Showing papers in "European Archives of Psychiatry and Clinical Neuroscience in 2015"

Risk of dementia in elderly patients with the use of proton pump inhibitors

Abstract: Drugs that modify the risk of dementia in the elderly are of potential interest for dementia prevention. Proton pump inhibitors (PPIs) are widely used to reduce gastric acid production, but information on the risk of dementia is lacking. We assessed association between the use of PPIs and the risk of dementia in elderly people. Data were derived from a longitudinal, multicenter cohort study in elderly primary care patients, the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe), including 3,327 community-dwelling persons aged ≥75 years. From follow-up 1 to follow-up 4 (follow-up interval 18 months), we identified a total of 431 patients with incident any dementia, including 260 patients with Alzheimer’s disease. We used time-dependent Cox regression to estimate hazard ratios of incident any dementia and Alzheimer’s disease. Potential confounders included in the analysis comprised age, sex, education, the Apolipoprotein E4 (ApoE4) allele status, polypharmacy, and the comorbidities depression, diabetes, ischemic heart disease, and stroke. Patients receiving PPI medication had a significantly increased risk of any dementia [Hazard ratio (HR) 1.38, 95 % confidence interval (CI) 1.04–1.83] and Alzheimer’s disease (HR 1.44, 95 % CI 1.01–2.06) compared with nonusers. Due to the major burden of dementia on public health and the lack of curative medication, this finding is of high interest to research on dementia and provides indication for dementia prevention.

Neural circuits of emotion regulation: a comparison of mindfulness-based and cognitive reappraisal strategies.

Abstract: Dealing with one's emotions is a core skill in everyday life. Effective cognitive control strategies have been shown to be neurobiologically represented in prefrontal structures regulating limbic regions. In addition to cognitive strategies, mindfulness-associated methods are increasingly applied in psychotherapy. We compared the neurobiological mechanisms of these two strategies, i.e. cognitive reappraisal and mindfulness, during both the cued expectation and perception of negative and potentially negative emotional pictures. Fifty-three healthy participants were examined with functional magnetic resonance imaging (47 participants included in analysis). Twenty-four subjects applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level, both strategies were associated with comparable activity of the medial prefrontal cortex and the amygdala. When expecting negative versus neutral stimuli, the mindfulness group showed stronger activations in ventro- and dorsolateral prefrontal cortex, supramarginal gyrus as well as in the left insula. During the perception of negative versus neutral stimuli, the two groups only differed in an increased activity in the caudate in the cognitive group. Altogether, both strategies recruited overlapping brain regions known to be involved in emotion regulation. This result suggests that common neural circuits are involved in the emotion regulation by mindfulness-based and cognitive reappraisal strategies. Identifying differential activations being associated with the two strategies in this study might be one step towards a better understanding of differential mechanisms of change underlying frequently used psychotherapeutic interventions.

Neurobiological background of negative symptoms

Abstract: Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords “negative symptoms,” “deficit schizophrenia,” “persistent negative symptoms,” “neurotransmissions,” “neuroimaging” and “genetic.” Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

The German guidelines for the treatment of anxiety disorders.

Abstract: A consensus group consisting of 36 experts representing 20 leading German specialist societies and patient self-help organizations developed evidence-based recommendations for the treatment of anxiety disorders in Germany. These were based on a systematic review of randomized controlled trials on anxiety disorders (n = 403) and on preexisting German and international guidelines. According to the consensus committee, anxiety disorders should be treated with psychotherapy or pharmacological drugs or a combination of both. Cognitive behavioral therapy (CBT) was regarded as the psychological treatment with the highest level of evidence. Psychodynamic therapy (PDT) was recommended for cases in which CBT was not effective or not available or in which PDT was the informed patient’s preferred option. First-line drugs for anxiety disorders include selective serotonin reuptake inhibitors and serotonin–noradrenaline reuptake inhibitors. After remission, medications should be continued for 6–12 months. When either drug or psychotherapy was not effective, treatment should be switched to the other approach or to a combination of both. For patients non-responsive to standard treatments, alternative strategies are suggested. When developing a treatment plan, efficacy, side effects, costs and the preference of the patient should be considered. A large amount of data available from randomized controlled trials permit the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. The recommendations were not only developed for the special situation in Germany, but may also be helpful for developing treatment plans in other countries.

Proteomics of the corpus callosum unravel pivotal players in the dysfunction of cell signaling, structure, and myelination in schizophrenia brains

Abstract: Schizophrenia is an incurable and debilitating mental disorder that may affect up to 1% of the world population. Morphological, electrophysiological, and neurophysiological studies suggest that the corpus callosum (CC), which is the largest portion of white matter in the human brain and responsible for inter-hemispheric communication, is altered in schizophrenia patients. Here, we employed mass spectrometry-based proteomics to investigate the molecular underpinnings of schizophrenia. Brain tissue samples were collected postmortem from nine schizophrenia patients and seven controls at the University of Heidelberg, Germany. Because the CC has a signaling role, we collected cytoplasmic (soluble) proteins and submitted them to nano-liquid chromatography-mass spectrometry (nano LC-MS/MS). Proteomes were quantified by label-free spectral counting. We identified 5678 unique peptides that corresponded to 1636 proteins belonging to 1512 protein families. Of those proteins, 65 differed significantly in expression: 28 were upregulated and 37 downregulated. Our data increased significantly the knowledge derived from an earlier proteomic study of the CC. Among the differentially expressed proteins are those associated with cell growth and maintenance, such as neurofilaments and tubulins; cell communication and signaling, such as 14-3-3 proteins; and oligodendrocyte function, such as myelin basic protein and myelin-oligodendrocyte glycoprotein. Additionally, 30 of the differentially expressed proteins were found previously in other proteomic studies in postmortem brains; this overlap in findings validates the present study and indicates that these proteins may be markers consistently associated with schizophrenia. Our findings increase the understanding of schizophrenia pathophysiology and may serve as a foundation for further treatment strategies.

Decreased quinolinic acid in the hippocampus of depressive patients: evidence for local anti-inflammatory and neuroprotective responses?

Abstract: Disturbances of glutamatergic neurotransmission and mononuclear phagocyte system activation have been described uni- and bipolar depression (UD/BD). Linking the glutamate and immune hypotheses of depression, quinolinic acid (QUIN) is synthesized by activated microglia and acts as an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist with neurotoxic properties. Recently, we observed an increased microglial QUIN expression in the subgenual and supracallosal, but not in the pregenual part of the anterior cingulate cortex in postmortem brains of suicide cases with severe depression. Since several hints point to a role of the hippocampus in depression, we extended our study and addressed the question whether microglial QUIN is also changed in subregions of the hippocampus (CA1 and CA2/3 areas) in these patients. Postmortem brains of 12 acutely depressed patients (UD, n = 6; BD, n = 6) and 10 neuropsychiatric healthy age- and gender-matched control subjects were analyzed using QUIN-immunohistochemistry. Hippocampal volumes were determined in order to assess possible neurotoxic or neurodegenerative aspects. Microglial QUIN expression in the whole group of depressed patients was either comparable (left CA1, right CA2/3) or decreased (right CA1: p = 0.004, left CA2/3: p = 0.044) relative to controls. Post hoc tests showed that QUIN was reduced both in UD and BD in the right CA1 field (UD, p = 0.048; BD, p = 0.031). No loss of hippocampal volume was detected. Our data indicate that UD and BD are associated with a local reduction in QUIN-immunoreactive microglia in the hippocampus and underline the importance of the NMDA-R signaling in depressive disorders.

Reduced volume of the nucleus accumbens in heroin addiction

Abstract: The neural mechanisms of heroin addiction are still incompletely understood, even though modern neuroimaging techniques offer insights into disease-related changes in vivo. While changes on cortical structure have been reported in heroin addiction, evidence from subcortical areas remains underrepresented. Functional imaging studies revealed that the brain reward system and particularly the nucleus accumbens (NAcc) play a pivotal role in the pathophysiology of drug addiction. The aim of this study was to investigate whether there was a volume difference of the NAcc in heroin addiction in comparison to healthy controls. A further aim was to correlate subcortical volumes with clinical measurements on negative affects in addiction. Thirty heroin-dependent patients under maintenance treatment with diacetylmorphine and twenty healthy controls underwent structural MRI scanning at 3T. Subcortical segmentation analysis was performed using FMRIB's Integrated Registration and Segmentation Tool function of FSL. The State-Trait Anxiety Inventory and the Beck Depression Inventory were used to assess trait anxiety and depressive symptoms, respectively. A decreased volume of the left NAcc was observed in heroin-dependent patients compared to healthy controls. Depression score was negatively correlated with left NAcc volume in patients, whereas a positive correlation was found between the daily opioid dose and the volume of the right amygdala. This study indicates that there might be structural differences of the NAcc in heroin-dependent patients in comparison with healthy controls. Furthermore, correlations of subcortical structures with negative emotions and opioid doses might be of future relevance for the investigation of heroin addiction.

Increased power of resting-state gamma oscillations in autism spectrum disorder detected by routine electroencephalography

Abstract: Experimental studies suggest that increased resting-state power of gamma oscillations is associated with autism spectrum disorder (ASD). To extend the clinical applicability of this finding, we retrospectively investigated routine electroencephalography (EEG) recordings of 19 patients with ASD and 19 age- and gender-matched controls. Relative resting-state condition gamma spectral power was variable, but on average significantly increased in children with ASD. This effect remained when excluding electrodes associated with myogenic gamma activity. These findings further indicate that increased resting-state gamma activity characterizes a subset of ASD and may also be detected by routine EEG as a clinically accessible and well-tolerated investigation.

Pharmacological treatment of negative symptoms in schizophrenia

Abstract: Effective treatment of negative symptoms is one of the most important unmet needs in schizophrenic disorders Because the evidence on current psychopharmacological treatments is unclear, the authors reviewed the findings published to date by searching PubMed with the keywords negative symptoms, antipsychotics, antidepressants, glutamatergic compounds, monotherapy and add-on therapy and identifying additional articles in the reference lists of the resulting publications The findings presented here predominantly focus on results of meta-analyses Evidence for efficacy of current psychopharmacological medications is difficult to assess because of methodological problems and inconsistent results In general, the second-generation antipsychotics (SGAs) do not appear to have good efficacy in negative symptoms, although some show better efficacy than first-generation antipsychotics, some of which also demonstrated efficacy in negative symptoms Specific trials on predominant persistent negative symptoms are rare and have been performed with only a few SGAs More often, trials on somewhat persistent negative symptoms evaluate add-on strategies to ongoing antipsychotic treatment Such trials, mostly on modern antidepressants, have demonstrated some efficacy Several trials with small samples have evaluated add-on treatment with glutamatergic compounds, such as the naturally occurring amino acids glycine and d-serine and new pharmacological compounds The results are highly inconsistent, although overall efficacy results appear to be positive The unsatisfactory and inconsistent results can be partially explained by methodological problems These problems need to be solved in the future, and the authors propose some possible solutions Further research is required to identify effective treatment for the negative symptoms of schizophrenia

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

Abstract: Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study

Abstract: Despite many pharmacological and psychosocial treatment options, schizophrenia remains a debilitating disorder. Thus, new treatment strategies rooted in the pathophysiology of the disorder are needed. Recently, vagus nerve stimulation (VNS) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia. The objective of this study was to investigate for the first time the feasibility, safety and efficacy of transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham-controlled, double-blind trial was conducted from 2010 to 2012. Twenty schizophrenia patients were randomly assigned to one of two treatment groups. The first group (active tVNS) received daily active stimulation of the left auricle for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation. Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12. Various other secondary measures were assessed to investigate safety and efficacy. The intervention was well tolerated with no relevant adverse effects. We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period. Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups. Application of tVNS was well tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia, the overall pattern of symptom change might warrant further investigations in this population.

Emotional information processing in depression and burnout: an eye-tracking study

Abstract: Whether burnout is a form of depression is unclear. The aim of this study was to examine the relevance of the burnout-depression distinction by comparing attentional processing of emotional information in burnout and depression. Eye-tracking technology was employed for assessing overt attentional deployment. The gaze of 54 human services employees was monitored as they freely viewed a series of emotional images, labeled as dysphoric, positive, anxiogenic, and neutral. Similar to depression, burnout was associated with increased attention for dysphoric stimuli and decreased attention for positive stimuli. Hierarchical multiple regression analyses revealed that burnout no longer predicted these attentional alterations when depression was controlled for and vice versa, suggesting interchangeability of the two entities in this matter. To our knowledge, this study is the first to (a) investigate emotional attention in burnout and (b) address the issue of the burnout-depression overlap at both cognitive and behavioral levels using eye movement measurement. Overall, our findings point to structural similarities between burnout and depression, thus deepening concerns regarding the singularity of the burnout phenomenon.

Aberrant NMDA receptor DNA methylation detected by epigenome-wide analysis of hippocampus and prefrontal cortex in major depression

Abstract: Current perspectives on the molecular underpinnings of major depressive disorder (MDD) posit a mechanistic role of epigenetic DNA modifications in mediating the interaction between environmental risk factors and a genetic predisposition. However, conclusive evidence for differential methylation signatures in the brain’s epigenome of MDD patients as compared to controls is still lacking. To address this issue, we conducted a pilot study including an epigenome-wide methylation analysis in six individuals diagnosed with recurrent MDD and six control subjects matched for age and gender, with a priori focus on the hippocampus and prefrontal cortex as pathophysiologically relevant candidate regions. Our analysis revealed differential methylation profiles of 11 genes in hippocampus and 20 genes in prefrontal cortex, five of which were selected for replication of the methylation status using pyrosequencing. Among these replicated targets, GRIN2A was found to be hypermethylated in both prefrontal cortex and hippocampus. This finding may be of particular functional relevance as GRIN2A encodes the glutamatergic N-methyl-d-aspartate receptor subunit epsilon-1 (NR2A) and is known to be involved in a plethora of synaptic plasticity-related regulatory processes probably disturbed in MDD.

Stigmatization of psychiatrists and general practitioners: results of an international survey.

Abstract: The stigma of mental illness affects psychiatry as a medical profession and psychiatrists. The present study aimed to compare the extent and correlation patterns of perceived stigma in psychiatrists and general practitioners. An international multicenter survey was conducted in psychiatrists and general practitioners from twelve countries. Responses were received from N = 1,893 psychiatrists and N = 1,238 general practitioners. Aspects of stigma assessed in the questionnaire included perceived stigma, self-stigma (stereotype agreement), attitudes toward the other profession, and experiences of discrimination. Psychiatrists reported significantly higher perceived stigma and discrimination experiences than general practitioners. Separate multiple regression analyses showed different predictor patterns of perceived stigma in the two groups. Hence, in the psychiatrists group, perceived stigma correlated best with discrimination experiences and self-stigma, while in the general practitioners group it correlated best with self-stigma. About 17 % of the psychiatrists perceive stigma as a serious problem, with a higher rate in younger respondents. Against this background, psychiatry as a medical profession should set a high priority on improving the training of young graduates. Despite the number of existing antistigma interventions targeting mental health professionals and medical students, further measures to improve the image of psychiatry and psychiatrists are warranted, in particular improving the training of young graduates with respect to raising awareness of own stigmatizing attitudes and to develop a better profession-related self-assertiveness.

Psychometric evaluation of the negative syndrome of schizophrenia.

Abstract: In this paper, we reviewed the available instruments for assessing the negative syndrome of schizophrenia, describing their strengths and weaknesses. Current instruments were classified into two categories according to their content validity and assessment approach as first- or second-generation instruments. The BPRS, SANS, the SENS and the PANSS belong to the first generation, while the BNSS, the CAINS and the MAP-SR belong to the second generation. The NSA can be considered a transitional instrument between the two. First-generation instruments have more content validity problems than second-generation instruments do, as they do not accurately reflect the currently accepted negative syndrome (they do not include all negative symptoms and signs or they include symptoms from other dimensions). They also have more problems relative to the use of behavioural referents instead of internal experiences of deficits when assessing symptoms, which may lead to measuring functioning instead of negative symptoms. Further research needs to be done in this area in order to ensure the evaluation of primary negative symptoms and internal experiences involved in negative symptoms rather than external behaviours.

Predictors of burnout: results from a prospective community study

Abstract: The possible link between work strain and subsequent mental disorders has attracted public attention in many European countries. Burnout has become a favored concept within this context. Most burnout research has concentrated on various professional groups and less so on ordinary community samples. We analyzed the data collected from a 30-year community sample during seven measuring occasions, beginning in 1978. In the last assessment (2008), we included for the first time the Maslach Burnout Inventory (MBI). Making the diagnosis of a lifetime mental disorder a predictor for burnout required us to compile the cumulative prevalence rate over all seven occasions. We also evaluated various psycho-social predictors of burnout over the life cycle of our sample. Concurrent associations of the MBI with subscales from the SCL-90-R were also investigated. The relationship of burnout with several SCL-90-R subscales demonstrated that, in all dimensions, burnout is associated with significant psychopathology. Persons with a lifetime mood disorder, and especially those with a combination of mood and anxiety disorders, had a higher risk for subsequent burnout. Various partnership problems were another predictor for burnout. In conclusion, the role of mental disorder as an occupational illness remains controversial. Various forms of such disorders as well as some psycho-social predictors can predispose to burnout. By contrast, work-related predictors appear to be less important.

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: a multi-centre study

Abstract: The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses.

Considering the base rates of low performance in cognitively healthy older adults improves the accuracy to identify neurocognitive impairment with the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB).

Abstract: It is common for some healthy older adults to obtain low test scores when a battery of neuropsychological tests is administered, which increases the risk of the clinician misdiagnosing cognitive impairment. Thus, base rates of healthy individuals’ low scores are required to more accurately interpret neuropsychological results. At present, this information is not available for the German version of the Consortium to Establish a Registry for Alzheimer’s Disease-Neuropsychological Assessment Battery (CERAD-NAB), a frequently used battery in the USA and in German-speaking Europe. This study aimed to determine the base rates of low scores for the CERAD-NAB and to tabulate a summary figure of cut-off scores and numbers of low scores to aid in clinical decision making. The base rates of low scores on the ten German CERAD-NAB subscores were calculated from the German CERAD-NAB normative sample (N = 1,081) using six different cut-off scores (i.e., 1st, 2.5th, 7th, 10th, 16th, and 25th percentile). Results indicate that high percentages of one or more “abnormal” scores were obtained, irrespective of the cut-off criterion. For example, 60.6 % of the normative sample obtained one or more scores at or below the 10th percentile. These findings illustrate the importance of considering the prevalence of low scores in healthy individuals. The summary figure of CERAD-NAB base rates is an important supplement for test interpretation and can be used to improve the diagnostic accuracy of neurocognitive disorders.

Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis

Abstract: We performed an updated meta-analysis of randomized double-blind placebo-controlled trials (RCTs) on the effects of varenicline adjuvant therapy for smoking cessation in people with schizophrenia, on the basis of a previous meta-analysis (Tsoi in Cochrane Database Syst Rev 2:CD007253, 2013). We searched PubMed, the Cochrane Library databases, and PsycINFO up to August 1, 2014. RCTs comparing varenicline adjuvant therapy with placebo in schizophrenia were included. The risk ratio (RR), number needed to harm (NNH), and standardized mean differences with its 95 % confidence interval (CI) were used. Seven studies (total n = 439), including 6 with only schizophrenia (total n = 352), 1 with both schizophrenia (n = 77) and bipolar disorder (n = 10), were included. Varenicline was not superior to placebo in smoking cessation (RR = 0.79, 95 % CI 0.58–1.08, p = 0.14, 5 RCTs, n = 322). Varenicline failed to show its superiority to placebo for overall, positive, negative, and depressive symptoms. Moreover, there was no significant difference in the discontinuation rate due to all causes, clinical deterioration, or side effects between varenicline and placebo. Although varenicline caused less abnormal dreams/nightmares than placebo (RR = 0.47, 95 % CI 0.22–0.99, p = 0.05, NNH = not significant, 4 RCTs, n = 288), it caused more nausea (RR = 1.79, 95 % CI 1.20–2.67, p = 0.004, NNH = 6, p = 0.004, 6 RCTs, n = 417). We detected no significant difference in suicidal ideation and depression between varenicline and placebo. Our results suggest that although varenicline adjuvant therapy is well tolerated, varenicline is not superior to placebo for smoking cessation in people with schizophrenia. Because of the limited sample sizes of the available studies, future studies will require larger samples to ensure that these findings are generalizable.

Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF as diagnostic biomarkers for major depressive disorder and bipolar disorder.

Abstract: signal peptide, proBDNF (~32 kDa) is converted to mature BDNF by extracellular proteases. It was initially thought that only secreted, mature BDNF was biologically active, and that proBDNF, which localizes intracellularly, served as an inactive precursor. However, accumulating evidence shows that both proBDNF and mature BDNF are active, eliciting opposing effects via the p75 and TrkB receptors, respectively, and that both forms are important in several physiological functions [2–6]. In 2003, we reported that serum levels of BDNF in drug-naive patients with MDD were significantly lower than those of healthy controls and that serum BDNF levels increased after antidepressant treatment [7]. A recent metaanalysis of 179 associations (N = 9,484 subjects) showed that serum levels of total BDNF (mature BDNF and proBDNF) in antidepressant-free patients with MDD were significantly (Cohen’s d = −0.71, p < 0.0000001) lower than those of healthy controls [8], supporting our previous report [7]. The BDNF enzyme-linked immunosorbent assay (ELISA) kits, used in the previous reports, recognized both proBDNF and mature BDNF, due to the limited specificity of this particular BDNF antibody [9]. Using new commercially available human BDNF ELISA kits which differentiate between proBDNF and mature BDNF, we reported high concentrations of both proBDNF and mature BDNF in human serum [9]. Subsequently, we reported that in medicated patients with MDD, serum levels of mature BDNF, but not proBDNF, were significantly lower than those of healthy controls [10]. In contrast, we recently reported that serum levels of mature BDNF and the ratio of mature BDNF to proBDNF in mood-stabilized BD patients were significantly higher than in healthy controls [11]. Interestingly, serum levels of proBDNF in mood-stabilized patients with BD were significantly lower than those in healthy controls [11]. These findings in BD were confirmed in two Letter to the editors

Unipolar mania: a necessary diagnostic concept.

Abstract: In the classification of mood disorders, major depressive disorder is separate from bipolar disorders whereas mania is not. Studies on pure mania are therefore rare. Our paper reviews the evidence for distinguishing pure mania (M) and mania with mild depression (Md) from bipolar disorder. Two large epidemiological studies found a prevalence of 1.7–1.8 % of M/Md in adolescents and adults. Several clinical follow-up studies demonstrated good stability of the diagnosis after a previous history of three manic episodes. Compared to bipolar disorder, manic disorder is characterised by a weaker family history for depression, an earlier onset, fewer recurrences and better remission, and is less comorbid with anxiety disorders. In addition, mania is strongly associated with a hyperthymic temperament, manifests more psychotic symptoms and is more often treated with antipsychotics. Twin and family studies find mania to be more heritable than depression and show no significant transmission from depression to mania or from mania to depression. Cardiovascular mortality is elevated among patients with mood disorders generally and is highest among those with mania. In non-Western countries, mania and the manic episodes in bipolar disorder are reported to occur more frequently than in Western countries.

Retinal dysfunction of contrast processing in major depression also apparent in cortical activity

Abstract: Depressive disorder is often associated with the subjective experience of altered visual perception. Recent research has produced growing evidence for involvement of the visual system in the pathophysiology of depressive disorder. Using the pattern electroretinogram (PERG), we found reduced retinal contrast response in patients with major depression. Based on this observation, the question arises whether this change has a cortical correlate. To evaluate this, we analyzed the visual evoked potential (VEP) of the occipital cortex in 40 patients with depressive disorder and 28 healthy controls. As visual stimuli, checkerboard stimuli of 0.51° check size, 12.5 reversals per second and a contrast of 3–80 % was used. In addition to the PERG, we recorded the VEP with an Oz versus FPz derivation. The amplitude versus contrast transfer function was compared across the two groups and correlated with the severity of depression, as measured by the Hamilton Depression Rating Scale and the Beck Depression Inventory. Patients with major depression displayed significantly reduced VEP amplitudes at all contrast levels compared to control subjects (p = 0.029). The VEP amplitude correlated with psychometric measures for severity of depression. The degree of depression reduced the contrast transfer function in the VEP to a lesser extent than in the PERG: While the PERG is reduced to ≈50 %, the VEP is reduced to 75 %. Our results suggest that depression affects the cortical response in major depression, but less so than the retinal responses. Modified contrast adaptation in the lateral geniculate nucleus or cortex possibly moderates the increased losses in the retina.

Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients.

Abstract: Thyroid diseases are often associated with psychiatric disorders The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 % A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed The proportion of pathologically increased anti-TPO levels in patients with depression was high Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (χ (2) = 55; p = 0019) different between patients with depression (327 %) and patients with schizophrenia (53 %) In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 12-853) when compared with schizophrenia patients TSH basal level did not differ between patients with depression and patients with schizophrenia Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity

Visual height intolerance and acrophobia: clinical characteristics and comorbidity patterns

Abstract: The purpose of this study was to estimate the general population lifetime and point prevalence of visual height intolerance and acrophobia, to define their clinical characteristics, and to determine their anxious and depressive comorbidities. A case–control study was conducted within a German population-based cross-sectional telephone survey. A representative sample of 2,012 individuals aged 14 and above was selected. Defined neurological conditions (migraine, Meniere’s disease, motion sickness), symptom pattern, age of first manifestation, precipitating height stimuli, course of illness, psychosocial impairment, and comorbidity patterns (anxiety conditions, depressive disorders according to DSM-IV-TR) for vHI and acrophobia were assessed. The lifetime prevalence of vHI was 28.5 % (women 32.4 %, men 24.5 %). Initial attacks occurred predominantly (36 %) in the second decade. A rapid generalization to other height stimuli and a chronic course of illness with at least moderate impairment were observed. A total of 22.5 % of individuals with vHI experienced the intensity of panic attacks. The lifetime prevalence of acrophobia was 6.4 % (women 8.6 %, men 4.1 %), and point prevalence was 2.0 % (women 2.8 %; men 1.1 %). VHI and even more acrophobia were associated with high rates of comorbid anxious and depressive conditions. Migraine was both a significant predictor of later acrophobia and a significant consequence of previous acrophobia. VHI affects nearly a third of the general population; in more than 20 % of these persons, vHI occasionally develops into panic attacks and in 6.4 %, it escalates to acrophobia. Symptoms and degree of social impairment form a continuum of mild to seriously distressing conditions in susceptible subjects.

Inhibition of MAPK/ERK signaling blocks hippocampal neurogenesis and impairs cognitive performance in prenatally infected neonatal rats

Abstract: Hippocampus endogenous neurogenesis has been postulated to play a favorable role in brain restoration after injury. However, the underlying molecular mechanisms have been insufficiently deciphered. Here we investigated the potential regulatory capacity of MAPK/ERK signaling on neurogenesis and the associated cognitive performance in prenatally infected neonatal rats. From our data, intrauterine infection could induce hippocampal neuronal apoptosis and promote endogenous repair by evoking neural stem cell proliferation and survival. We also found intrauterine infection could induce increased levels of p-ERK, p-CREB and BDNF, which might be responsible for the potential endogenous rescue system. Furthermore, inhibition of MAPK/ERK signaling could aggravate hippocampal neuronal apoptosis, decrease neurogenesis, and impair the offspring's cognitive performances and could also down-regulate the levels of p-ERK, p-CREB and BDNF. Our data strongly suggest that the activation of MAPK/ERK signaling may play a significant role in promoting survival of newly generated neural stem cells via an anti-apoptotic mechanism, which may be particularly important in endogenous neuroprotection associated with cognitive performance development in prenatally infected rats.

Stress is a bad advisor. Stress primes poor decision making in deluded psychotic patients

Abstract: Stress is implicated in the onset of psychosis but the complex links between stress and psychotic breakdown are yet poorly understood. For the present study, we examined whether two prominent cognitive biases in psychosis, jumping to conclusions and distorted attribution, in conjunction with neuropsychological deficits play a role in this process. Thirty participants with schizophrenia and acute delusional symptoms were compared with 29 healthy controls across three conditions involving a noise stressor, a social stressor or no stressor. Under each condition participants had to perform parallel versions of cognitive bias tasks and neuropsychological tests including a probabilistic reasoning task (jumping to conclusions), the revised Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R; attributional style), and the Corsi block-tapping task (nonverbal memory). Stress, particularly noise, aggravated performance differences of patients relative to controls on memory. Participants with psychosis demonstrated an escalated jumping to conclusion bias under stress. At a medium effect size, patients made more monocausal attributions, which increased under social stress. The present study is partially in line with prior studies. It suggests that stress negatively affects cognition in psychosis more than in controls, which is presumably insufficiently realized by patients and thus not held in check by greater response hesitance. Raising patients' awareness about these response tendencies and encouraging them to be more cautious in their judgments under conditions of increased stress may prove beneficial for improving positive symptoms.

Decreased entropy modulation of EEG response to novelty and relevance in schizophrenia during a P300 task

Abstract: The analysis of the interaction between novelty and relevance may be of interest to test the aberrant salience hypothesis of schizophrenia (SCH). In comparison with other neuroimaging techniques, such as functional magnetic resonance imaging, electroencephalography (EEG) provides high temporal resolution. Therefore, EEG is useful to analyze transient dynamics in neural activity, even in the range of milliseconds. In this study, EEG activity from 31 patients with SCH and 38 controls was analyzed using Shannon spectral entropy (SE) and median frequency (MF). The aim of the study was to quantify differences between distractor (i.e., novelty) and target (i.e., novelty and relevance) tones in an auditory oddball paradigm. Healthy controls displayed a larger SE decrease in response to target stimulus than in response to distractor tones. SE decrease was accompanied by a significant and widespread reduction of MF (i.e., a significant slowing of EEG activity). In comparison with controls, patients showed a significant reduction of changes in SE in response to both target and distractor tones. These differences were also observed in patients that only received a minimal treatment prior to EEG recording. Furthermore, significant changes in SE were inversely correlated to positive and total symptoms severity for SCH patients. Our findings support the notion that SCH is associated with a reduced response to both novelty and relevance during an auditory P300 task.

S3 guideline on psychosocial therapies in severe mental illness: evidence and recommendations

Abstract: The burden of severe and persistent mental illness is high. Beside somatic treatment and psychotherapeutic interventions, treatment options for patients with severe mental illness also include psychosocial interventions. This paper summarizes the results of a number of systematic literature searches on psychosocial interventions for people with severe mental illness. Based on this evidence appraisal, recommendations for the treatment of people with severe mental illness were formulated and published in the evidence-based guideline series of the German Society for Psychiatry, Psychotherapy and Neurology (DGPPN) as an evidence-based consensus guideline ("S3 guideline"). Recommendations were strongly based on study results, but used consensus processes to consider external validity and transferability of the recommended practices to the German mental healthcare system. A distinction is made between system-level interventions (multidisciplinary team-based psychiatric community care, case management, vocational rehabilitation and participation in work life and residential care interventions) and single psychosocial interventions (psychoeducation, social skills training, arts therapies, occupational therapy and exercise therapy). There is good evidence for the efficacy of the majority of psychosocial interventions in the target group. The best available evidence exists for multidisciplinary team-based psychiatric community care, family psychoeducation, social skills training and supported employment. The present guideline offers an important opportunity to further improve health services for people with severe mental illness in Germany. Moreover, the guideline highlights areas for further research.

Disturbed cortico-amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder

Abstract: Patients suffering from bipolar affective disorder show deficits in working memory functions. In a previous functional magnetic resonance imaging study, we observed an abnormal hyperactivity of the amygdala in bipolar patients during articulatory rehearsal in verbal working memory. In the present study, we investigated the dynamic neurofunctional interactions between the right amygdala and the brain systems that underlie verbal working memory in both bipolar patients and healthy controls. In total, 18 euthymic bipolar patients and 18 healthy controls performed a modified version of the Sternberg item-recognition (working memory) task. We used the psychophysiological interaction approach in order to assess functional connectivity between the right amygdala and the brain regions involved in verbal working memory. In healthy subjects, we found significant negative functional interactions between the right amygdala and multiple cortical brain areas involved in verbal working memory. In comparison with the healthy control subjects, bipolar patients exhibited significantly reduced functional interactions of the right amygdala particularly with the right-hemispheric, i.e., ipsilateral, cortical regions supporting verbal working memory. Together with our previous finding of amygdala hyperactivity in bipolar patients during verbal rehearsal, the present results suggest that a disturbed right-hemispheric “cognitive–emotional” interaction between the amygdala and cortical brain regions underlying working memory may be responsible for amygdala hyperactivation and affects verbal working memory (deficits) in bipolar patients.

Gently restless: association of ADHD-like traits with response inhibition and interference control

Abstract: Impairment of inhibition-related functions is one of the most pronounced cognitive deficits found in attention-deficit/hyperactivity disorder (ADHD). Compelling evidence from studies of unaffected relatives of patients with ADHD and of ADHD-like traits in healthy subjects suggest the continuous distribution of ADHD symptoms in the population. A more subtle inhibitory deficit can also be found in healthy relatives of patients and in subjects with high ADHD-like traits. Here, we examined the relationship between inhibitory performance and ADHD-like traits, for the first time, in a large sample of healthy adults by applying multiple, widely used tests of inhibition-related functions. ADHD-like traits, in general, were independently predicted by Stroop interference score and, at trend level, by go/no-go commission error rate while controlling for socio-demographic factors, verbal intelligence and neuroticism. Additionally, higher inattentive traits were related to worse Stroop performance at trend level, and higher hyperactive/impulsive traits were significantly associated with more go/no-go commission errors. ADHD-like traits were strongly related to neuroticism. The study shows that individual differences in ADHD-like traits are related to variance in fundamental inhibition-related functions over and above effects of negative affect regulation, but the relationships tend to be small. The results suggest the quasi-dimensionality of ADHD and raise further questions about the relationship between genetic factors and the deficit of inhibition-related functions in the ADHD spectrum.