Successful deep brain stimulation of the nucleus accumbens in severe alcohol dependence is associated with changed performance monitoring.

Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error-related negativity) linked to anterior mid-cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect on addiction trough a normalization of craving associated with aMCC dysfunction.

Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE: After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. METHOD: A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). RESULTS: Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. CONCLUSIONS: Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00159120.

Deep brain stimulation for psychiatric disorders.

BACKGROUND: Deep brain stimulation (DBS), an established treatment for some movement disorders, is now being used experimentally to treat psychiatric disorders as well. In a number of recently published case series, DBS yielded an impressive therapeutic benefit in patients with medically intractable psychiatric diseases. METHODS: This review of the use of DBS to treat psychiatric disorders is based on literature retrieved from a selective Pubmed search for relevant keywords, reference works on the topic, and the authors' own research. RESULTS: Studies have been performed on the use of DBS to treat medically intractable obsessive-compulsive disorder, depressive disorders, and Tourette syndrome. The case numbers in the cited publications were small, yet at least some of them involved a methodologically sound investigation. Thus, in some studies, the strength of the effect was controlled with a double-blinded interval in which the stimulation was turned off. In general, the primary symptoms were found to improve markedly, by 35% to 70%, although not all patients responded to the treatment. Adverse effects of DBS were very rare in most studies and could usually be reversed by changing the stimulation parameters. CONCLUSIONS: The results of DBS for psychiatric disorders that have been published to date are encouraging. They open up a new perspective in the treatment of otherwise intractable disorders. Nonetheless, the efficacy, mechanism of action, and adverse effects of DBS for this indication still need to be further studied in methodologically adequate trials that meet the highest ethical standard.

Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year.

OBJECTIVE: To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized. METHODS: The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function. RESULTS: The mean Y-BOCS scores decreased significantly from 32.2 (+/-4.0) at baseline to 25.4 (+/-6.7) after 12 months (p=0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated. CONCLUSIONS: DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.

Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders.

BACKGROUND: To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group. METHOD: PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score >61 (Global Assessment of Functioning Scale), SOFAS score >61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore >40 (Medical Outcomes Study-Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid clinical and sociodemographic predictors. RESULTS: In total, 52 patients (20%) fulfilled the criteria for functional remission, 125 patients (48%) achieved symptomatic resolution and when criteria for functional remission and symptomatic resolution were combined 33 patients (13%) achieved complete remission. Younger age, employment, a shorter duration of illness, a shorter length of current episode, less suicidality, and a lower PANSS negative and global subscore at admission were predictive of functional remission. The regression model showed a predictive value of more than 80%. CONCLUSIONS: A significant association was found between functional remission and symptomatic resolution, indicating reasonable validity of the proposed definition for functional outcome. The revealed predictors for functional treatment outcome emphasize the need for psychosocial and vocational rehabilitation in schizophrenic patients.

Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications?

Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient's comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.

Disappearance of self-aggressive behavior in a brain-injured patient after deep brain stimulation of the hypothalamus: technical case report.

OBJECTIVE: Self-mutilation is a severe symptom of diseases with varying etiologies. It can be observed in the context of mental retardation and after traumatic brain injury. Pharmacological treatment approaches often prove ineffective. CLINICAL PRESENTATION: We report the case of a 22-year-old woman with repetitive self-mutilating behavior in the mouth area after severe traumatic brain injury. RESULTS: Bilateral deep brain stimulation of the posterior hypothalamus was conducted and resulted in the complete elimination of self-mutilation during a 4-month observation period. CONCLUSION: This technical case report indicates that deep brain stimulation of the posterior hypothalamus could be a promising approach in the treatment of severe self-mutilating behavior.

Depression during an acute episode of schizophrenia or schizophreniform disorder and its impact on treatment response.

The aim of the present study was to examine the relevance of depressive symptoms during an acute schizophrenic episode for the prediction of treatment response. Two hundred inpatients who fulfilled DSM-IV criteria for schizophrenia or schizophreniform disorders were assessed at hospital admission and after 6 weeks of inpatient treatment using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale for Depression (HAM-D). Depressive symptoms showed positive correlations with both positive and negative symptoms at admission and after 6 weeks, and decreased during 6 weeks of treatment. Pronounced depressive symptoms (HAM-D score> or =16) were found in 28% of the sample at admission and in 9% after 6 weeks of treatment. Depressive symptoms at admission predicted a greater improvement of positive and negative symptoms over 6 weeks of treatment, but also more, rather than fewer remaining symptoms after 6 weeks. Both results, however, lost statistical significance when analyses were controlled for the influence of positive and negative symptoms at admission. Therefore, the hypothesis that depressive symptoms are predictive of a favorable treatment response was not supported by the present study.

Transient Manic-like Episode Following Bilateral Deep Brain Stimulation of the Nucleus Accumbens and the Internal Capsule in a Patient With Tourette Syndrome.

Objective. Deep brain stimulation (DBS) increasingly attracts attention as a potential treatment of mental disorders. Beside depression and obsessive-compulsive disorders, DBS has already been shown to be beneficial for Tourette syndrome (TS). Clinical Presentation/Method. The authors report on the outcome of a patient with treatment-resistant TS who underwent bilateral DBS of the nucleus accumbens and the internal capsule. Results. Within the 10-month follow-up, a substantial reduction of tics has been observed. Yet, as a side-effect of DBS, the patient developed a transient manic-like episode when primarily stimulated by the most proximally contact in the internal capsule. Conclusions. This case supports the hypothesis that DBS of the nucleus accumbens and the internal capsule represents an effective therapeutic alternative for otherwise treatment-resistant TS. Yet, future controlled studies are needed to determine optimal stimulation parameters and to reduce negative side-effects such as transient hypomanic episodes.

Dissociation between key processes of social cognition in autism: impaired mentalizing but intact sense of agency.

Deficits in social cognition and interaction, such as in mentalizing and imitation behavior, are hallmark features of autism spectrum disorders. Both imitation and mentalizing are at the core of the sense of agency, the awareness that we are the initiators of our own behavior. Little evidence exists regarding the sense of agency in autism. Thus, we compared high-functioning adults with autism to healthy control subjects using an action monitoring and attribution task. Subjects with autism did not show deficits in this task, yet they showed significant mentalizing deficits. Our findings indicate a dissociation between the sense of agency and ascription of mental states in autism. We propose that social-cognitive deficits in autism may arise on a higher level than that of action monitoring and awareness.

Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications?

Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient's comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.

Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders.

OBJECTIVE: The aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes. METHOD: A total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS). RESULTS: At admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms. CONCLUSION: The results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations.