Adverse effects of cognitive behavioral therapy and cognitive remediation in schizophrenia: results of the treatment of negative symptoms study.

This study examined the frequency and extent of detrimental effects of cognitive behavioral therapy (CBT) for psychosis. In a randomized clinical trial, we investigated the efficacy of CBT for the reduction of negative symptoms as compared with cognitive remediation (CR) in schizophrenia patients (n = 198). Safety was addressed through assessment of severe adverse events (SAEs), which were defined as suicides, suicide attempts, suicidal crises, and severe symptom exacerbations over a period of 12 months after inclusion in the study. Monthly assessments with Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms allowed for the analysis of symptom increases during the treatment. There were no suicides in the trial. SAEs were observed in 10 CBT and 5 CR patients. Increases in negative symptoms occurred in 64 CBT and 58 CR patients. These differences were not significant. The maximum increase in negative symptoms under treatment, as compared with the baseline, was equal to an effect size of -0.66 in CBT patients and -0.77 in CR patients. Thus, the SAE rate was comparable between both interventions and was relatively low, given the severity of the psychotic disorder. Therapists should be aware of a subgroup of patients who show symptom increases with large effect sizes and might require more intensive care.

Implementation of a manual-based training of humor abilities in patients with depression: a pilot study.

Humor and laughter can positively influence mood, promote optimism and lead to a change of perspective. Six patients with major depression participated in a group training program specifically designed to enhance humor abilities. After 8 weeks of training, short-term mood improvement was observed and the patients considered themselves more capable of using humor as a coping strategy. Acquired humor skills also helped to sustain the patients' motivation throughout the training period. In light of these encouraging findings, further studies to compare the effectiveness of the humor training with the effectiveness of other types of intervention and to assess its potential long-term effects seem warranted.

Quality and correlates of specific self-esteem at the beginning stabilisation phase of schizophrenia.

In view of the potential importance of self-esteem in schizophrenia, there is a considerable lack of knowledge about the characteristics of specific self-esteem. The literature suggests that the experience of the self might be particularly destabilised in the transition phase between acute and remission points of the illness. Thus, the present study aims at examining the quality and correlates of different self-concepts at the beginning stabilisation phase of schizophrenia. In this study, 135 patients with schizophrenia were assessed 3 weeks after admission to inpatient treatment. Four central self-concepts were measured by the Frankfurt Self-Concept Scales (FSKN; Deusinger, I.M., 1986, Die Frankfurter Selbstkonzeptskalen (FSKN), Göttingen, Hogrefe). Clinical psychopathologic, neuropsychological and sociodemographic factors were analysed in two-step exploratory correlation and regression analyses to determine their relative contribution to self-concepts. The median of the four self-concepts ranged between -0.9 and -1.4 standard deviations below normative level. The relationship between negative symptoms and self-concepts was consistently significant, even when the contribution of depression was partialed out. In the multivariate analyses, these two symptom clusters explained up to 39% of the variances in our patients' self-evaluation. Neuropsychological dysfunctions were of relatively subordinate relevance for the patients' self-concepts. Thus, our results suggest that specific self-esteem at the point of beginning stabilisation of schizophrenia is significantly confounded not only by depression but also by negative symptoms.

Does the cognitive dispute of psychotic symptoms do harm to the therapeutic alliance?

We examined whether the cognitive dispute of psychotic symptoms has a negative impact on the course of the therapeutic alliance. Sixty-seven patients with persistent psychotic symptoms received either cognitive behavioral therapy (CBT) or supportive therapy. Questionnaire-based alliance ratings were repeatedly obtained throughout the course of therapy. Patient and therapist alliance ratings were examined separately. Data analyses comprised repeated measurement analyses of variance and cluster analytic procedures. Neither patient nor therapist alliance ratings showed a differential course throughout the treatments. This was despite the implementation of disputing strategies in later stages of CBT. Irrespective of the treatment condition a cluster with a positive alliance rating and a cluster with a poorer rating were found for therapist and patient ratings, respectively. Baseline symptoms and insight differentiated between the types of clusters. In conclusion, CBT-specific interventions that challenge psychotic symptoms do not necessarily negatively influence the course of the alliance.

Cognitive behavioural treatment of negative symptoms in schizophrenia patients: study design of the TONES study, feasibility and safety of treatment.

Currently, there are no convincing treatment strategies for negative symptoms of schizophrenia. On this background, we are conducting the treatment of negative symptoms (TONES) study which addresses the question whether cognitive behavioural therapy (CBT) is efficacious for the reduction of negative symptoms in schizophrenia. The present paper aims at presenting the design of the clinical trial of the study as well as the treatment concept. Further, we investigate the feasibility and the safety of our study treatment. The TONES study is a multicentric, prospective, single-blind, randomised, and controlled trial (RCT). The clinical trial compares CBT (test condition) and cognitive remediation (CR; control condition) with respect to the efficacy in reducing negative symptoms. In order to systematically assess aspects of adherence and feasibility therapists filled in session reports after each session. The safety analysis is performed using the sequential method of Whitehead (The design and analysis of sequential clinical trials, Ellis Horwood, Chichester, 1983). We were able to conduct a systematic recruitment and to include a sample of N = 198 patients which is characterised by negative symptoms of medium severity. The majority of patients accepted the format of a 50-min treatment session. The manualised treatment content seemed to be adequate and the cooperation between patients and therapists was excellent or adequate in approximately 80% of the treatment sessions. Of the 15 severe adverse events 10 occurred in the CBT and 5 in the CR. This difference between the groups was not significant. The study presented here is presumably the first high quality RCT which evaluates CBT with negative symptoms as primary endpoint. On the background of the data presented we conclude that CBT for the reduction of negative symptoms is feasible and can be conducted safely.

The influence of baseline symptoms and insight on the therapeutic alliance early in the treatment of schizophrenia.

BACKGROUND: The consistent association between therapeutic alliance and outcome underlines the importance of identifying factors which predict the development of a positive alliance. However, only few studies have examined the association between pretreatment characteristics and alliance formation in patients with schizophrenia. OBJECTIVE: The study examined whether symptoms and insight would predict the therapeutic alliance in psychotherapy of schizophrenia. Further, the associations and differences between patient and therapist alliance ratings were studied. METHODS: Eighty patients with schizophrenia spectrum disorders received manual-based psychotherapy. Assessment of symptoms and insight was conducted at baseline, and questionnaire-based alliance ratings were obtained three weeks into treatment. Patient and therapist alliance ratings were examined separately. RESULTS: Patient and therapist alliance ratings were not significantly correlated (r=0.17). Patient ratings of the alliance were significantly higher than the ratings of their therapists (d=0.73). More insight in psychosis significantly predicted higher patient ratings of the alliance. Less positive and negative symptoms were significant predictors of higher therapist alliance ratings. CONCLUSION: The findings indicate that symptoms and insight have an influence on the therapeutic alliance in the treatment of schizophrenia spectrum disorders. Patients' and therapists' perceptions of the alliance do not seem to demonstrate much convergence.

[Research into the feasibility of cognitive behavioural therapy in the treatment of psychotic disorders]. / Psychotherapieforschung zur Kognitiven Verhaltenstherapie bei Positiv-Symptomen psychotischer Störungen.

Psychotherapy in psychotic disorders is a rare condition and is confronted with much scepticism. On the background of intensive research - in particular in Great Britain, sufficient empirical evidence is available from randomised clinical trials to recommend Cognitive Behavioural Treatment for routine care. However, many research questions are open. In particular, the specific efficacy compared to supportive treatment is unclear and the mechanisms of action as well as economical aspects should be investigated more intensively. The psychotherapy research network "psychotherapy of psychotic syndromes" conducts research projects on these issues. The present paper gives an overview over the treatment and the scientific concept of this network.

Development and validation of a cluster-based classification system to facilitate treatment tailoring.

AIMS: The objectives of this study were to replicate smoker profiles identified in Batra et al. (in press) and to develop a cluster-based classification system to categorize new cases into smoker profiles so that an appropriate tailored intervention could be applied. METHODS: Participants were smokers in southwest Germany who sought treatment for smoking cessation. In the first sample, discriminant analysis was used to create classification formulas for a future study (classification sample: n = 165). The second sample served to replicate the smoker profiles, which included participants reporting symptoms of hyperactivity/novelty-seeking, depressivity or high nicotine dependence as well as participants scoring low across smoking and psychological variables (replication sample: N = 134). RESULTS: Part 1 was focused on the development of formulas, using Fisher's coefficients, with which new cases could be classified. Part 2 adequately replicated previous findings concerning the smoker profiles, such that 70% of participants in the second sample were classified identically using cluster analysis and classification formulas. CONCLUSIONS: The smoker profiles found in a previous study were replicated, and a classification system was developed for a future study which will test the efficacy of tailored treatments for the different smoker profiles.

Course of cognitive functioning during the stabilization phase of schizophrenia.

The present study aimed at examining the longitudinal course of neuropsychological impairments in schizophrenia patients during the stabilization phase of the illness. Cognitive functioning of 151 schizophrenia patients was assessed at baseline, 9-month, and 15-month follow-up with a comprehensive battery of cognitive tests. Cognitive performance of 40 matched controls was also examined at baseline and follow-up in order to control for effects of repeated testing. We found significant improvements in memory, attention, and global cognitive functioning from baseline to 9-month follow-up. Abstraction was stable at a relatively normal level. Global cognitive functioning remained at 9-month follow-up one standard deviation below normative level. Improvements in patients' cognitive performance between the 9-month and the 15-month follow-up were fewer and less pronounced. The present study implies that schizophrenia is a static encephalopathy with trait and state dependent cognitive components particularly in the attention and memory domain. The statistically and clinically significant cognitive improvements should be ground for clinical optimism.

Collaboration in outpatient antipsychotic drug treatment: analysis of potentially influencing factors.

Knowledge of factors relevant for medication adherence and patient collaboration is still limited. Our study aims at exploring the contribution of a variety of factors to collaboration in outpatients with schizophrenia and schizoaffective disorder. We obtained self-rated and observer-rated data from 108 outpatients during an interview 6 months after hospital discharge. The compliance rating scale (CRS) classified 76% of the patients as collaborative. Factors related to the patient, illness, treatment, and social environment were analysed in two-step explorative correlation and regression analyses in order to determine their relative contribution to collaboration. Only trust in medication and lack of insight were associated with collaboration, and they accounted for 38% of the variance. Neither medication side effects nor neuropsychological functioning correlated with collaboration. The conceptualisation of medication adherence is complex, and there are a number of unresolved methodological problems. The data indicate that illness and treatment-related subjective attitudes may be more relevant than side effects, cognitive functioning or any sociodemographic variable.

Autoantibody reactivity in serum of patients with major depression, schizophrenia and healthy controls.

The present study assessed 25 patients with unipolar major depression and 34 patients with schizophrenia along with 50 healthy, non-psychiatric controls for the presence of serum antinuclear (ANA), smooth muscle (SMA), anti-endothelial (AEA), anti-sarcolemma (ASA), thyroid gland (TGA) and parietal cell (PCA) antibodies. In the group of patients with major depression, the frequency of elevated ANA, TGA and PCA was significantly higher than in the control group. In addition, the group of patients with schizophrenia significantly more often showed increased levels of ANA and SMA than the control group of healthy volunteers. When the two psychiatric groups were compared, PCA serum titers in major depression and SMA values in schizophrenia were significantly more frequently elevated, whereas values of AEA and ASA showed no difference. These results point towards the existence of an unspecific (auto) immune disposition or reaction in at least a subgroup of patients with major depression and schizophrenia.

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.

Multidimensional smoker profiles and their prediction of smoking following a pharmacobehavioral intervention.

The objective of this observational study was to identify multidimensional smoker profiles to aid the development of future tailored treatments for different smoker subtypes. Based on findings in the literature, it was hypothesized that smokers reporting higher levels of novelty seeking/hyperactivity, depressivity, and nicotine dependence would evince greater odds of postintervention smoking than smokers reporting lower symptom levels across these dimensions. Adult regular smokers (N=165) in southwest Germany completed self-report questionnaires assessing psychological and smoking variables and received a pharmacobehavioral intervention. A k-means cluster analysis involving indicators of depressivity, novelty seeking/hyperactivity, and nicotine dependence confirmed the hypothesized smoker profiles. These clusters evinced robustness on cross-validation and predicted smoking on follow-up. Specifically, smokers with depressive, novelty-seeking/hyperactive, and higher dependence profiles evinced significantly greater odds of smoking on follow-up than smokers with low-scoring profiles.

Altered lymphocyte distribution in Alzheimer's disease.

The contribution of immunological factors in the etiopathogenesis of Alzheimer's disease (AD) is increasingly noted. Apart from cerebral immunological findings, peripheral changes of the immune systems have been reported including lymphocyte function and subset distribution. As data still remain inconsistent, we investigated a sample of 43 patients with AD and of 34 healthy age-matched controls. Distribution of the T-, B- and NK cell subsets was determined by flow cytometry (FACS). We found a significant decrease of CD3(+) lymphocytes as well as of CD19(+) lymphocytes. A slight increase of the CD4(+) and a decrease of the CD8(+) subpopulation could be observed, without significant change of the CD4(+)/CD8(+) ratio. CD16(+)56(+) cells were not altered. Our findings of decreased T- and B-Cell numbers in AD sustain the hypothesis of a general decline of immune activity in AD. A putative association with premature immunosenescence in AD and possible pathogenetic implications are discussed.

BDNF serum and CSF concentrations in Alzheimer's disease, normal pressure hydrocephalus and healthy controls.

Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) are common forms of dementia in the elderly. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. BDNF serum and cerebrospinal fluid (CSF) concentrations were assessed by a sensitive ELISA in 27 AD patients in comparison to 9 NPH patients and 28 age-matched healthy controls (10 CSF samples). We found a significant decrease of BDNF serum concentration in AD (18.6ng/ml) and NPH patients (18.1ng/ml) as compared to healthy controls (21.3ng/ml; p=0.041/p=0.017). BDNF serum concentrations did not correlate with CSF levels, age or MMSE scores both in AD and NPH patients. In unconcentrated CSF samples, BDNF could be detected in AD patients in 8/27 cases (29.6%; mean of 4.6pg/ml), in NPH patients in 1/9 cases (11.1%; mean of 6.4pg/ml) and in the control subjects in 5/10 cases (50%; mean of 1.6pg/ml) with no significant differences as regards mean concentration and frequency of detectable BDNF in CSF. The decrease of BDNF serum levels in AD and NPH may reflect a lack of trophic support and thus contribute to progressive degeneration in both diseases. In contrast to serum, CSF seems to be no useful source to determine BDNF in AD or NPH because of too low concentrations. Further examinations have to follow to elucidate the potential sources and the meaning of reduced BDNF levels in the blood in AD and NPH.

Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants.

Fibromyalgia (FM) is still often viewed as a psychosomatic disorder. However, the increased pain sensitivity to stimuli in FM patients is not an "imagined" histrionic phenomena. Pain, which is consistently felt in the musculature, is related to specific abnormalities in the CNS pain matrix. Brain-derived neurotrophic factor (BDNF) is an endogenous protein involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system (CNS and PNS). Several lines of evidence converged to indicate that BDNF also participates in structural and functional plasticity of nociceptive pathways in the CNS and within the dorsal root ganglia and spinal cord. In the latter, release of BDNF appears to modulate or even mediate nociceptive sensory inputs and pain hypersensitivity. We were interested, if BDNF serum concentration may be altered in FM. The present pilot study assessed to our knowledge for the first time BDNF serum concentrations in 41 FM patients in comparison to 45 age-matched healthy controls. Mean serum levels of BDNF in FM patients (19.6 ng/ml; SD 3.1) were significantly increased as compared to healthy controls (16.8 ng/ml; SD 2.7; p<0.0001). In addition, BDNF serum concentrations in FM patients were independent from age, gender, illness duration, preexisting recurrent major depression and antidepressive medication in low doses. In conclusion, the results from our study indicate that BDNF may be involved in the pathophysiology of pain in FM. Nevertheless, how BDNF increases susceptibility to pain is still not known.

Epilepsy in an elderly patient caused by Hashimoto's encephalopathy.

Late-onset seizures are frequently caused by cerebrovascular disease, head trauma, degenerative disorders or CNS tumors. In one-third of cases, the etiology remains obscure. In only 60-70% of adult-onset epilepsy is antiepileptic drug treatment successful. Although seizures are a well-known symptom of Hashimoto's encephalopathy, it is rarely taken into consideration as differential diagnosis in epilepsy. We describe a 74-year-old patient with seizures and slowly progressive cognitive deterioration. Previous therapeutic attempts with carbamazepine, lamotrigine and topiramate had not been effective. We suspected Hashimoto's encephalopathy, which was treated with prednisolone 100 mg/d over 6 months. This regimen led to a cessation of the complex partial seizures and cognitive improvement. We conclude that Hashimoto's encephalopathy is a possible differential diagnosis in epilepsy in the elderly. Glucocorticoid treatment should be considered if there are no important contraindications.

Randomized controlled trial of relapse prevention and a standard behavioral intervention with adult smokers.

A previously evaluated behavioral intervention (SB) was modified to focus on relapse prevention (RP) in order to improve adult smokers' ability to cope with high-risk situations and maintain abstinence. Treatment-seeking smokers (N=79) working at four mid-sized businesses attended either an SB (n=38) or an RP intervention (n=41). Both interventions consisted of 6 and 90-min sessions over 8 weeks and included nicotine replacement therapy. Immediately following the interventions, 42.1% of the SB group and 41.5% of the RP group were abstinent (p=.95). The one-year point-prevalence abstinence rates were 28.9% in the SB group and 17.1% in the RP group (p=.21). As there were no significant group differences on abstinence at follow-up, the RP intervention was not found to be more efficacious than a standard behavioral intervention among treatment-seeking adult smokers. Motivation, on the other hand, was a significant predictor of short- and long-term abstinence.

The German Research Network on Schizophrenia--impact on the management of schizophrenia.

The German Research Network On Schizophrenia (GRNS) is a nationwide network currently comprising 16 psychiatric university departments and 14 state and district hospitals, as well as six local networks of psychiatric practices and general practitioners collaborating on about 25 interrelated, multicenter projects on schizophrenia research. The GRNS aims to intensify collaboration and knowledge exchange between leading research institutions and qualified routine care facilities, both within (horizontal network) and between (vertical network) the two levels of research and care, in order to create the scientific preconditions for optimization of the management of schizophrenia. The concept and the first results of studies aiming at the investigation of (i) strategies for early detection and early intervention in the prodromal stage of psychosis; (ii) treatment in first-episode schizophrenia; (iii) quality management; and (iv) destigmatization, are described as examples of this effort.

Decline of immune responsiveness: a pathogenetic factor in Alzheimer's disease?

The involvement of immunological alterations in the pathogenesis of Alzheimer's disease (AD) is widely discussed. Hitherto, findings on systemic immunological alterations are inconsistent. We measured the concentrations of the pro-inflammatory cytokines IL-1beta, IL-2, IL-6, and TNF-alpha, and of the soluble receptors sIL-2r, sIL-6r, and sTNF-alphar, in cerebrospinal fluid (CSF) and serum of 20 Alzheimer patients and 21 controls. Moreover, we studied levels of the pro-inflammatory IL-6, Il-12, IFN-gamma, and TNF-alpha, and of the anti-inflammatory IL-5 and IL-13 in stimulated blood cell cultures from 27 AD patients and 25 controls. The levels in CSF and serum were diminished in AD or under detection limit. In mitogen-stimulated blood cultures we found a significant decrease of pro- and anti-inflammatory cytokines in the AD group. Our data suggest a general decline of immune responsiveness in AD. Based on the recent research, an impaired immune response may be considered as a pathogenetically relevant factor in AD. With respect to the putative role of ageing in AD, we assume a premature immunosenescence contributing to the Alzheimer's pathology.