MDD). METHODS: Participants with MDD and a treatment resistant major depressive episode (n=24) underwent twice-daily HF-rTMS targeted at the left dorsolateral prefrontal cortex (lDLPFC) over two weeks. Psychopathology was assessed by clinician-administered and self-reported measures of depression and anxiety; decision-making was assessed by the Iowa Gambling Task, the Balloon Analog Risk Task and the Game of Dice Task; impulse control was assessed by the Stroop Color-Word Task, the Continuous Performance Task and the Stop-Signal Task. RESULTS: Depression and anxiety scores significantly improved from pre-post HF-rTMS treatment. However, none of the decision-making or impulse control variables of interest changed significantly from pre-post HF-rTMS. Moreover, there was no correlation between changes in psychopathological symptoms and in neurocognition. LIMITATIONS: This is a moderately sized open label trial, and the confounds of ongoing psychotropics and illness chronicity can not be excluded in this treatment resistant sample. CONCLUSIONS: There is dissociation between acute symptomatic benefit after a course of accelerated HF-rTMS applied to the lDLPFC in treatment resistant MDD and performance on tests of decision making and impulse control. Though rTMS appears cognitively safe, additional research is warranted to understand this potential dissociation and its putative clinical implications.

A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC). METHODS: In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms. OUTCOMES: The primary outcome measure was 'core AN symptoms', a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed. RESULTS: Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well-tolerated and was considered an acceptable intervention. CONCLUSIONS: This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy. TRIAL REGISTRATION: www.Controlled-Trials.com ISRCTN22851337.

Brain perfusion SPECT in impulsivity-related personality disorders.

BACKGROUND: Impulsive behaviours in patients with cluster B personality disorders are associated with low glucose metabolism and regional cerebral blood flow in the frontal cortex and subcortical structures. The aim of this study is to confirm the presence of a particular pattern of brain perfusion in a sample of borderline (BPD) and anti-social personality disorder (ASPD) patients using brain perfusion single photon emission computed tomography (SPECT). METHODS: A brain perfusion SPECT study was performed in 37 patients with BPD or ASPD (and no Axis I diagnosis) and 34 healthy control participants. Data were acquired on a triple head Toshiba gamma camera. Scatter and attenuation correction was done. Reconstructed SPECT images were analyzed by Statistical Parametrical Mapping (SPM99). RESULTS: There were no significant differences in age and gender distributions between the patients and the healthy controls. With regard to the functional imaging results, patients were characterized by a reduced regional cerebral blood flow (rCBF) in right temporal and prefrontal brain areas, including the right lateral temporal cortex (BA 21), the right frontopolar cortex (BA 10) and the right ventrolateral prefontal cortex (BA 47). CONCLUSIONS: Patients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Enhancing decision-making and cognitive impulse control with transcranial direct current stimulation (tDCS) applied over the orbitofrontal cortex (OFC): A randomized and sham-controlled exploratory study.

BACKGROUND: Decision-making and impulse control (both cognitive and motor) are complex interrelated processes which rely on a distributed neural network that includes multiple cortical and subcortical regions. Among them, the orbitofrontal cortex (OFC) seems to be particularly relevant as demonstrated by several neuropsychological and neuroimaging investigations. METHODS: In the present study we assessed whether transcranial direct current stimulation (tDCS) applied bilaterally over the OFC is able to modulate decision-making and cognitive impulse control. More specifically, 45 healthy subjects were randomized to receive a single 30-min session of active or sham anodal tDCS (1.5 mA) applied over either the left or the right OFC (coupled with contralateral cathodal tDCS). They were also assessed pre- and post-tDCS with a battery of computerized tasks. RESULTS: Our results show that participants who received active anodal tDCS (irrespective of laterality), vs. those who received sham tDCS, displayed more advantageous decision-making (i.e., increased Iowa Gambling Task "net scores" [p = 0.04]), as well as improved cognitive impulse control (i.e., decreased "interference" in the Stroop Word-Colour Task [p = 0.007]). However, we did not observe tDCS-related effects on mood (assessed by visual analogue scales), attentional levels (assessed by the Continuous Performance Task) or motor impulse control (assessed by the Stop-Signal Task). CONCLUSIONS: Our study potentially serves as a key translational step towards the development of novel non-invasive neuromodulation-based therapeutic interventions directly targeting vulnerability factors for psychiatric conditions such as suicidal behaviour and addiction.

Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: an open label trial.

BACKGROUND: Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4-6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. METHODS: In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6, and ≥ 50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. RESULTS: Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. LIMITATIONS: This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. CONCLUSION: An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials.

n-back task performance and corresponding brain-activation patterns in women with restrictive and bulimic eating-disorder variants: preliminary findings.

Eating disorder (ED) variants characterized by "binge-eating/purging" symptoms differ from "restricting-only" variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with "restricting-only" eating syndromes and 27 with "binge-eating/purging" variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with "binge-eating/purging" participants, "restricting-only" participants showed superior performance. Furthermore, in an intermediate-demand condition, "binge-eating/purging" participants showed significantly less event-related activation than did "restricting-only" participants in a right posterior prefrontal region spanning Brodmann areas 6-8-a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making.