Autoantibodies in patients with obsessive-compulsive disorder: a systematic review.

Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are high. Emerging evidence suggests that biological components, especially autoimmune processes, may be associated with some cases of OCD and treatment resistance. Therefore, this systematic literature review summarizing all case reports/case series as well as uncontrolled and controlled cross-sectional studies investigating autoantibodies in patients with OCD and obsessive-compulsive symptoms (OCS) was performed. The following search strategy was used to search PubMed: "(OCD OR obsessive-compulsive OR obsessive OR compulsive) AND (antib* OR autoantib* OR auto-antib* OR immunoglob* OR IgG OR IgM OR IgA)". Nine case reports with autoantibody-associated OCD/OCS were identified: five patients with anti-neuronal autoantibodies (against N-methyl-D-aspartate-receptor [NMDA-R], collapsin response mediator protein [CV2], paraneoplastic antigen Ma2 [Ma2], voltage gated potassium channel complex [VGKC], and "anti-brain" structures) and four with autoantibodies associated with systemic autoimmune diseases (two with Sjögren syndrome, one with neuropsychiatric lupus, and one with anti-phospholipid autoantibodies). Six patients (67%) benefited from immunotherapy. In addition, eleven cross-sectional studies (six with healthy controls, three with neurological/psychiatric patient controls, and two uncontrolled) were identified with inconsistent results, but in six studies an association between autoantibodies and OCD was suggested. In summary, the available case reports suggest an association between OCD and autoantibodies in rare cases, which has been supported by initial cross-sectional studies. However, scientific data is still very limited. Thus, further studies on autoantibodies investigated in patients with OCD compared with healthy controls are needed.

Immunological causes of obsessive-compulsive disorder: is it time for the concept of an "autoimmune OCD" subtype?

Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of "autoimmune OCD" is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for "autoimmune OCD" could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.

Testing an emotion regulation model of physical activity in adolescents with anorexia nervosa: A pilot ecological momentary assessment.

OBJECTIVE: Adolescents with anorexia nervosa (AN) often show increased levels of exercise and physical activity. Psychological models suggest that physical activity in AN might attenuate momentary negative affect. However, this has not been directly tested in adolescents with AN, and it remains unclear whether this is a distinct mechanism of physical activity in AN compared with healthy controls (HCs). METHOD: In a 1-day ecological momentary assessment, 32 adolescent inpatients with AN and 30 HCs responded to hourly questions on momentary affect while wearing an actigraph to objectively assess physical activity. RESULTS: Linear mixed models identified that adolescents with AN experienced more aversive tension, more negative affect, and less positive affect throughout the day than HCs. Preliminary evidence for a momentary association of higher levels of physical activity with positive affect were found for both groups, whereas higher levels of physical activity were associated with less negative affect in adolescents with AN only. When correcting for multiple testing, interactions did not hold statistical significance. DISCUSSION: Our results indicate a down-regulation effect of physical activity on negative affect for AN and a more general up-regulation effect of positive affect. However, our sample size was small, and replication of our findings is needed.

The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

['Optimal care for depression': Freiburg model of integrated care for depressive disorders]. / "Optimal versorgt bei Depression" - Freiburger Modell zur Integrierten Versorgung depressiver Erkrankungen.

BACKGROUND: Health care for persons with depressive disorders is not networked to an optimal degree in Germany. In order to improve outpatient care, an integrated care model for patients with depressive disorders was initiated in Freiburg in December 2008. The model aims at implementation of central recommendations of the "Conceptual Framework Integrated Care: Depression" of the German Association for Psychiatry and Psychotherapy. METHODS: Usage of health services and effects of the model were analyzed by means of patient and physician data as part of a continuous project evaluation. RESULTS: Since the launch of the project in December 2008, 40 physicians have been participating, and have included a total of 234 patients. Unipolar depressions constitute by far the most frequent disorders (91%). Most patients showed moderate (58%) or severe (36%) depressive symptoms. Most disorders were recurrent (61%). About three quarters of patients (75%) are treated exclusively by general practitioners. According to the physicians' ratings, 58% of the patients were remitted or showed subsyndromal symptoms in the eighth treatment week following their inclusion in the Freiburg model. After 16 weeks this number rose to 70% of patients. According to the information provided by the patients, in the PHQ-D, 59% of the patients were remitted or showed minimal symptoms. CONCLUSIONS: In the Freiburg model the "Conceptual Framework Integrated Care: Depression" could be implemented under current routine conditions. The first evaluation results indicate the success of this model. The results are indicative of a high quality of health care of the Freiburg model.

Periodic leg movements in sleep and periodic limb movement disorder: prevalence, clinical significance and treatment.

Periodic leg movements in sleep (PLMS) are a frequent finding in polysomnography. The prevalence of PLMS is estimated to be 4-11% in adults. In childhood, PLMS rarely occur although medical conditions like sleep apnea syndrome or neuropsychiatric disorders can lead to high rates of PLMS. In the elderly, PLMS are also common in subjects without sleep disturbances. In sleep studies, PLMS are found most frequently in restless legs syndrome (RLS) and often occur in narcolepsy, sleep apnea syndrome and REM sleep behavior disorder. Some patients with otherwise unexplained insomnia or hypersomnia reveal an elevated number of PLMS, a condition defined as periodic limb movement disorder (PLMD). PLMS were found also in various medical and neurological disorders that do not primarily affect sleep. A summary of these is presented. In sleep disorders related to dopaminergic dysfunction such as RLS, PLMS are considered to be a symptom of the disease. In other disorders like primary insomnia, the clinical relevance of PLMS is still being controversially discussed. Studies with findings both pro and contra are referred. To date, only a few studies have evaluated the efficacy of therapeutic substances in reducing PLMS in PLMD patients. Their results need to be confirmed in controlled randomized trials.

Increased nocturnal interleukin-6 excretion in patients with primary insomnia: a pilot study.

The aim of the present study was to investigate whether there is a difference in evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary insomnia compared to controls. We hypothesized that in insomniac patients, the excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations in 11 patients (two males and nine females) with primary insomnia and 11 age and gender-matched healthy controls. Sleep was monitored polysomnographically for three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2-h intervals were performed prior to and during the last laboratory night. Polysomnographically determined sleep parameters and subjective ratings of sleep demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL-6 secretion was significantly increased (p<.05) in insomniac patients for the whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x 2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion correlated inversely with subjectively perceived sleep quality and amount of slow wave sleep in the insomniac patients. Amount of Wake Time correlated positively with IL-6 excretion in insomniacs. The results of the present study demonstrate significantly increased nocturnal IL-6 secretion in insomniacs. It might be speculated that chronic primary insomnia with polysomnographically documented sleep impairments activates the production of IL-6 analogous to sleep deprivation studies in healthy subjects. This might also implicate a higher risk for inflammatory and cardiovascular diseases in patients with chronic insomnia.