Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Panic and fear induced by deep brain stimulation.

BACKGROUND: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region. OBJECTIVE: To investigate panic and fear resulting from DBS. METHODS: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions. RESULTS: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition CONCLUSIONS: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.

Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI.

The neurobiology relating to the insatiable appetite observed in Prader-Willi syndrome (PWS) has not been fully characterised. Two functional magnetic resonance imaging (fMRI) scans were performed on each of three adults with PWS. The scans were carried out pre- and post-treatment with the antiepileptic topiramate, which had little effect on body weight and appetite in these subjects. Subjects fasted overnight and drank a 75 g dextrose solution prior to fMRI scans for measurement of brain activation levels during/after glucose ingestion. Following glucose administration, there was a significant delay in activation at the hypothalamus and other brain regions associated with satiety compared with previous data on obese volunteers. These regions include the insula, ventromedial prefrontal cortex, and nucleus accumbens. Individuals with PWS showed a mean latency of 24 min while in a previous study obese volunteers had shown a latency of 15 min and lean volunteers a latency of 10 min in the hypothalamus. Our results provide evidence towards a satiety dysfunction in the central nervous system of PWS patients.

Disgust and the insula: fMRI responses to pictures of mutilation and contamination.

Although previous functional brain imaging studies have found that the insula responds selectively to facial expressions of disgust, it remains unclear whether the insula responds selectively to disgust-inducing pictures. In this fMRI study, healthy volunteers viewed pictures of contamination, human mutilation, attacks and neutral scenes during scanning, and then rated pictures for the 'basic' emotions. The anterior insula responded to contamination and mutilation but not attacks, while the ventral visual areas responded to attacks and mutilations more strongly than contamination. The above activations were predicted by disgust and arousal ratings respectively. Additionally, mutilations uniquely activated the right superior parietal cortex. These results support selective disgust processing at the insula, and suggest distinct neural responses to contamination and mutilation.

The psychobiology of obsessive-compulsive disorder: how important is the role of disgust?

Psychobiologic models of obsessive-compulsive disorder (OCD) have focused on cortico-striatal-thalamic-cortical (CTSC) circuits, noting normal function in cognitive and motoric procedural strategies. Such models have relied on the classification of OCD as an anxiety disorder, seldom exploring other relevant emotions. Based on the hypothesis that a central emotion in OCD is disgust, the authors review the literature on its psychobiology and its relevance to current models of OCD. There are important parallels between the psychobiology of OCD and that of disgust. Obsessive- compulsive disorder may be conceptualized in terms of a false contamination alarm in which disgust plays a crucial organizing or embodying role, not only at a basic brain level, but also in terms of the psychosocial aspects of the disorder. Just as psychobiologic models of panic disorder and post- traumatic stress disorder have been strengthened by the inclusion of preclinical work on amygdala-mediated fear conditioning, so findings on disgust and its mediating CSTC circuits may generate useful hypotheses for OCD research.

Treatment of binge-eating disorder with topiramate: a clinical case series.

BACKGROUND: Reduced appetite and weight loss were found in clinical trials of topiramate for epilepsy. Binge-eating disorder is characterized by recurrent episodes of binge eating that are not associated with regular use of inappropriate compensatory behaviors. Overweight and obesity may be common complications. To explore the effectiveness and tolerability of topiramate in binge-eating disorder, we describe the response of 13 consecutive outpatients with binge-eating disorder to naturalistic, open-label treatment with topiramate. METHOD: The response of 13 female outpatients with binge-eating disorder by DSM-IV criteria to naturalistic, open-label treatment with topiramate (100-1400 mg/day) was reviewed. Response of binge-eating disorder symptoms was clinically assessed as none, mild, moderate, marked, or remission. Weight and side effects were also evaluated. RESULTS: All 13 patients had comorbid Axis I psychiatric disorders along with binge-eating disorder and were receiving psychotropic medications at the time of topiramate administration. After beginning topiramate treatment, 9 patients displayed a moderate or better response of binge-eating disorder symptoms that was maintained for periods ranging from 3 to 30 months (mean +/- SD = 18.7+/-8.0 months). Two other patients displayed moderate or marked responses that subsequently diminished. The remaining 2 patients had a mild or no response. The mean +/- SD weight of the 13 patients decreased from 99.3+/-26.4 kg to 87.5+/-20.4 kg (z = -2.4, df = 1, p = .02), but only 7 patients lost > or = 5 kg of weight. The mean topiramate treatment dose was 492.3+/-467.8 mg/day for all 13 patients. The mean topiramate dose was higher in patients who lost > or = 5 kg than in patients who lost < 5 kg. Also, topiramate dose correlated significantly with weight loss (p < .01). In general, topiramate was well tolerated, with neurologic side effects the most common. Of 3 patients who discontinued topiramate because of side effects, 2 resumed the drug at a later date without significant recurrence of these effects. CONCLUSION: Topiramate may be an effective treatment for binge-eating disorder. Controlled studies of topiramate in binge-eating disorder appear warranted.

Psychiatric features of individuals with problematic internet use.

BACKGROUND: Problematic internet use has been described in the psychological literature as 'internet addiction' and 'pathological internet use'. However, there are no studies using face-to-face standardized psychiatric evaluations to identify behavioral characteristics, psychiatric comorbidity or family psychiatric history of individuals with this behavior. METHODS: Twenty individuals with problematic internet use were evaluated. Problematic internet use was defined as (1) uncontrollable, (2) markedly distressing, time-consuming or resulting in social, occupational or financial difficulties and (3) not solely present during hypomanic or manic symptoms. Evaluations included a semistructured interview about subjects' internet use, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID-IV), family psychiatric history and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) modified for internet use. RESULTS: All (100%) subjects' problematic internet use met DSM-IV criteria for an impulse control disorder (ICD) not otherwise specified (NOS). All 20 subjects had at least one lifetime DSM-IV Axis I diagnosis in addition to their problematic internet use (mean+/-SD=5.1+/-3.5 diagnoses); 14 (70.0%) had a lifetime diagnosis of bipolar disorder (with 12 having bipolar I disorder). LIMITATIONS: Methodological limitations of this study included its small sample size, evaluation of psychiatric diagnoses by unblinded investigators, and lack of a control group. CONCLUSIONS: Problematic internet use may be associated with subjective distress, functional impairment and Axis I psychiatric disorders.

Evaluation of bipolar disorder in inpatients with prelingual deafness.

OBJECTIVE: This study retrospectively examined the occurrence of bipolar disorder in patients with prelingual deafness who were hospitalized for a psychiatric disorder. METHOD: The hospital charts since 1983 of all psychiatrically admitted deaf patients were retrospectively evaluated for diagnoses by using DSM-IV criteria. Those with a best-estimate diagnosis of bipolar disorder were compared to those with other diagnoses. RESULTS: There were 28 patients with prelingual deafness who had at least one psychiatric diagnosis from 1983 to 1998. Upon chart review, 11 (39.3%) were diagnosed with bipolar disorder. Patients with bipolar disorder and deafness had rates of inaccurate discharge diagnoses that were similar to those of other deaf patients (70.8% versus 56.7%). CONCLUSIONS: Bipolar disorder may be more common in inpatients with prelingual deafness than has been previously described in the literature. Further research regarding the sources contributing to misdiagnosis of psychiatric disorders in this population is warranted.

Protein bound to mitochondrial DNA from tumor and normal tissues of humans and animals.

Stable mitochondrial (mt) DNA-protein complexes have been reported repeatedly in the last decade. We have found that the amount of proteins bound to mt DNA was increased in human HL-60 promyelocytic and chronic myelocytic leukemia cells. Mt of human tumor cells and bovine and rate liver cells were isolated by differential centrifugation. The DNA was purified by SDS-NaCl precipitation of protein, alcohol precipitation, and sucrose density gradient centrifugation. Mt DNA-bound protein obtained by enzymatic digestion of the DNA and purified by gel exclusion and reverse-phase HPLC chomatographies and SDS-polyacrylamide gel electrophoresis, showed a major protein band at 70 kD and a minor band at 35 kD. Hydrolysis of the mtDNA-protein complex in formic acid yielded DNA bases and peptides by HPLC on a C18 reverse-phase column. Tumor cell mtDNA contained 5-10 times more bound protein than mtDNA from normal tissue.