Bastian Wollweber

Clinical characteristics and treatment outcome in a representative sample of depressed inpatients – Findings from the Munich Antidepressant Response Signature (MARS) project

Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.

Impulse pattern in bi-directionally coupled model neurons of different dynamics.

The effects of bi-directional gap junction coupling of two model neurons with subthreshold oscillations have been examined when the individual neurons are operating at different dynamical states either in the tonic or bursting firing mode. Our simulations indicate that intermediate coupling strengths mostly lead to highly variable, often chaotic impulse patterns whereas transition to completely synchronized activity at high coupling strengths is generally going along with transitions to regular limit cycle activity. The synchronized activity pattern, however, can be completely different from the original pattern of the uncoupled neurons.

Affective temperaments and residual symptoms in patients with mood and anxiety disorders

Objective. Temperament conventionally refers to stable behavioural and emotional reactions that appear early in life and are influenced in part by genetic constitution. Few studies compared temperamental traits in anxiety and mood disorders even though some authors suggested a clinical and neurobiological continuum between them. The aim of the study was to compare temperamental traits and psychopathological dimensions in subjects with DSM-IV diagnoses of mood and anxiety disorders. Methods. A total of 101 clinically stabilized consecutive outpatients (45 subjects with anxiety disorders and 56 with mood disorders diagnoses) were evaluated. The brief version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego (briefTEMPS-M) and Symptom Checklist-90 (SCL-90) were used to assess temperamental traits and psychopathological dimensions, respectively. Results. No significant differences between anxiety disorders and mood disorders subjects for TEMPS-M or SCL-90 mean scores were observed. Different TEM...Objective. Temperament conventionally refers to stable behavioural and emotional reactions that appear early in life and are influenced in part by genetic constitution. Few studies compared temperamental traits in anxiety and mood disorders even though some authors suggested a clinical and neurobiological continuum between them. The aim of the study was to compare temperamental traits and psychopathological dimensions in subjects with DSM-IV diagnoses of mood and anxiety disorders. Methods. A total of 101 clinically stabilized consecutive outpatients (45 subjects with anxiety disorders and 56 with mood disorders diagnoses) were evaluated. The brief version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego (briefTEMPS-M) and Symptom Checklist-90 (SCL-90) were used to assess temperamental traits and psychopathological dimensions, respectively. Results. No significant differences between anxiety disorders and mood disorders subjects for TEMPS-M or SCL-90 mean scores were observed. Different TEMPS-M scores differentially affect residual clinical symptoms. Conclusions. Our data represent an indirect indicator of possible common diathesis between the two different disorders. The temperament “paradigm” could explain part of the residual symptomatology. The evaluation of affective temperaments seems to add considerable clinical information to psychopathological and diagnostic descriptions.

PTSD psychotherapy improves blood pressure but leaves HPA axis feedback sensitivity stable and unaffected: first evidence from a pre-post treatment study

Although key to development of tailored drugs for augmentation treatment of psychotherapy for posttraumatic stress disorder (PTSD), the biological correlates of PTSD remission are still unknown, probably because pre-post treatment studies searching for them are rare. Not even the feedback sensitivity of the otherwise well-studied hypothalamic-pituitary-adrenal (HPA) axis nor arterial blood pressure (BP), which was previously reported to be elevated in PTSD patients, have so far been analyzed during PTSD treatment. To narrow this knowledge gap, we first performed an overnight dexamethasone suppression test (DST) in a mixed-sex cohort of 25 patients with severe PTSD vs. 20 non-traumatized healthy controls (nt-HC). In addition to hormones, BP and heart rate (HR) were measured at each of the four assessment points (APs). Second, the same parameters were assessed again in 16 of these patients after 12 sessions of integrative trauma-focused cognitive behavioral therapy (iTF-CBT). In relation to nt-HC, PTSD patients showed a significant elevation in HR and diastolic BP while their systolic BP, DST outcomes and basal serum cortisol levels (BSCL) were not significantly altered. In response to iTF-CBT, PTSD symptoms and dysfunctional stress coping strategies improved significantly in PTSD patients. Most important, also their systolic and diastolic BP levels ameliorated at distinct APs while their DST outcomes and BSCL remained unchanged. To our knowledge, this is the first pre-post treatment study assessing the stability of the DST outcome and BP levels during PTSD treatment. Our results provide first evidence for a non-involvement of HPA axis feedback sensitivity in PTSD symptom improvement and, furthermore, suggest a possible role for BP-regulating pathways such as the sympathetic nervous system in PTSD remission. Limitations arise from the small sample size, the lack of an untreated patient group and drug treatment of patients.

Improvement of nonsuicidal self-injury following treatment with antipsychotics possessing strong D1 antagonistic activity: evidence from a report of three cases

Introduction: There is no drug treatment for nonsuicidal self-injury (NSSI), a highly prevalent and burdensome symptom of several psychiatric diseases like posttraumatic stress disorder (PTSD), personality disorders, and major depression (MD). Methods: Here, we present a retrospective series of three patients demonstrating a persistent remission in MD-associated NSSI in response to treatment with antipsychotics possessing marked D1 receptor antagonistic activity. Results: To the best of the authors’ knowledge, the case series presented is only the second clinical paper suggesting a role for D1 antagonists in NSSI drug therapy. Conclusions: Together with previously published data from rodent models, the findings suggest a role for D1 antagonists in NSSI drug therapy and hence for the D1 receptor in NSSI pathogenesis. This conclusion is limited by the facts that the patients presented here received polypharmacy and that the D1 receptor antagonistic antipsychotics suggested here as effective ‘anti-auto-aggressants’ do not address D1 receptors only but multiple neurotransmitter receptors/systems.

Pathophysiology of Sleep Disorders

Current concepts on neurobiological mechanisms underlying sleep disorders such as insomnia, narcolepsy, and restless legs syndrome/periodic limb movement disorder are being reviewed in this chapter, which includes short discussions of clinical key features, diagnostic criteria, and therapeutic aspects of these disorders. Chronic insomnia is a common and complex 24-h disorder that derives from a multifactorial interaction of biological and psychological factors affecting both sleep and wakefulness. Several models of the pathophysiology of insomnia have been elaborated, but no single underlying pathophysiological process has been shown to represent a causal factor. Importantly, persistent insomnia has been identified as a risk factor for the development or exacerbation of certain psychiatric conditions. Narcolepsy is characterized by excessive daytime sleepiness and cataplexy. Its pathophysiology is largely associated with hypocretin ligand deficiency possibly caused by the postnatal loss of hypocretin-containing neurons. An immune-mediated etiology for hypocretin deficiency has been suggested. Sleep-related movement disorders include the restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). Pharmacological, neuroimaging, and electrophysiological studies suggest a dysfunction of the supraspinal inhibitory system triggering RLS and PLMD. In addition, recent studies suggest a strong genetic contribution to both disorders. Further research on sleep disorders is expected to guide new treatment strategies.