MONOCLONAL ANTIBODY THERAPY IN AUTOANTIBODY-ASSOCIATED PSYCHOTIC DISORDERS AND SCHIZOPHRENIA: NARRATIVE REVIEW OF PAST AND CURRENT CLINICAL TRIALS

Neural cell-surface autoantibody-associated psychiatric disease and a subgroup of psychotic disorders are probably caused by an immune dysregulation such as B-cell related autoantibody production. In this review we describe past and current randomized placebo-controlled trials investigating monoclonal antibodies as therapy for autoantibody-associated psychiatric disease and psychotic disorders, aiming to delineate the current landscape of such monoclonal antibodies in autoantibody-associated psychiatric disease and psychotic disorders, as well as perspectives for future trials. Rituximab and ocrelizumab are now being tested in clinical trials, whereas the initial results on tocilizumab are controversial, as they demonstrated a cognitive-function benefit in an open label study in schizophrenic patients – results that were not replicated in a randomized placebo-controlled trial. Adalinumab as TNFalpha blockage was effective in treating positive and negative symptoms in schizophrenia. These findings demonstrate that monoclonal antibody therapy is a potentially promising option to treat subgroups of schizophrenia and autoantibody-associated psychiatric patients, but it should be investigated in more placebo-controlled, double-blind trials with large cohorts

Efficacy and Interindividual Variability in Motor-Cortex Plasticity following Anodal tDCS and Paired-Associative Stimulation

Interindividual response variability to various motor-cortex stimulation protocols has been recently reported. Comparative data of stimulation protocols with different modes of action is lacking. We aimed to compare the efficacy and response variability of two LTP-inducing stimulation protocols in the human motor cortex: anodal transcranial direct current stimulation (a-tDCS) and paired-associative stimulation (PAS25). In two experiments 30 subjects received 1mA a-tDCS and PAS25. Data analysis focused on motor-cortex excitability change and response defined as increase in MEP applying different cut-offs. Furthermore, the predictive pattern of baseline characteristics was explored. Both protocols induced a significant increase in motor-cortical excitability. In the PAS25 experiments the likelihood to develop a MEP response was higher compared to a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for a response was higher in the a-tDCS experiments. Baseline ICF (12 ms) correlated positively with an increase in MEPs only following a-tDCS and responders had significantly higher ICF baseline values. Contrary to recent studies, we showed significant group-level efficacy following both stimulation protocols confirming older studies. However, we also observed a remarkable amount of nonresponders. Our findings highlight the need to define sufficient physiological read-outs for a given plasticity protocol and to develop predictive markers for targeted stimulation

Repositioning synthetic glucocorticoids in psychiatric disease associated with neural autoantibodies: a narrative review

Synthetic glucocorticoids (sGCs) are a well-investigated and standard drug therapy for disorders associated with CNS inflammation. Less is known about treating psychiatric disorders associated with neural autoantibodies. Our aim is to elucidate the repositioning of sGCs in psychiatric diseases that co-exist with neural autoantibodies. We used PubMed to identify articles for this narrative review. To our knowledge, no randomized, placebo-controlled trials have yet been conducted on applying sGC to treat neural autoantibody-associated psychiatric disorders. We describe initial results of cohort studies and single cases or case series often associated with autoantibodies against membrane-surface antigens demonstrating a largely beneficial response to sGCs either as monotherapy or polytherapy together with other immunosuppressive agents. However, sGCs may be less efficient in patients with psychiatric diseases associated with autoantibodies directed against intracellular antigens. These results reveal potential benefits of the novel usage of sGCs for the indication of neural autoantibody-associated psychiatric disease. Further large-scale randomized, placebo-controlled trials are needed to discover whether sGCs are safe, well tolerated, and beneficial in subgroups of neural autoantibody-associated psychiatric diseases

Depression in Somatic Disorders: Is There a Beneficial Effect of Exercise?

Background: The beneficial effects of exercise training on depressive symptoms are well-established. In the past years, more research attention has been drawn to the specific effects of exercise training on depressive symptoms in somatically ill patients. This reviews aims at providing a comprehensive overview of the current findings and evidence of exercise interventions in somatic disorders to improve depressive symptoms. Methods: We systematically searched PubMed and Cochrane databases and extracted meta-analyses from somatically ill patients that underwent exercise interventions and provided information about the outcome of depressive symptoms. Results: Of the 4123 detected publications, 39 were selected for final analysis. Various diseases were included (breast-cancer, prostate cancer, mixed-cancer, cardiovascular disease, coronary heart disease, hemodialysis, fibromyalgia syndrome, acute leukemia, other hematological malignancies, heart failure, HIV, multiple sclerosis, mixed neurological disorders, Parkinson's disease, stroke, ankylosing spondylitis, traumatic brain injury, lupus erythematodes). Most meta-analyses (33/39) found beneficial effects on depressive symptoms, but quality of the included studies as well as duration, intensity, frequency, and type of exercise varied widely. Conclusion: Exercise training has the potential to improve depressive symptoms in patients with somatic disorders. For specific training recommendations, more high quality studies with structured exercise programs and better comparability are needed

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia;neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms;lower levels of global functioning;and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets