Disrupting disordered neurocircuitry : treating refractory psychiatric illness with neuromodulation

Despite the premature and somewhat infamous rise and fall of psychosurgery in the mid-20th century, the current era of functional neuromodulation proffers immense opportunity for surgical intervention in treatment-resistant psychiatric disorders. On the basis of recent successes with novel, focused, less invasive, and reversible treatment strategies for movement disorders, several therapeutic trials have been conducted to investigate the effectiveness of deep brain stimulation (DBS) in treatment-resistant depression, obsessive-compulsive disorder (OCD), and Tourette syndrome. The many anatomic targets for these psychiatric disorders are indicative of both the system-wide effects of DBS and the network-level dysfunction mediating the emotional and cognitive disturbances. To gain insight into the application of neuromodulation therapies and their further advancement, we must elucidate neuroanatomic networks involved in refractory psychiatric illness, the neurophysiological anomalies that contribute to disordered information processing therein, and the local and system-wide modulatory effects of DBS. This review discusses the history of psychosurgical procedures, recent DBS clinical data, current anatomic models of psychopathology, and possible therapeutic mechanisms of action of DBS neuromodulation. Our search criteria for PubMed included combinations of the following terms: neuromodulation, DBS, depression, OCD, Tourette syndrome, mechanism of action, and history. Dates were not restricted. As clinical and basic scientific investigations probe the neuromodulatory effects of DBS in the treatment of refractory neuropsychiatric illness, our knowledge of these disorders and our potential to treat them are rapidly expanding. Indeed, this modern era of neuromodulation may provide the key that unlocks many of the mysteries pertaining to the biological basis of disordered emotional neurocircuitry.

Cigarette smoking, nicotine dependence and anxiety disorders : a systematic review of population-based, epidemiological studies

Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized.

Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders.

Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified.

Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of panic disorder and generalized anxiety disorder. The literature assessing anxiety disorders increasing smoking and nicotine dependence is inconsistent. Potential issues with the current literature are discussed and directions for future research are suggested.

Anxiety online - a virtual clinic : preliminary outcomes following completion of five fully automated treatment programs for anxiety disorders and symptoms

Background : The development of e-mental health interventions to treat or prevent mental illness and to enhance wellbeing has risen rapidly over the past decade. This development assists the public in sidestepping some of the obstacles that are often encountered when trying to access traditional face-to-face mental health care services. Objective : The objective of our study was to investigate the posttreatment effectiveness of five fully automated self-help cognitive behavior e-therapy programs for generalized anxiety disorder (GAD), panic disorder with or without agoraphobia (PD/A), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD) offered to the international public via Anxiety Online, an open-access full-service virtual psychology clinic for anxiety disorders. Methods : We used a naturalistic participant choice, quasi-experimental design to evaluate each of the five Anxiety Online fully automated self-help e-therapy programs. Participants were required to have at least subclinical levels of one of the anxiety disorders to be offered the associated disorder-specific fully automated self-help e-therapy program. These programs are offered free of charge via Anxiety Online. Results : A total of 225 people self-selected one of the five e-therapy programs (GAD, n = 88; SAD, n = 50; PD/A, n = 40; PTSD, n = 30; OCD, n = 17) and completed their 12-week posttreatment assessment. Significant improvements were found on 21/25 measures across the five fully automated self-help programs. At postassessment we observed significant reductions on all five anxiety disorder clinical disorder severity ratings (Cohen d range 0.72–1.22), increased confidence in managing one’s own mental health care (Cohen d range 0.70–1.17), and decreases in the total number of clinical diagnoses (except for the PD/A program, where a positive trend was found) (Cohen d range 0.45–1.08). In addition, we found significant improvements in quality of life for the GAD, OCD, PTSD, and SAD e-therapy programs (Cohen d range 0.11–0.96) and significant reductions relating to general psychological distress levels for the GAD, PD/A, and PTSD e-therapy programs (Cohen d range 0.23–1.16). Overall, treatment satisfaction was good across all five e-therapy programs, and posttreatment assessment completers reported using their e-therapy program an average of 395.60 (SD 272.2) minutes over the 12-week treatment period. Conclusions : Overall, all five fully automated self-help e-therapy programs appear to be delivering promising high-quality outcomes; however, the results require replication.

The relationship between body dysmorphic disorder symptoms and self-construals

Background:  Cognitive models of body dysmorphic disorder (BDD) suggest that beliefs and evaluations related to self-concept are central to the maintenance of the disorder, but such beliefs have received little empirical attention. This study examined the relative importance of contingent self-worth and self-ambivalence to BDD symptoms in comparison to their importance to obsessive–compulsive disorder and social phobia symptoms.

Method:  The sample comprised 194 non-clinical participants (female, N = 148; males, N = 46) with a mean age of 24.70 years (standard deviation = 9.34). Participants were asked to complete a battery of self-report questionnaires. Results:  While significant relationships were found between the self-beliefs and symptoms of all three disorders, some specificity was found in the relationships.

Conclusions:  Self-worth based upon appearance was most important in BDD, while contingent self-worth based on the approval of others was important in social phobia. Self-ambivalence was associated with each disorder. Implications and limitations are discussed.

The influence of confidence in memory on checking behaviours

Recent theories of Obsessive Compulsive Disorder have suggested that meta-cognitive beliefs, particular confidence in memory, may relate to the maintenance of symptoms. For example, individuals who worry that their memory is deficient may check in order to ensure that the doors are locked, regardless of their actual memory ability. While studies have related meta-memory beliefs to OCD symptoms, and have found that memory is affected by checking behaviours; to date, no experimental literature has attempted to ascertain whether lowered confidence in memory directly leads to greater checking behaviours. In the current study 46 non-clinical participants completed a battery of questionnaires measuring these constructs, before undertaking a “memory task” designed to manipulate their level of confidence in their memory. The effect of the manipulation on the level of checking on a visuomemory task was subsequently assessed. The questionnaires indicated that cognitive confidence predicted variation in obsessive-compulsive symptoms over-and-above the influence of depressive symptoms and other OCD-related beliefs. However, while confidence in memory was successfully manipulated, the group with increased memory confidence was not found to have lower checking behaviours. Limitations of the study are discussed and directions for further research are suggested.

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.

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.