Cognitive and emotional empathy in individuals at clinical high risk of psychosis.

BACKGROUND: Impairments of social cognition are considered core features of schizophrenia and are established predictors of social functioning. However, affective aspects of social cognition including empathy have far less been studied than its cognitive dimensions. The role of empathy in the development of schizophrenia remains largely elusive. METHODS: Emotional and cognitive empathy were investigated in large sample of 120 individuals at Clinical High Risk of Psychosis (CHR-P) and compared with 50 patients with schizophrenia and 50 healthy controls. A behavioral empathy assessment, the Multifaceted Empathy Test, was implemented, and associations of empathy with cognition, social functioning, and symptoms were determined. RESULTS: Our findings demonstrated significant reductions of emotional empathy in individuals at CHR-P, while cognitive empathy appeared intact. Only individuals with schizophrenia showed significantly reduced scores of cognitive empathy compared to healthy controls and individuals at CHR-P. Individuals at CHR-P were characterized by significantly lower scores of emotional empathy and unspecific arousal for both positive and negative affective valences compared to matched healthy controls and patients with schizophrenia. Results also indicated a correlation of lower scores of emotional empathy and arousal with higher scores of prodromal symptoms. CONCLUSION: Findings suggest that the tendency to 'feel with' an interaction partner is reduced in individuals at CHR-P. Altered emotional reactivity may represent an additional, early vulnerability marker, even if cognitive mentalizing is grossly unimpaired in the prodromal stage. Different mechanisms might contribute to reductions of cognitive and emotional empathy in different stages of non-affective psychotic disorders and should be further explored.

[DGPPN recommendations on quality indicators for schizophrenia]. / Aktuelle Empfehlungen der DGPPN für Schizophrenie-Qualitätsindikatoren.

BACKGROUND: In Germany, several quality indicators have been proposed for the measurement of quality of mental healthcare. Some of these quality indicators have been tested in feasibility studies. The German Association for Psychiatry and Psychotherapy (DGPPN) established the "Task Force Quality Indicators (QI)" that, based on previous experience in the development and pilot testing of indicators, considered the further development and practical realization of QI for schizophrenia. AIM: The aim was to select a set of QI for schizophrenia that can also be applied to other diagnoses or used in generic measurements. Another goal was to focus on high feasibility of indicators. METHODS: In a multistage selection process, the DGPPN Task Force selected QI that focus on essential quality aspects from an inventory of 161 existing QI developed by national and international research groups. Indicators were adapted in consultation with the "trialogic forum" of the DGPPN. RESULTS: The DGPPN proposes the following ten indicators for quality measurement in mental healthcare for schizophrenia: QI1 Long-term treatment/Monitoring of side effects, QI2 Seclusion and restraint, QI3 Number of suicides, QI4 Psychoeducational-oriented intervention for significant others, QI5 Timely beginning of outpatient treatment after discharge from inpatient treatment, QI6 Aggression management - inpatient treatment, QI7 Diagnostic procedures/Physical examination, QI8 Antipsychotic polypharmacy, QI9 Rehabilitation/Vocational rehabilitation, QI10 Diagnostic procedures/Psychosocial functioning. DISCUSSION: Most of our proposed QI have to be measured by means of additional data documentation. Based on prior experience in the pilot testing of QI, the DGPPN estimates that the additional efforts in data documentation would be manageable, but have to be refinanced. The indicators will be tested in feasibility studies in different mental healthcare hospitals in Germany.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Evaluation of the 'Jumping to conclusions' bias in different subgroups of the at-risk mental state: from cognitive basic symptoms to UHR criteria.

BACKGROUND: Patients with psychosis display the so-called 'Jumping to Conclusions' bias (JTC) - a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in 'at-risk mental state' (ARMS) patients, specifically in ARMS samples fulfilling 'ultra-high risk' (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups. METHOD: In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument - Adult Version (SPI-A). RESULTS: The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement. CONCLUSIONS: Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. / Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen.

Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.

[Assessment of quality indicators with routine data: Presentation of a feasibility test in ten specialist clinics for psychiatry and psychotherapy]. / Erhebung von Qualitätsindikatoren anhand von Routinedaten : Darstellung eines Machbarkeitstests in 10 Fachkliniken für Psychiatrie und Psychotherapie.

BACKGROUND: Prior to nationwide implementation, the feasibility of newly developed quality indicators must be assessed. The aim of this multicenter feasibility test was an evaluation of the measurability of cross-sectoral quality indicators for depression and schizophrenia by means of routine data. METHODS: The feasibility of the quality indicators was assessed in ten specialist clinics for psychiatry and psychotherapy by means of retrospective analyses of anonymous routine data. The data were extracted from the routine clinical documentation of the hospital information systems and the data from the admission and discharge sheets of the basic documentation in psychiatry (BADO) were additionally used for some clinics. Analyses were conducted for all cases of adults diagnosed with depression or schizophrenia within predefined assessment periods. RESULTS: In total five indicators for depression and nine indicators for schizophrenia were assessed and evaluated as measurable or measurable to a limited extent, sometimes with slight adaptations in the operationalization of the indicator. Due to variations in documentation, some indicators could not be calculated for all clinics. Most indicators could be collated with the data from the BADO. CONCLUSION: An assessment of indicators that measure quality-relevant aspects of care in depression and schizophrenia, is partially feasible by means of current routine data documentation analysis from the participating clinics. However, differing documentation methodologies in the participating clinics impeded a uniform assessment; therefore, for the implementation of nationwide minimum standards for the quality assurance of mental healthcare, a uniform cross-sectoral documentation methodology should be adapted to consensus and relevant quality indicators. The BADO appears to be a suitable instrument for this purpose.

Evaluation of an integrated care program for schizophrenia: concept and study design.

Concept and design of an independent scientific evaluation of different pathways of care for schizophrenia patients in Germany with respect to effectiveness and efficiency are presented. In this prospective, observational study, schizophrenia patients receiving an integrated care treatment, the intervention group (IG), are compared with patients under routine care conditions treated by the same physician (first control group, CG 1). A second control group (CG 2) of patients treated by office-based psychiatrists not participating in the integrated care program will be recruited and their data compared with the two other groups. The total amount of psychiatric hospital days after 12 months is defined as primary outcome parameter. Secondary outcome parameters comprise the frequency of psychiatric inpatient readmissions, severity of schizophrenia symptoms, remission rates and quality of life. Patients undergo assessments at baseline, month 6 and 12 using standardized and experimental questionnaires. Routine data of a regional German social health insurance fund complement information on included patients. Additionally, a cost-effectiveness and cost-utility analysis will be performed. Until now, 137 psychiatrists included 980 patients in the integrated care project in Lower Saxony, Germany, and 47 psychiatrists (IG and both CGs) are willing to participate in the independent evaluation. For the first time, a prospective observational controlled evaluation study of a countrywide integrated care project planning to recruit 500 schizophrenia patients has started using comprehensive assessments as well as routine data of a social health insurance fund.

Influence of DGKH variants on amygdala volume in patients with bipolar affective disorder and schizophrenia.

The diacylglycerol kinase eta (DGKH) gene, first identified in a genome-wide association study, is one of the few replicated risk genes of bipolar affective disorder (BD). Following initial positive studies, it not only was found to be associated with BD but also implicated in the etiology of other psychiatric disorders featuring affective symptoms, rendering DGKH a cross-disorder risk gene. However, the (patho-)physiological role of the encoded enzyme is still elusive. In the present study, we investigated primarily the influence of a risk haplotype on amygdala volume in patients suffering from schizophrenia or BD as well as healthy controls and four single nucleotide polymorphisms conveying risk. There was a significant association of the DGKH risk haplotype with increased amygdala volume in BD, but not in schizophrenia or healthy controls. These findings add to the notion of a role of DGKH in the pathogenesis of BD.

Obsessive-compulsive symptoms in at-risk mental states for psychosis: associations with clinical impairment and cognitive function.

OBJECTIVE: Obsessive-compulsive symptoms (OCS) constitute a major comorbidity in schizophrenia. Prevalence estimations of OCS for patients with at-risk mental states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or without comorbid OCS differ regarding general psychosocial functioning, psychotic and affective symptoms and neurocognitive abilities. METHOD: At-risk mental states patients (n = 233) from the interventional trial PREVENT (Secondary Prevention of Schizophrenia) were stratified according to the presence or absence of comorbid OCS and compared on several clinical variables. RESULTS: Patients, who fulfilled the criteria for obsessive-compulsive disorder (OCD) or presented with subclinical OCS (ARMSposOCS sample), did not significantly differ from patients without OCS (ARMSnegOCS) with regard to gender, age, premorbid verbal intelligence and levels of education. Furthermore, similar severity of depressive syndromes, basic cognitive, attenuated psychotic and brief limited intermittent psychotic symptoms were found. However, ARMSposOCS patients showed more impairment of psychosocial functioning and higher general psychopathology. In contrast, they scored higher in cognitive tasks measuring working memory and immediate verbal memory. CONCLUSION: Findings extend upon previous results due to the multidimensional assessment. Subsequent longitudinal studies might elucidate how comorbid OCS influence differential treatment response, especially to cognitive behavioural interventions and the transition rates to psychosis.

[National and international schizophrenia guidelines. Update 2013 regarding recommendations about antipsychotic pharmacotherapy]. / Nationale und internationale Leitlinien zur Schizophrenie. Update 2013 zum Stand der Empfehlungen zur antipsychotischen Medikation.

Treatment guidelines provide evidence-based recommendations for diagnosis and treatment to assist clinicians, care givers and patients in finding an optimized treatment option in given clinical situations. Specific treatment guidelines for schizophrenia issued by the German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and published under the auspices of the Working Group for Scientific Medical Specialist Societies (AWMF) (i.e. fulfilling the highest quality standards at the S3 level) have been available in Germany since 2006. Currently, a comprehensive revision process is ongoing to update these guidelines with the aim to publish the revision before 2014. However, since publication of the German treatment guidelines many clinical trials and meta-analyses have been published which appear to make a new evaluation of antipsychotic drug treatment necessary. Currently available national and international guidelines, such as the WFSBP, PORT and NICE guidelines, place less emphasis on the general superiority of atypical antipsychotic medication but support the idea to evaluate antipsychotic drugs based on the side effect profiles. The present overview discusses the recent guidelines development processes regarding schizophrenia and compares the available German treatment guidelines with recently published international guidelines. Current developments and issues for discussion are described in detail to provide possible implications for changes in treatment recommendations.

[Developmental process of DGPPN quality indicators]. / Entwicklungsprozess der DGPPN-Qualitätsindikatoren.

BACKGROUND: Valid and feasible quality indicators can measure healthcare quality and show potential for improvement in care. The German Association for Psychiatry and Psychotherapy (DGPPN) has developed trans-sectoral quality indicator sets for four mental disorders with high prevalence (alcohol dependence, dementia, depression and schizophrenia). MATERIAL AND METHOD: The DGPPN followed a structured multistage process and used guideline recommendations and the results of systematic evidence searches as the basis for the development of these quality indicators. This was followed by a structured consensus process for all quality indicators. RESULTS: Four evidence and consensus-based, diagnosis-specific and trans-sectoral quality indicator sets have been developed. CONCLUSION: It is possible to develop quality indicators on the basis of guideline recommendations. The implementation of the DGPPN quality indicators will play a crucial role in order to evaluate their utility and feasibility as quality measures for German mental healthcare.

Comorbid substance abuse in first-episode schizophrenia: effects on cognition and psychopathology in the EUFEST study.

UNLABELLED: Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients. METHOD: In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding. RESULTS: In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption. CONCLUSIONS: FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.

The DTNBP1 (dysbindin-1) gene variant rs2619522 is associated with variation of hippocampal and prefrontal grey matter volumes in humans.

DTNBP1 is one of the most established susceptibility genes for schizophrenia, and hippocampal volume reduction is one of the major neuropathological findings in this severe disorder. Consistent with these findings, the encoded protein dysbindin-1 has been shown to be diminished in glutamatergic hippocampal neurons in schizophrenic patients. The aim of this study was to investigate the effects of two single nucleotide polymorphisms of DTNBP1 on grey matter volumes in human subjects using voxel-based morphometry. Seventy-two subjects were included and genotyped with respect to two single nucleotide polymorphisms of DTNBP1 (rs2619522 and rs1018381). All participants underwent structural magnetic resonance imaging (MRI). MRI data were preprocessed and statistically analysed using standard procedures as implemented in SPM5 (Statistical Parametric Mapping), in particular the voxel-based morphometry (VBM) toolbox. We found significant effects of the DTNBP1 SNP rs2619522 bilaterally in the hippocampus as well as in the anterior middle frontal gyrus and the intraparietal cortex. Carriers of the G allele showed significantly higher grey matter volumes in these brain regions than T/T homozygotes. Compatible with previous findings on a role of dysbindin in hippocampal functions as well as in major psychoses, the present study provides first direct in vivo evidence that the DTNBP1 SNP rs2619522 is associated with variation of grey matter volumes bilaterally in the hippocampus.

Transcranial brain stimulation in schizophrenia: targeting cortical excitability, connectivity and plasticity.

Transcranial magnetic stimulation (TMS) is a very popular tool used within neuroscience. This and other associated techniques allow the in vivo investigation of cortical excitability, cortical connectivity and cortical plasticity. Schizophrenia is a brain disorder and various theories other than the dopamine hypothesis have been developed to describe its underlying neurobiology. Supported by animal and post mortem studies, findings from TMS studies indicate that schizophrenia is a disease of reduced cortical inhibition and impaired intra- and intercortical connectivity. Further studies using repetitive TMS and other plasticity-inducing techniques have shown that cortical plasticity is altered in schizophrenia patients, supporting the recently discussed plasticity deficiency theory of schizophrenia. This review gives an introduction to the most frequently applied techniques, describes findings in schizophrenia patients and discusses these findings with regard to the neurotransmitters and associated receptors involved. In summary, there is emerging evidence of an important pathophysiological interplay between reduced inhibition, impaired connectivity and reduced plasticity in schizophrenia patients. Gamma-aminobutyric-acid-receptors and glutamtergic N-Methyl-D-aspartic-acid-receptors are most likely to be involved in this complex interplay, which may reflect a disturbed signal-to-noise ratio in schizophrenia patients. This review will discuss this issue with regard to the available treatment options and will give implications for future research and therapeutic strategies regarding disinhibition and neuroplasticity in schizophrenia.

DISC1 (disrupted-in-schizophrenia 1) is associated with cortical grey matter volumes in the human brain: a voxel-based morphometry (VBM) study.

DISC1 (Disrupted-In-Schizophrenia 1), one of the top candidate genes for schizophrenia, has been associated with a range of major mental illnesses over the last two decades. DISC1 is crucially involved in neurodevelopmental processes of the human brain. Several haplotypes and single nucleotide polymorphisms of DISC1 have been associated with changes of grey matter volumes in brain regions known to be altered in schizophrenia and other psychiatric disorders. The aim of the present study was to investigate the effects of two single nucleotide polymorphisms (SNPs) of DISC1 on grey matter volumes in human subjects using voxel-based morphometry (VBM). 114/113 participating subjects (psychiatric patients and healthy controls) were genotyped with respect to two at-risk SNPs of DISC1, rs6675281 and rs821616. All participants underwent structural magnetic resonance imaging (MRI). MRI data was statistically analyzed using voxel-based morphometry. We found significant alterations of grey matter volumes in prefrontal and temporal brain regions in association with rs6675281 and rs821616. These effects of DISC1 polymorphisms on brain morphology provide further support for an involvement of DISC1 in the neurobiology of major psychiatric disorders such as schizophrenia.

Innovative treatment approaches in schizophrenia enhancing neuroplasticity: aerobic exercise, erythropoetin and repetitive transcranial magnetic stimulation.

Schizophrenia is a brain disorder associated with subtle, but replicable cerebral volume loss mostly prevalent in frontal and temporal brain regions. Post-mortem studies of the hippocampus point to a reduction of the neuropil constituting mainly of synapses associated with changes of molecules mediating plastic responses of neurons during development and learning. Derived from animal studies interventions to enhance neuroplasticity by inducing adult neurogenesis, synaptogenesis, angiogenesis and long-term potentiation (LTP) were developed and the results translated into clinical studies in schizophrenia. Out of these interventions aerobic exercise has been shown to increase hippocampal volume, elevate N-acetyl-aspartate in the hippocampus as neuronal marker, and improve short-term memory in schizophrenia. The hematopoietic growth factor erythropoetin (EPO) is involved in brain development and associated with the production and differentiation of neuronal precursor cells. A first study demonstrated a positive effect of EPO application on cognition in schizophrenia patients. In randomised controlled studies with small sample size, the efficacy of repetitive transcranial magnetic stimulation (rTMS), a biological intervention focussing on the enhancement of LTP, has been shown for the improvement of positive and negative symptoms in schizophrenia,. The putative underlying neurobiological mechanisms of these interventions including the role of neurotrophic factors are outlined and implications for future research regarding neuroprotection strategies to improve schizophrenia are discussed.

[Response and remission in schizophrenic subjects]. / Response und Remission bei an Schizophrenie erkrankten Patienten.

BACKGROUND: This naturalistic study investigates in detail symptom reduction during acute inpatient treatment (response), long-term symptom improvement in the post-acute phase (remission) and the rate of re-hospitalisations. MATERIAL AND METHODS: A total of 183 patients were enrolled. Criteria for response were PANSS total score and syndrome reductions of 20, 30, 40 and 50%. Remission criteria employed were based on recommendations from Andreasen et al. RESULTS: The average length of stay was 45.6 days (SD 42.7). PANSS total score response rates were found to be 63.9% for the 20% level and were reduced in the following consecutive levels by approximately 15%. Only 10.3% of the patients remitted during a 1-year follow-up period. At least one re-hospitalisation was reported for 43.9% of the subjects. CONCLUSION: Compared to previous randomised and controlled trials, the rates of response and remission are significantly lower. In daily inpatient care, the chronic course of schizophrenia is far commoner than expected from previous reports.

[Guideline intentions of the German Society of Psychiatry, Psychotherapy and Nervous Diseases (DGPPN)]. / Leitlinienintentionen der DGPPN.

The practice guidelines of the German Society of Psychiatry, Psychotherapy and Nervous Diseases (DGPPN) include systematically developed and evidence-based treatment recommendations which assist clinicians and patients in making decisions about appropriate treatment for specific conditions. The intentions of practice guidelines are to improve the quality of care and the outcome of mental diseases. This paper describes the methodology behind the development of the guidelines and lists the already existing practice guidelines as well as the guidelines actually being developed. In addition, it is outlined how quality indicators may be derived from guidelines. A major aim of the German Society of Psychiatry, Psychotherapy and Nervous Diseases (DGPPN) is to assure the quality of inpatient and outpatient care of the mentally ill by developing evidence-based consensus guidelines.