Anne Karow

Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia

Objective:  Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia.

Cooperative binding of ATP and RNA induces a closed conformation in a DEAD box RNA helicase

RNA helicases couple the energy from ATP hydrolysis with structural changes of their RNA substrates. DEAD box helicases form the largest class of RNA helicases and share a helicase core comprising two RecA-like domains. An opening and closing of the interdomain cleft during RNA unwinding has been postulated but not shown experimentally. Single-molecule FRET experiments with the Bacillus subtilis DEAD box helicase YxiN carrying donor and acceptor fluorophores on different sides of the interdomain cleft reveal an open helicase conformation in the absence of nucleotides, or in the presence of ATP, or ADP, or RNA. In the presence of ADP and RNA, the open conformation is retained. By contrast, cooperative binding of ATP and RNA leads to a compact helicase structure, proving that the ATP- and ADP-bound states of RNA helicases display substantially different structures only when the RNA substrate is bound. These results establish a closure of the interdomain cleft in the helicase core at the beginning of the unwinding reaction, and suggest a conserved mechanism of energy conversion among DEAD box helicases across kingdoms.

The mechanism of ATP-dependent RNA unwinding by DEAD box proteins

Abstract DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA (dsRNA). In addition, they facilitate protein displacement and remodeling of RNA or RNA/protein complexes. Their hallmark feature is local destabilization of RNA duplexes. Here, we summarize current data on the DEAD box protein mechanism and present a model for RNA unwinding that integrates recent data on the effect of ATP analogs and mutations on DEAD box protein activity. DEAD box proteins share a conserved helicase core with two flexibly linked RecA-like domains that contain all helicase signature motifs. Variable flanking regions contribute to substrate binding and modulate activity. In the presence of ATP and RNA, the helicase core adopts a compact, closed conformation with extensive interdomain contacts and high affinity for RNA. In the closed conformation, the RecA-like domains form a catalytic site for ATP hydrolysis and a continuous RNA binding site. A kink in the backbone of the bound RNA locally destabilizes the duplex. Rearrangement of this initial complex generates a hydrolysis- and unwinding-competent state. From this complex, the first RNA strand can dissociate. After ATP hydrolysis and phosphate release, the DEAD box protein returns to a low-affinity state for RNA. Dissociation of the second RNA strand and reopening of the cleft in the helicase core allow for further catalytic cycles.

Subjective well-being under neuroleptic treatment and its relevance for compliance

Objective:  To review the concept of ‘subjective well‐being under neuroleptic treatment’, its development and clinical relevance, particularly regarding compliance.

Health‐related quality of life in blepharospasm or hemifacial spasm

Objectives –  Health‐related quality of life (HRQL) has become an important outcome criterion of medical interventions, but was hardly studied in patients with facial spasms.

Rationale and content of psychenet: the Hamburg Network for Mental Health

With the public-funded research and development project psychenet: the Hamburg Network for Mental Health (2011–2014), the Federal Ministry of Education and Research contributes to strengthening healthcare regions in Germany by establishing new trans-sectoral cooperations and implement and evaluate selected innovations. More than 60 partners from research, health care, health industry and government in the Free and Hanseatic City of Hamburg are promoting innovative measures to improve the treatment for mental disorders. The main objective is to implement integrated healthcare networks based on evidence for effective treatment methods, deriving from high-quality research throughout five indications such as psychosis, depression, somatoform and functional syndromes, anorexia and bulimia and addiction illnesses in adolescence. Those networks are accompanied by additional measures, for example, for improving information and education, addressing occupational health or strengthening the participation of patients and their families suffering from mental illness.

Remitted but still impaired? Symptomatic versus functional remission in patients with schizophrenia.

INTRODUCTION Studies reported close associations between functional outcome and symptomatic remission as defined by the Remission in Schizophrenia Working Group. This observational study was aimed at the investigation of deficits in daily functioning, symptoms and subjective well-being in remitted and non-remitted patients with schizophrenia. METHODS Symptoms (PANSS), functional outcome (FROGS, GAF), subjective well-being (SWN-K) and other characteristics were assessed in 131 patients with schizophrenia (DSM-IV) within the European Group on Functional Outcomes and Remission in Schizophrenia (EGOFORS) project. RESULTS A significant better level of functioning was measured for remitted versus non-remitted patients, though remitted patients still showed areas with an inadequate level of functioning. Functional deficits were most often seen in social relations (40%), work (29%) and daily life activities (17%). Best functioning was assessed for self-care, self-control, health management and medical treatment. A moderate to severe level of disorganization and emotional distress was observed in 38% and impaired subjective well-being in 29% of patients defined as being in symptomatic remission. DISCUSSION The results confirm a close association between symptomatic remission and functional outcome. However, deficits in different areas of functioning, symptoms and well-being underline the need for combined outcome criteria for patients with schizophrenia.

Insight and quality of life in schizophrenia: recent findings and treatment implications.

Purpose of review Several studies have reported that patients with schizophrenia lack awareness of having a mental disorder or symptoms of a mental disorder. The concept of insight has long been considered important for engagement in treatment, psychotherapeutic progress and good prognosis. Recent findings Contradictory results were found regarding the relationship between insight into illness and quality of life in patients with schizophrenia. Although previous studies found an inverse or no significant association, recent studies reported that greater insight into illness is significantly associated with an increase in depression and poor subjective quality of life. Summary Patients with good insight might realize their restrictions more clearly. The stigma of being mentally ill and the need for treatment or hospitalization are serious psychological strains. The increase of depression and suicidal ideation and decrease in subjective quality of life in patients with better insight underline the importance of insight for the clinical course in schizophrenia. The inclusion of modules focussing on depressive symptoms and quality of life-related aspects to psychoeducational programmes, as well as a greater awareness of the physician for these questions and a strengthening of the therapeutic alliance, might help improve insight without the risk of deteriorating mood and quality of life.

Dissociative symptoms in patients with schizophrenia: relationships with childhood trauma and psychotic symptoms

OBJECTIVE This study sought to examine the stability of dissociative symptoms in patients with schizophrenia spectrum disorders as well as relationships between psychotic symptoms, childhood trauma, and dissociation. METHOD One hundred forty-five patients with schizophrenia spectrum disorders (72% schizophrenia, 67% men) were examined at admission to inpatient treatment and 3 weeks later using the Positive and Negative Syndrome Scale, the Childhood Trauma Questionnaire, and the Dissociative Experiences Scale. RESULTS Dissociative symptoms significantly decreased over time (mean, 19.2 vs 14.1; P < .001). The best predictor of dissociative symptoms at admission was the Positive and Negative Syndrome Scale positive subscale (F(inc)(3,64) = 3.66, P = .017), whereas childhood sexual abuse best predicted dissociation when patients were stabilized (F(inc)(10,80) = 2.00, P = .044). CONCLUSION Dissociative symptoms in patients with schizophrenia spectrum disorders are related to childhood trauma. Dissociation seems to be state dependent in this diagnostic group. Moreover, diagnostic interviews, in addition to the Dissociative Experiences Scale, should be considered to avoid measurement artifacts.

Beyond the Usual Suspects: Positive Attitudes Towards Positive Symptoms Is Associated With Medication Noncompliance in Psychosis

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.