The neoliberal leaning of the neuroscience discourse when it deals with mental health and learning disorders.

Neuroscience attracted increasing attention in mass media during the last decades. Indeed, neuroscience advances raise high expectations in society concerning major societal issues such as mental health and learning difficulties. Unfortunately, according to leading experts, neuroscience advances have not yet benefited patients, students and socially deprived families. Yet, neuroscience findings are widely overstated and misrepresented in the media. Academic studies, briefly described here, showed that most data misrepresentations were already present in the neuroscience literature before spreading in mass media. This triumphalist neuroscience discourse reinforces a neuro-essentialist conception of mental disorders and of learning difficulties. By emphasizing brain plasticity, this discourse fuels the neoliberal ethics that overvalue autonomy, rationality, flexibility and individual responsibility. According to this unrealistic rhetoric, neuroscience-based techniques will soon bring inexpensive private solutions to enduring social problems. When considering the social consequences of this rhetoric, neuroscientists should refrain from overstating the interpretation of their observations in their scientific publications and in their exchanges with journalists.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

45 years German Society of Biological Psychiatry (DGBP).

The foundation of a German Society of Biological Psychiatry (DGBP) was initiated at the Second World Congress of Biological Psychiatry of the WFSBP in Barcelona in 1978. Its mission was and is to promote interdisciplinary research on the biology of mental disorders and to translate results of biological research into clinical practice. During the presidency of Peter Falkai, its tasks were defined to improve the quality and support of biologically oriented research in Germany by the DFG (Deutsche Forschungsgemeinschaft; German Research Foundation), BMBF (Bundesministerium für Bildung und Forschung) and EU (European Union), to promote young researchers doing biologically oriented research, to improve on the diagnosis and therapy of mental disorders and to advise policy makers by taking part in legal processes. The DGBP has been a corporate member of the WFSBP from its beginning, became a cooperative member of the DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde), later of the German Brain Council, and fostered relationships with other scientific societies. Over the past 45 years, more than twenty congresses were held in Germany and neighboring countries. Emerging from the pandemic, the DGBP is ready to continue its mission to promote interdisciplinary research on the biology of mental disorders with a focus on the development of young scientists and to translate results of biological research into clinical practice, with regard to pharmacotherapy in close cooperation with the Arbeitsgemeinschaft Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). In this sense, this article also aims to stimulate the cooperation of the society with other national and international partners and to foster new relationships with young scientists and professionals interested in the aims and goals of the DGBP.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Development of a suspicion index for secondary schizophrenia using the Delphi method.

AIM: The aim of this study was to develop a suspicion index that aids diagnosis of secondary schizophrenia spectrum disorders in regular clinical practice. METHOD: We used the Delphi method to rate and refine questionnaire items in consecutive rounds. Differences in mean expert responses for schizophrenia spectrum disorders and secondary schizophrenia spectrum disorders populations allowed to define low/middle/high predictive items, which received different weights. Algorithm performance was tested in 198 disease profiles by means of sensitivity and specificity. RESULTS: Twelve experts completed the Delphi process, and consensus was reached in 19/24 (79.2%) items for schizophrenia spectrum disorders and 17/24 (70.8%) for secondary schizophrenia spectrum disorders. We assigned rounded values to each item category according to their predictive potential. A differential distribution of scores was observed between schizophrenia spectrum disorders and secondary schizophrenia spectrum disorders when applying the suspicion index for validation to 198 disease profiles. Sensitivity and specificity analyses allowed to set a >8/10/16 risk prediction score as a threshold to consider medium/high/very high suspicion of secondary schizophrenia spectrum disorders. CONCLUSION: Our final outcome was the Secondary Schizophrenia Suspicion Index, the first paper-based and reliable algorithm to discriminate secondary schizophrenia spectrum disorders from schizophrenia spectrum disorders with the potential to help improve the detection of secondary schizophrenia spectrum disorder cases in clinical practice.

Medical Student Attitudes and Perceptions on the Relevance of Neuroscience to Psychiatry: a Mixed Methods Study.

OBJECTIVE: Many psychiatry residency programs are actively incorporating neuroscience training into their curricula; however, relatively little scholarship exploring neuroscience and psychiatry integration in undergraduate medical education has been conducted. This study investigated second-year, pre-clerkship medical students' perceptions on the relationship between neuroscience and psychiatry following foundational neuroscience and behavior instruction to identify their views before they enter clerkships. METHODS: A mixed methods design combined qualitative analysis of medical students' essays in response to the prompt: "What is the relationship between neuroscience and psychiatry?" with quantitative analysis of survey responses on a 7-point scale. RESULTS: Ninety-three percent of the class participated in the study (n = 77). Learners rated neuroscience as important for understanding and treating psychiatric disorders, albeit less important for psychiatric compared to neurological disorders. Using applied thematic analysis, the authors identified qualitative themes. Specifically, participants recognized neuroscience as a foundational science for psychiatry, but some emphasized that factors other than neuroscience are needed to explain psychiatric disorders. Some students perceived neuroscience and psychiatry as complementary approaches to understanding the brain and behavior. Others identified a role for neuroscience in reducing the stigma of psychiatric disorders and thereby improving access to psychiatric care. CONCLUSIONS: The quantitative and qualitative findings reinforced each other and provided novel insight to pre-clerkship medical students' views on the relevance of neuroscience for psychiatry. Educating all medical students, not just psychiatry residents, on the neuroscience of psychiatric disorders may better equip the next generation of physicians, regardless of specialty, to care for their patients with psychiatric conditions.

Kraepelin's psychiatry in the pragmatic age.

The movement of a pendulum is often used as a metaphor to represent the history of twentieth century American psychiatry. On this view, American psychiatry evolved by swinging back and forth between two schools of thought in constant competition: somatic accounts of mental illness and psychodynamic ones. I argue that this narrative partly misrepresents the actual development of American psychiatry. I suggest that there were some important exchanges of ideas and practices in the transition from German biological approaches to American psychodynamic approaches. In particular, two kinds of pragmatism played an important role in this transition: Kraepelin's methodological pragmatism, and pragmatic values present in the American psychiatric context, due in part to the influence of William James. From a historical standpoint, I suggest that the metaphor of the pendulum doesn't capture the full complexities of this shift in psychiatry at the turn of the century; from a philosophical standpoint, my discussion brings to light two strands of pragmatism salient to scientific psychiatry.

Plasma redox and inflammatory patterns during major depressive episodes: a cross-sectional investigation in elderly patients with mood disorders.

BACKGROUND: While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. METHODS: The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). RESULTS: DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. CONCLUSION: Specific alterations of redox systems are detectable among elderly DP.

A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961-76.

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.

The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale : que Devrions-Nous dire à nos Patients?

The gut microbiome as a potential therapeutic target for mental illness is a hot topic in psychiatry. Trillions of bacteria reside in the human gut and have been shown to play a crucial role in gut-brain communication through an influence on neural, immune, and endocrine pathways. Patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia, and autism spectrum disorder have been shown to have significant differences in the composition of their gut microbiome. Enhancing beneficial bacteria in the gut, for example, through the use of probiotics, prebiotics, or dietary change, has the potential to improve mood and reduce anxiety in both healthy people and patient groups. Much attention is being given to this subject in the general media, and patients are becoming increasingly interested in the potential to treat mental illness with microbiome-based therapies. It is imperative that those working with people with mental illness are aware of the rationale and current evidence base for such treatment strategies. In this review, we provide an overview of the gut microbiome, what it is, and what it does in relation to gut-brain communication and psychological function. We describe the fundamental principles and basic techniques used in microbiome-gut-brain axis research in an accessible way for a clinician audience. We summarize the current evidence in relation to microbiome-based strategies for various psychiatric disorders and provide some practical advice that can be given to patients seeking to try a probiotic for mental health benefit.

Association between polymorphisms of NOS1, NOS2 and NOS3 genes and suicide behavior: a systematic review and meta-analysis.

The enzyme nitric oxide synthase has been associated with suicide behavior. NOS1, NOS2 and NOS3 genes are implicated in the production of nitric oxide. However, the association between NOS genes and suicide behavior has not yet been established. To assess the association of Nitric Oxide Synthase (NOS) genes and suicide behavior we performed a systematic review a meta-analysis. We searched articles published in three electronic databases, PubMed, Scopus and Web of Sciences, up to February 2019. We used keywords and combinations "NOS", "NOS1", "NOS2", "NOS3" and "suicide". Only articles that met the inclusion criteria were included. To assess the association between NOS genes and suicide behavior we used allelic, dominant and recessive models, as well as homozygous and heterozygous comparisons. The pooled results showed that rs2682826 of Nitric Oxide Synthase 1 gene (NOS1) increased the risk for suicide attempt in the allelic (OR: 1.34; 95 CI: 1.00-1.78), recessive (OR: 1.45; 95 CI:1.06-1.98) and heterozygous (OR: 1.41; 95 CI: 1.09-1.81) models. We found that the rs2682826 of NOS1 could increase the risk for suicide attempt. However, these results should only be taken as exploratory; more studies are necessary to determine the association between NOS genes and suicide behavior.

How amytal changed psychopharmacy: off-label uses of sodium amytal (1920-40).

In the early 1930s, American neurologist and psychiatrist William Bleckwenn used sodium amytal to render catatonic patients responsive, so that he could engage in talk therapy. Bleckwenn found a new, 'off-label' use for this anaesthetic and anxiolytic medication in psychiatry and, in doing so, allowed for important discoveries in the diagnosis and treatment of catatonia. Pharmacological textbooks reveal a 'label', while the Index-Catalogue of the Library of the Surgeon-General's Office reveals explorations 'off label' of barbiturates. The 'off-label' use of barbiturates facilitated talk therapy, heralding an important shift in psychopharmacy. Drugs previously only used as chemical restraints became a form of treatment for specific psychiatric diseases. The current strictures against off-label prescribing are overprescriptive and close off innovative new uses.

Epigenetics applied to psychiatry: Clinical opportunities and future challenges.

Psychiatric disorders are clinically heterogeneous and debilitating chronic diseases resulting from a complex interplay between gene variants and environmental factors. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly. Given that epigenetic modifications are sensitive to environment, stable, and reversible, epigenetic studies in psychiatry could represent a promising approach to better understanding and treating disease. In the present review, we aim to discuss the clinical opportunities and challenges arising from the epigenetic research in psychiatry. Using selected examples, we first recapitulate key findings supporting the role of adverse life events, alone or in combination with genetic risk, in epigenetic programming of neuropsychiatric systems. Epigenetic studies further report encouraging findings about the use of methylation changes as diagnostic markers of disease phenotype and predictive tools of progression and response to treatment. Then we discuss the potential of using targeted epigenetic pharmacotherapy, combined with psychosocial interventions, for future personalized medicine for patients. Finally, we review the methodological limitations that could hinder interpretation of epigenetic data in psychiatry. They mainly arise from heterogeneity at the individual and tissue level and require future strategies in order to reinforce the biological relevance of epigenetic data and its translational use in psychiatry. Overall, we suggest that epigenetics could provide new insights into a more comprehensive interpretation of mental illness and might eventually improve the nosology, treatment, and prevention of psychiatric disorders.

Recent developments in the genetics of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a developmental psychiatric disorder that affects children and adults. ADHD is one of the psychiatric disorders with the strongest genetic basis according to familial, twin, and single nucleotide polymorphisms (SNP)-based epidemiological studies. In this review, we provide an update of recent insights into the genetic basis of ADHD. We discuss recent progress from genome-wide association studies (GWAS) looking at common variants as well as rare copy number variations. New analysis of gene groups, so-called functional ontologies, provide some insight into the gene networks afflicted, pointing to the role of neurodevelopmentally expressed gene networks. Bioinformatic methods, such as functional enrichment analysis and protein-protein network analysis, are used to highlight biological processes of likely relevance to the etiology of ADHD. Additionally, copy number variations seem to map on important pathways implicated in synaptic signaling and neurodevelopment. While some candidate gene associations of, for example, neurotransmitter receptors and signaling, have been replicated, they do not seem to explain significant variance in recent GWAS. We discuss insights from recent case-control SNP-GWAS that have presented the first whole-genome significant SNP in ADHD.

Stanley Cobb, the Rockefeller Foundation and the evolution of American psychiatry.

Stanley Cobb founded the Harvard Departments of Neurology (1925) and Psychiatry (1934) with Rockefeller Foundation funding. Cobb was an important transitional figure in both neurology and psychiatry. He and his friend Alan Gregg were the most visible parts of the Rockefeller Foundation psychiatry project, which prepared American psychiatry for the rapid growth of psychiatric research after World War II. Edward Shorter called him the founder of American biological psychiatry, but this misunderstands Cobb and the Hegelian evolution of twentieth-century American psychiatry. I review the major role of the Rockefeller Foundation in the evolution of American academic psychiatry and the disappearance of Cobb's teaching and that of his mentor Adolf Meyer, a founding father of American academic psychiatry.

[Research domain criteria (RDoC) : Psychiatric research as applied cognitive neuroscience]. / Research Domain Criteria (RDoC) : Psychiatrische Forschung als angewandte kognitive Neurowissenschaft.

BACKGROUND: Just before the official launch of the DSM-5 in 2013, the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health was made public and is becoming increasingly more important in psychiatric research. OBJECTIVE: The aim of this paper is to clarify the conceptual approach of RDoC, to systematically discuss limitations, to present exemplary RDoC-based studies and to consider the relevance of the RDoC concepts for clinicians and scientists. MATERIAL AND METHODS: The is a qualitative introduction and review article with a critical discussion. RESULTS AND DISCUSSION: The RDoC initiative was not conceived as an alternative diagnostic manual to DSM-5 or IDC-10/11 for use in clinical practice. It is a new systematic framework for psychiatric research based on the most recent results of cognitive neuroscience and aims to map mental disorders dimensionally and transdiagnostically. Despite some weaknesses, it is currently the most elaborated and scientifically grounded approach for multidisciplinary research on mental disorders. In contrast to the purely symptom-based DSM and ICD approaches, which are agnostic with respect to the pathogenesis of mental diseases, the explicit aim of the RDoC initiative is to systematize biological knowledge about risk factors and causes of mental disorders; therefore, it has a much greater potential to develop new and individualized therapeutic strategies based on disease mechanisms.

[Social psychiatry and neurobiology : A long overdue convergence exemplified by schizophrenia]. / Sozialpsychiatrie und Neurobiologie : Eine längst fällige Annäherung am Beispiel der Schizophrenie.

BACKGROUND: The proliferation of biological psychiatry has greatly increased over the last two decades. With the possibility to carry out brain research using modern technical methods, it seemed that social influencing factors would lose importance in the development of mental diseases; however, in actual fact this does not seem to be justified. It is necessary to overcome this separation, in that social factors are incorporated into a conceptual framework in the development of mental diseases, which simultaneously also takes the results of current neurobiological research into consideration. OBJECTIVES AND METHODS: The aims of this review article are to summarize the current state of sociopsychiatric research and to emphasize the perspectives of the biological principles and their validity with respect to the social dimensions of psychiatry, as exemplified by schizophrenic disorders. The article presents the options for a biosocial approach in social psychiatry and gives an overview of the currently available literature. RESULTS AND CONCLUSION: There is an abundance of neurobiological research approaches, which are closely associated with sociopsychiatric topics, such as social cognition. Social psychiatry and biological psychiatry should no longer be considered as diametrically opposed subdisciplines. On the contrary, the options which could emerge from a synthesis must be used in research and clinical practice.

Medicalization in psychiatry: the medical model, descriptive diagnosis, and lost knowledge.

Medicalization was the theme of the 29th European Conference on Philosophy of Medicine and Health Care that included a panel session on the DSM and mental health. Philosophical critiques of the medical model in psychiatry suffer from endemic assumptions that fail to acknowledge the real world challenges of psychiatric nosology. The descriptive model of classification of the DSM 3-5 serves a valid purpose in the absence of known etiologies for the majority of psychiatric conditions. However, a consequence of the "atheoretical" approach of the DSM is rampant epistemological confusion, a shortcoming that can be ameliorated by importing perspectives from the work of Jaspers and McHugh. Finally, contemporary psychiatry's over-reliance on neuroscience and pharmacotherapy has led to a reductionist agenda that is antagonistic to the inherently pluralistic nature of psychiatry.  As a result,  the field has suffered a loss of knowledge that may be difficult to recover.

Forced Migration as Public Relations Process? Lothar B. Kalinowsky and the Trans-Atlantic Transfer of Electroconvulsive Therapy.

Research in biological psychiatry during the first half of the 20th century was based upon a wide range of interrelated disciplines, including neurology, neuroanatomy, neuropathology, and experimental biology. The work of German-American psychiatrist and neurologist Lothar B. Kalinowsky (1899-1992) is taken here as an example of how such fields could be combined to produce a highly innovative and multidimensional research program in clinical neuroscience. Kalinowsky functioned exceptionally well in both scientific and clinical cultures despite the marked contextual differences between the Charité in Berlin and his later workplace in New York's Columbia Medical School. The innovative ideas exemplified by Kalinowsky's efforts, however, sometimes amounted to a dubious advantage for émigré clinical neuroscientists: they easily led to incommensurable scientific views, and sometimes even resulted in the marginalization of the innovator from existing research programs.

Shortened telomere in unremitted schizophrenia.

AIM: Telomere attrition has been noted in many neuropsychiatric and neurodegenerative syndromes, and may indicate a shared molecular pathology across conditions. We evaluated telomere length in subjects with remitted and unremitted schizophrenia and in control subjects. METHODS: We measured telomere length as relative telomere/single-copy gene ratios in subjects with schizophrenia (n = 71) using quantitative real-time polymerase chain reaction. This was compared with relative telomere/single-copy gene ratios in age-matched controls without neuropsychiatric illness (n = 73). RESULTS: The relative telomere/single-copy gene ratios were significantly lower in subjects with unremitted schizophrenia when compared with control subjects (r = -0.281, P = 0.003), as well as the individuals with remitted schizophrenia. CONCLUSION: The lower relative telomere length in unremitted schizophrenia subjects may thus indicate shared biological pathways with other neurodegenerative disorders that are also characterized by increased cellular senescence.