Closed loop deep brain stimulation: an evolving technology

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Fluoxetine treatment of acral lick dermatitis in dogs: a placebo-controlled randomized double blind trial.

The aim of the study was to assess the efficacy and tolerability of fluoxetine treatment of acral lick dermatitis (ALD) in dogs and to investigate ALD as an animal model of obsessive-compulsive disorder (OCD). Sixty-three dogs with ALD were treated with fluoxetine 20 mg daily, or placebo, for 6 weeks. In the fluoxetine group, owners rated both appearance of the lesion (t = 10.2, df = 29, P < 0.0001) and licking behavior (t = 10.2, df = 29, P < 0.0001) as significantly improved by the end of the trial. Veterinarian-rated pre- and post-treatment photographs showed statistically significant improvement in the fluoxetine group (mean = 2.55). There were no significant changes in the placebo group as rated by owners and veterinarians. These results demonstrate the efficacy of fluoxetine in the treatment of ALD and lend further support to ALD as an animal model of OCD.

Part 1—you can run but you can’t hide: intrusive thoughts on six continents

 Most cognitive approaches for understanding and treating obsessive-compulsive disorder (OCD) rest on the assumption that nearly everyone experiences unwanted intrusive thoughts, images and impulses from time to time. These theories argue that the intrusions themselves are not problematic, unless they are misinterpreted and/or attempts are made to control them in maladaptive and/or unrealistic ways. Early research has shown unwanted intrusions to be present in the overwhelming majority of participants assessed, although this work was limited in that it took place largely in the US, the UK and other 'westernised' or 'developed' locations. We employed the International Intrusive Thoughts Interview Schedule (IITIS) to assess the nature and prevalence of intrusions in nonclinical populations, and used it to assess (n=777) university students at 15 sites in 13 countries across 6 continents. Results demonstrated that nearly all participants (93.6%) reported experiencing at least one intrusion during the previous three months. Doubting intrusions were the most commonly reported category of intrusive thoughts; whereas, repugnant intrusions (e.g., sexual, blasphemous, etc.) were the least commonly reported by participants. These and other results are discussed in terms of an international perspective on understanding and treating OCD. © 2013 Elsevier Ltd.

Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review

N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.

Neurodevelopmental disorders

Attention-deficit/hyperactivity disorder (ADHD), depression, Tourette's syndrome (TS), obsessive-compulsive disorder (OCD), schizophrenia, and autism spectrum disorders (ASDs) are neurodevelopmental disorders thought to involve frontostriatal brain regions. This article outlines how each of these conditions is characterized in terms of gender ratios, prevalence rates, age of onset, and clinical presentation, as well as neuropsychological functioning and treatment. Also discussed are genetic factors and the different brain areas implicated from available neuroimaging data.

Prevalence of psychiatric co-morbidity in treatment-seeking problem gamblers: A systematic review and meta-analysis

OBJECTIVE: The aim of this paper was to systematically review and meta-analyse the prevalence of co-morbid psychiatric disorders (DSM-IV Axis I disorders) among treatment-seeking problem gamblers. METHODS: A systematic search was conducted for peer-reviewed studies that provided prevalence estimates of Axis I psychiatric disorders in individuals seeking psychological or pharmacological treatment for problem gambling (including pathological gambling). Meta-analytic techniques were performed to estimate the weighted mean effect size and heterogeneity across studies. RESULTS: Results from 36 studies identified high rates of co-morbid current (74.8%, 95% CI 36.5-93.9) and lifetime (75.5%, 95% CI 46.5-91.8) Axis I disorders. There were high rates of current mood disorders (23.1%, 95% CI 14.9-34.0), alcohol use disorders (21.2%, 95% CI 15.6-28.1), anxiety disorders (17.6%, 95% CI 10.8-27.3) and substance (non-alcohol) use disorders (7.0%, 95% CI 1.7-24.9). Specifically, the highest mean prevalence of current psychiatric disorders was for nicotine dependence (56.4%, 95% CI 35.7-75.2) and major depressive disorder (29.9%, 95% CI 20.5-41.3), with smaller estimates for alcohol abuse (18.2%, 95% CI 13.4-24.2), alcohol dependence (15.2%, 95% CI 10.2-22.0), social phobia (14.9%, 95% CI 2.0-59.8), generalised anxiety disorder (14.4%, 95% CI 3.9-40.8), panic disorder (13.7%, 95% CI 6.7-26.0), post-traumatic stress disorder (12.3%, 95% CI 3.4-35.7), cannabis use disorder (11.5%, 95% CI 4.8-25.0), attention-deficit hyperactivity disorder (9.3%, 95% CI 4.1-19.6), adjustment disorder (9.2%, 95% CI 4.8-17.2), bipolar disorder (8.8%, 95% CI 4.4-17.1) and obsessive-compulsive disorder (8.2%, 95% CI 3.4-18.6). There were no consistent patterns according to gambling problem severity, type of treatment facility and study jurisdiction. Although these estimates were robust to the inclusion of studies with non-representative sampling biases, they should be interpreted with caution as they were highly variable across studies. CONCLUSIONS: The findings highlight the need for gambling treatment services to undertake routine screening and assessment of psychiatric co-morbidity and provide treatment approaches that adequately manage these co-morbid disorders. Further research is required to explore the reasons for the variability observed in the prevalence estimates.

The role of fear of self and responsibility in obsessional doubt processes: a bayesian hierarchical model

The literature concerning obsessive-compulsive disorder (OCD) indicates that obsessions frequently imply negative evaluative beliefs regarding the self. The construct of the feared self has been used to describe the set of harmful attributes an individual worries they may possess. This study aimed to partially replicate previous research that demonstrated a relationship between feared-self beliefs and obsessional doubt in OCD-relevant contexts. The relationship between perceptions of personal responsibility and associated levels of doubt was also examined. Nonclinical participants (N = 221; 155 female; Mage = 26.4, SD = 9.2) were presented with vignettes related to checking and non OCD-relevant themes, which quantified doubt through the presentation of alternating reality-based (i.e., sensory) and possibility-based information. Of the total sample, 112 participants were randomly allocated to a personally relevant condition (in which the action implied in the vignettes was completed by the reader), and 109 were allocated to a second, other-relevant, condition (in which the action implied in the vignettes was completed by a proximal other). The results provided support for reasoning processes implicated in OCD, suggesting that feared-self beliefs may partially contribute to heightened levels of doubt in response to possibility vs. reality-based information in OCD-relevant contexts. Personal relevance contributed to greater baseline levels of doubt, but not to greater responses to the reality- and possibility-based statements accompanying the OCD-relevant vignette. Implications for theory and future research are discussed.

Examining the feasibility and tolerability of a clinically informed multisite, repetitive transcranial magnetic stimulation protocol

BACKGROUND: Multi-site repetitive transcranial magnetic stimulation (rTMS) has been applied experimentally in the treatment of obsessive compulsive disorder (OCD). NEW METHOD: This study was conducted to systematically evaluate the safety, tolerability and neurocognitive effects of rTMS applied to three cortical regions over a period of three months. NEW METHOD: Twenty healthy participants aged 22-33 years were randomly allocated to receive one session of active or sham stimulation of low and high frequency rTMS applied sequentially to the pre-supplementary motor area, right-dorsolateral prefrontal cortex and left-orbitofrontal cortex totalling 9min. Tolerability and safety was evaluated using a standardised safety questionnaire. Neurocognitive functioning was examined using the Cambridge Neuropsychological Test Automated Battery and measures of verbal fluency from the Delis-Kaplan Executive Functioning Test™ at five time points over three months. RESULTS: The protocol was safe and tolerable. Frequencies of minor adverse effects were higher in active (17 endorsements) than sham (1 endorsement) conditions. No between group differences in neurocognitive functioning were identified over three months. COMPARISON WITH EXISTING METHOD: This study is the first to evaluate the feasibility of low and high frequency parameters applied sequentially in a single session to the three selected cortical regions whilst providing neurocognitive data. CONCLUSIONS: rTMS applied sequentially over three cortical regions was found to be safe and tolerable in healthy individuals with no major neurocognitive effects over three months. Such findings can be used to inform the development of rTMS protocols involving multi-site stimulation for OCD.

The prevalence of comorbid personality disorders in treatment-seeking problem gamblers: a systematic review and meta-analysis

The aim of this study was to systematically review and meta-analyze the prevalence of comorbid personality disorders among treatment-seeking problem gamblers. Almost one half (47.9%) of problem gamblers displayed comorbid personality disorders. They were most likely to display Cluster B disorders (17.6%), with smaller proportions reporting Cluster C disorders (12.6%) and Cluster A disorders (6.1%). The most prevalent personality disorders were narcissistic (16.6%), antisocial (14.0%), avoidant (13.4%), obsessive-compulsive (13.4%), and borderline (13.1%) personality disorders. Sensitivity analyses suggested that these prevalence estimates were robust to the inclusion of clinical trials and self-selected samples. Although there was significant variability in reported rates, subgroup analyses revealed no significant differences in estimates of antisocial personality disorder according to problem gambling severity, measure of comorbidity employed, and study jurisdiction. The findings highlight the need for gambling treatment services to conduct routine screening and assessment of co-occurring personality disorders and to provide treatment approaches that adequately address these comorbid conditions.

The prevalence, age distribution and comorbidity of personality disorders in Australian women

OBJECTIVE: We aimed to describe the prevalence and age distribution of personality disorders and their comorbidity with other psychiatric disorders in an age-stratified sample of Australian women aged ⩾25 years. METHODS: Individual personality disorders (paranoid, schizoid, schizotypal, histrionic, narcissistic, borderline, antisocial, avoidant, dependent, obsessive-compulsive), lifetime mood, anxiety, eating and substance misuse disorders were diagnosed utilising validated semi-structured clinical interviews (Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition and Structured Clinical Interview for DSM-IV Axis II Personality Disorders). The prevalence of personality disorders and Clusters were determined from the study population (n = 768), and standardised to the Australian population using the 2011 Australian Bureau of Statistics census data. Prevalence by age and the association with mood, anxiety, eating and substance misuse disorders was also examined. RESULTS: The overall prevalence of personality disorders in women was 21.8% (95% confidence interval [CI]: 18.7, 24.9). Cluster C personality disorders (17.5%, 95% CI: 16.0, 18.9) were more common than Cluster A (5.3%, 95% CI: 3.5, 7.0) and Cluster B personality disorders (3.2%, 95% CI: 1.8, 4.6). Of the individual personality disorders, obsessive-compulsive (10.3%, 95% CI: 8.0, 12.6), avoidant (9.3%, 95% CI: 7.1, 11.5), paranoid (3.9%, 95% CI: 3.1, 4.7) and borderline (2.7%, 95% CI: 1.4, 4.0) were among the most prevalent. The prevalence of other personality disorders was low (⩽1.7%). Being younger (25-34 years) was predictive of having any personality disorder (odds ratio: 2.36, 95% CI: 1.18, 4.74), as was being middle-aged (odds ratio: 2.41, 95% CI: 1.23, 4.72). Among the strongest predictors of having any personality disorder was having a lifetime history of psychiatric disorders (odds ratio: 4.29, 95% CI: 2.90, 6.33). Mood and anxiety disorders were the most common comorbid lifetime psychiatric disorders. CONCLUSIONS: Approximately one in five women was identified with a personality disorder, emphasising that personality disorders are relatively common in the population. A more thorough understanding of the distribution of personality disorders and psychiatric comorbidity in the general population is crucial to assist allocation of health care resources to individuals living with these disorders.

N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial

Nail biting is a common behavioral problem. While there are established behavioral interventions for management, they are of modest efficacy, and there is minimal evidence for effective pharmacotherapy. This study investigated the role of N-acetylcysteine (NAC) a potent glutathione and glutamate modulator for the treatment of pathological nail biting in children and adolescents. This pilot randomized, double-blind, placebo-controlled clinical trial of NAC (800mg/day) or placebo enrolled 42 children and adolescents with chronic nail biting. Nail length was the objective outcome. Evaluations were carried out three times; before treatment, one month after enrollment in the study, and two months after enrollment. The duration (chronicity) of nail biting in the NAC and placebo groups was 3.63(2.45) and 5.09(3.74) years (P=0.14). The mean nail length gradually increased in both the NAC and placebo groups during this trial. There was a statistically significant difference between the two groups regarding increased nail length after the first month of trial [(5.21(5.75) and 1.18(3.02) millimeters], however no difference after two months was observed. Two patients in the NAC group discontinued medication due to adverse events. One patient experienced headache, agitation, and social withdrawal, and another patient expressed severe aggression after taking medication and was withdrawn from the study. This study supports the hypothesis that NAC decreases nail biting behavior in children and adolescents over the short term. NAC is relatively well tolerated and severe adverse effects are rare. However, there was a high rate of dropout. Further studies with longer durations that build on these preliminary data are recommended.

An empirical investigation of hypersexuality

The aim of this study was to investigate the nature of hypersexuality and the personality factors associated with the desire for and experience of high frequency sexual behavior. Participants in the study were 69 male and 93 female university students. Respondents reported on their desire for and experience of masturbation, oral sex, sexual intercourse, pornography, indecent phone calls or letters, prostitution, exhibitionism, voyeurism, as well as providing self-report measures which evaluated their levels of state and trait anxiety, depression, obsessive and compulsive symptoms and fear of intimacy. The results demonstrated that subjects who engaged in high-frequency voyeurism were more depressed than low-frequency voyeurs. Respondents in the high-frequency sexual deviant desire and behavior groups appeared to have more obsessive-compulsive symptoms in comparison to the low-frequency deviant sexual behavior and desire groups. Increased psychopathology was not associated with high-frequency non-deviant sexual behaviors and desires. This finding raised the question of whether labels such as sexual compulsion and addiction are merely pathologizing illegal sexual behavior.