Marc-Andreas Edel

Increased risk of suicide under intrathecal ziconotide treatment? - A warning

Despite some other known psychiatric adverse effects, ziconotide is recommended for intrathecal pain treatment with a good efficacy and safety. Although some hints in previous studies are apparent, a higher suicidality has not been accepted as a treatment risk of ziconotide treatment by the investigators in the former randomized controlled trials so far. We present two cases supporting the suspicion of ziconotide-induced suicidality. Both showed no depressive symptoms at the time of treatment initiation. One patient performed suicide under low-dose (cumulative dosage: 779μg) 4 weeks after the onset of intrathecal ziconotide treatment despite sufficient pain relief. Another female patient with a history of depression, but free of symptoms under antidepressive medication since more than 15 years, developed severe suicidal ideation 2 months after ziconotide treatment (cumulative dosage: about 2900μg) with rapid recovery after drug discontinuation. The patient, who has completed suicide, had earlier given rise to discuss a potential depressive disorder, however, this diagnosis was scrapped, but the second patient had a clear history of depression. These cases substantiate the suspicion of a causal relationship between ziconotide and suicidality even in symptom-free patients with a history of depression. Therefore, a comprehensive psychiatric evaluation is unavoidable before and during ziconotide treatment.

Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.

Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntingtons disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntingtons disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntingtons disease.

Oxytocin influences avoidant reactions to social threat in adults with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by interpersonal dysfunction, emotional instability, impulsivity, and risk‐taking behavior. Recent research has focused on the role of oxytocin in BPD, with mixed results as regards the processing of social stimuli.

A Comparison of Mindfulness-Based Group Training and Skills Group Training in Adults With ADHD An Open Study

Objective: To compare a novel “third wave” mindfulness-based training program with an established skills training derived from dialectical behavior therapy, to reduce ADHD symptoms and improve mindfulness and self-efficacy. Method: Ninety-one adults with ADHD (combined and inattentive type, mainly medicated) were non-randomly assigned to and treated within a mindfulness-based training group (MBTG, n = 39) or a skills training group (STG, n = 52), each performed in 13 weekly 2-hr sessions. Results: General linear models with repeated measures revealed that both programs resulted in a similar reduction of ADHD symptoms, and improvement of mindfulness and self-efficacy. However, the effect sizes were in the small-to-medium range. A decrease in ADHD symptoms ≥30% was observed in 30.8% of the MBTG participants and 11.5% of the STG participants. Conclusion: The comparatively weak results may be due to limitations such as the absence of randomization, the lack of a control group without intervention, and the lack of matching groups for borderline, depression, and anxiety status. Moreover, audio instructions for home exercises and more stringent monitoring of participants’ progress and eventual absence from sessions might have improved the outcome.

Nonverbal communication of patients with borderline personality disorder during clinical interviews: a double-blind placebo-controlled study using intranasal oxytocin.

Abstract Interpersonal dysfunction is central to borderline personality disorder (BPD). Recent research has focused on the role of oxytocin (OT) in BPD, with mixed results regarding the processing of social information. Fifteen BPD patients and 15 controls participated in two clinical interviews, one under OT and one under placebo, which were randomly conducted 1 week apart in a double-blind fashion. Nonverbal behavior was evaluated using the Ethological Coding System for Interviews. Childhood trauma was examined using the Childhood Trauma Questionnaire. The patients with BPD showed less affiliative behavior than the controls. Notably, the controls, but not the patients, displayed more affiliation when OT was given at T1 compared with OT given at T2. OT was also associated with less flight behavior in both groups when given at T1 compared with placebo. OT responses were unrelated to the patients’ history of childhood trauma. The present findings are informative with respect to patients’ nonverbal prosocial behavior in clinical settings.

Interaction of recalled parental ADHD symptoms and rearing behavior with current attachment and emotional dysfunction in adult offspring with ADHD

Research into attachment and emotion regulation has shown that children with ADHD are at risk of developing attachment disorders and emotion regulation disturbances, which in part may be due to the rearing style of their parents. No such data exists for adults with persistent ADHD. We hypothesized that current attachment style and emotion processing of adult patients with ADHD may be influenced by the presence of parental ADHD symptoms when the now adult patients were children, assuming that ADHD symptoms of parents have an impact on their parenting style. We examined recalled parental ADHD symptoms and rearing style as well as current attachment and emotion regulation abilities in a sample of 73 adults with ADHD using several self-rating instruments. Recalled prevalence of ADHD symptoms in the mother, and less so in the father, of adult patients with ADHD was significantly associated with partly adverse parental rearing styles, current attachment problems in romantic partnerships and emotion regulation disturbances compared with adult ADHD patients without possibly affected parent. ADHD symptoms in parents of children with ADHD may present a risk factor for attachment problems and poor emotion regulation when ADHD children are grown.

Effectiveness and cost of atypical versus typical antipsychotic treatment in a nationwide cohort of patients with schizophrenia in Germany.

Abstract This study investigates the effectiveness and cost of typical versus atypical antipsychotics in a nationwide German cohort of patients with schizophrenia. The study sample consisted of patients insured with 4 sickness funds (n = 8,610) who were followed up for 12 months after hospital discharge with a diagnosis of schizophrenia in 2003. Multivariate regression models were fitted to assess the relationship between outcome variables (rehospitalization, bed-days, prescriptions against adverse effects, cost) and medication type, sex, age, and severity. Severity was assessed by prior bed-days due to schizophrenia during 2000 to 2002. Risk of rehospitalization did not differ between groups but within each group severity (P = 0.0003). Males (P = 0.0016) and patients younger than 35 years (P < 0.0001) had a higher risk of rehospitalization. Number of bed-days was lower for treatment with typicals compared with atypicals (P < 0.0001); furthermore, bed-days depended on severity of disease (P < 0.0001). Prescriptions of drugs against extrapyramidal symptoms, anxiety, and agitation were higher for patients treated with typicals (P < 0.0001 for each). Mean predicted treatment cost per year was &OV0556;6442 for atypicals versus &OV0556;;4443 for typicals (P < 0.0001). This study does not support unconditional superiority of atypicals over typicals, neither in terms of effectiveness nor in terms of cost.

Alterations of Monetary Reward and Punishment Processing in Chronic Cannabis Users: An fMRI Study

Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (n = 15) and in healthy control subjects (n = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were – in contrast to healthy controls – not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.

Probabilistic reward learning in adults with Attention Deficit Hyperactivity Disorder—An electrophysiological study

Attention Deficit Hyperactivity Disorder (ADHD) is hypothesized to be characterized by altered reinforcement sensitivity. The main aim of the present study was to assess alterations in the electrophysiological correlates of monetary reward processing in adult patients with ADHD of the combined subtype. Fourteen adults with ADHD of the combined subtype and 14 healthy control participants performed an active and an observational probabilistic reward-based learning task while an electroencephalogramm (EEG) was recorded. Regardless of feedback valence, there was a general feedback-related negativity (FRN) enhancement in combination with reduced learning performance during both active and observational reward learning in patients with ADHD relative to healthy controls. Other feedback-locked potentials such as the P200 and P300 and response-locked potentials were unaltered in the patients. There were no significant correlations between learning performance, FRN amplitudes and clinical symptoms, neither in the overall group involving all participants, nor in patients or controls considered separately. This pattern of findings might reflect generally impaired reward prediction in adults with ADHD of the combined subtype. We demonstrated for the first time that patients with ADHD of the combined subtype show not only deficient active reward learning but are also impaired when learning by observing other people׳s outcomes.

Exploring the effectiveness of combined mentalization‐based group therapy and dialectical behaviour therapy for inpatients with borderline personality disorder – A pilot study

OBJECTIVES Borderline personality disorder (BPD) is characterized by emotional instability, interpersonal dysfunction, and other features that typically develop before a background of insecure attachment and traumatic experiences. Dialectical behaviour therapy (DBT) has proven highly effective in reducing self-harm and improving emotion regulation, whereby problems concerning social cognition, which are also characteristic of BPD, may need additional approaches such as mentalization-based treatment (MBT). METHODS Here, we examined, in a pilot study, the effectiveness of MBT given adjunct to DBT, compared to DBT alone, in an inpatient sample with BPD, whereby mentalization was measured using a novel cartoon-based task. RESULTS Both treatments were highly effective in reducing symptom severity. The combination of DBT and MBT was superior in reducing fearful attachment and in improving affective mentalizing. CONCLUSIONS Mentalization-based treatment in combination with DBT may improve certain aspects of social cognitive skills and attachment security, as compared to DBT alone, although the exact mechanisms that led to these changes need to be studied further. PRACTITIONER POINTS Clinical implications Dialectical behaviour therapy (DBT) can usefully be combined with mentalization-based treatment (MBT). The combination of DBT and MBT reduces self-harm more than DBT alone. DBT plus MBT may lead to a reduction in fearful attachment and improvement of affective mentalizing. Short-term combinations of evidence-based borderline treatments may enrich psychiatric inpatient care. Therefore, such approaches deserve further research. Limitations The treatment condition was therapeutically more intense than the control condition. The study lacked a follow-up assessment. The impact of comorbid conditions on treatment response was not taken into account. Adherence to the manualized approach was not measured.