Research In Biological Psychiatry Research Articles

Examining the role of personality functioning in a hierarchical taxonomy of psychopathology using two years of ambulatory assessed data

The Hierarchical Taxonomy of Psychopathology (HiTOP) arranges phenotypes of mental disorders based on empirical covariation, ranging from narrowly defined symptoms to higher-order spectra of psychopathology. Since the introduction of personality functioning (PF) in DSM-5 and ICD-11, several studies have identified PF as a predictor of transdiagnostic aspects of psychopathology. However, the role of PF in the HiTOP classification system has not been systematically examined. This study investigates how PF can be integrated into HiTOP, whether PF accounts for transdiagnostic variance captured in higher-order spectra, and how its predictive value for future affective well-being (AWB) and psychosocial impairment (PSI) compares to the predictive value of specific psychopathology beyond PF. To this end, we examined two years of ambulatory assessed data on psychopathology, PF, PSI, and AWB of N = 27,173 users of a mental health app. Results of bass-ackwards analyses largely aligned with the current HiTOP working model. Using bifactor modeling, aspects of PF were identified to capture most of the internalizing, thought disorder, and externalizing higher-order factor variance. In longitudinal prediction analyses employing bifactor-(S-1) modeling, PF explained 58.6% and 30.6% of variance in PSI and AWB when assessed across one year, respectively, and 33.1% and 23.2% of variance when assessed across two years. Results indicate that personality functioning may largely account for transdiagnostic variance captured in the higher-order components in HiTOP as well as longitudinal outcomes of PSI and AWB. Clinicians and their patients may benefit from assessing PF aspects such as identity problems or internal relationship models in a broad range of mental disorders. Further, incorporating measures of PF may advance research in biological psychiatry by providing empirically sound phenotypes.

Classification, selfhood, and culture in the Diagnostic and Statistical Manual of Mental Disorders and the Psychodynamic Diagnostic Manual

AbstractFor decades, social scientists have critiqued the construction of knowledge in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). However, they have not conducted research with an alternate classification from psychoanalytic and psychodynamic practitioners known as the Psychodynamic Diagnostic Manual (PDM), which is beginning to disseminate globally. This article analyzes cultural assumptions underpinning the classification rationale, concept of the self, and relationship between culture and mental disorders through close readings of DSM‐5‐TR (2022) and PDM‐2 (2017). It shows that DSM‐5‐TR's notion of scientific evidence is informed by an emphasis on biological research in psychiatry, which PDM‐2 views as mostly irrelevant to clinical work. Instead, PDM‐2 claims to speak authoritatively for the inner experiences of patients and clinicians in the therapeutic relationship. Both classifications share a concept of an ideal self that is individualistic, consistent across time, able to narrate rather than just feel emotions, and in control of cognition, emotion, and relationships. Whereas DSM‐5‐TR views the culture concept as a lens to interpret the patient–clinician encounter, PDM‐2 uses the culture concept inconsistently. I situate these findings within extant anthropological research and propose new directions to examine how both classifications are used in local contexts.

Diversity, Equity, and Inclusivity in Biological Psychiatry Research

Diversity, Equity, and Inclusivity in Biological Psychiatry Research

Decision-making as transdiagnostic construct for mental health research

Transdiagnostic research and linking behavioral, neural, and symptom measures are important endeavors in clinical neuroscience and biological psychiatry. In this issue of Neuron, Moutoussis etal. (2021) describe a new cognitive construct-decision acuity-that is related to mental health symptoms and distinct resting-state networks.

Attachment Insecurity in Rats Subjected to Maternal Separation and Early Weaning: Sex Differences.

Attachment insecurity in the forms of attachment anxiety and avoidance is associated with mental disorders in humans. In this research field, rodents, especially mice and rats, are commonly used to study social behaviors and underlying biological mechanisms due to their pronounced sociability. However, quantitative assessment of attachment security/insecurity in rodents has been a major challenge. The present study identified attachment insecurity behaviors in rats subjected to maternal separation (MS) during postnatal days (PD) 2–16 and early weaning (EW) during PD 17–21. This MSEW procedure has been used to mimic early life neglect in humans. After MSEW, rats continued to survive until early adulthood when they were subjected to open-field, social interaction, and elevated-plus maze tests. Compared to CNT rats in either gender, MSEW rats moved longer distances at higher velocities in the open-field. The MSEW rats also showed lower ratios of travel distance at central zone over that on whole arena of the open-field compared to CNT rats. In social interaction test, male CNT rats preferred to investigate an empty cage than females; whereas female CNT rats spent more time with a partner-containing cage as compared to males. This gender-specific difference was reversed in MSEW rats. On elevated-plus maze female CNT rats exhibited more risk-taking behaviors as compared to male counterparts. Moreover, female MSEW rats experienced a greater difficulty in making a decision on whether approaching to or averting from which arms of elevated-plus maze. Taken together, male MSEW rats behaved like attachment anxiety while females’ phenotype is alike to attachment avoidance described in humans. These results shall prompt further application of MSEW rat in abnormal psychology and biological psychiatry research.

Resilience Embodied: A Paradigm Shift for Biological Research in Psychiatry

Resilience Embodied: A Paradigm Shift for Biological Research in Psychiatry

Dopamine-Related Measurements From Both IPSC-Derived Dopaminergic Neurons and [18F]-FDOPA PET in Patients With Gaucher Disease With and Without Parkinsonism

Derivation of dopaminergic neurons from patients' induced pluripotent stem-cells (iPSCs) can enhance our understanding of the biology of dopamine-related illnesses, such as schizophrenia and Parkinson disease (PD), and provide transformative information for biological psychiatry research. However, whether dopaminergic properties of these neurons capture interindividual variation in central dopamine functioning is unknown. [18F]-FDOPA PET measures presynaptic dopamine synthesis capacity and vesicular storage, identifying hallmark diminished striatal dopaminergic content in idiopathic PD. Since mutations in GBA1, the gene implicated in Gaucher disease (GD), are an important risk factor for parkinsonism, we evaluated individuals with both GD and a family history of PD, testing for correspondence between dopamine-related measurements from both iPSC-derived neurons and molecular neuroimaging of the living brain.

The PsyCourse Infrastructure as an Example for Longitudinal Research in Biological Psychiatry

Both genetic and environmental factors play a major role in the etiology of mental illnesses. Longitudinal studies collecting many phenotypes and biomaterials help to elucidate this complex interplay. PsyCourse is an observational longitudinal multi-center (19 centers) study of severe mental disorders conducted in Germany and Austria, that, to date, collected data from more than 1,500 patients and control individuals. Here, we give an overview of the key properties and, specifically, the infrastructure of the PsyCourse study. Beside the study protocol, we provide information on IT tools, data management, data protection, quality control, data analysis, and data sharing with collaborators. We also highlight the need for fundamental preparation.

From Stress Sensitization to Microglial Priming and Vice Versa: A New Era of Research in Biological Psychiatry

From Stress Sensitization to Microglial Priming and Vice Versa: A New Era of Research in Biological Psychiatry

Making Sense of … the Microbiome in Psychiatry.

Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota, with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract; thus, it is not surprising that the most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body. The human gut microbiome has been shown to influence many aspects of host health, including more recently the brain.Several modes of interaction between the gut and the brain have been discovered, including via the synthesis of metabolites and neurotransmitters, activation of the vagus nerve, and activation of the immune system. A growing body of work is implicating the microbiome in a variety of psychological processes and neuropsychiatric disorders. These include mood and anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and even neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Moreover, it is probable that most psychotropic medications have an impact on the microbiome.Here, an overview will be provided for the bidirectional role of the microbiome in brain health, age-associated cognitive decline, and neurological and psychiatric disorders. Furthermore, a primer on the common microbiological and bioinformatics techniques used to interrogate the microbiome will be provided. This review is meant to equip the reader with a primer to this exciting research area that is permeating all areas of biological psychiatry research.

A Perspective on a Possible Relation Between the Psychopathology of the Schizophrenia/Schizoaffective Spectrum and Unconjugated Bilirubin: A Longitudinal Protocol Study.

Some authors suggest a relation between Unconjugated Bilirubin (UCB) plasma high levels and schizophrenia, as schizophrenia patients have been showing higher UCB levels when compared with other psychiatric patients and general population. These higher UCB levels have been already correlated with acute psychotic states, positive symptoms, and poor outcome in patients with schizophrenia. Schizophrenia and schizoaffective disorders share common symptoms but there aren't yet accepted biomarkers for their distinction. In our study protocol we propose an observational longitudinal study on a sample composed of two subgroups: patients with schizophrenia and patients with schizoaffective disorder. We will compare the UCB levels between groups, and search for a possible correlation with patient's psychopathology. For that purpose we will use nosological, psychopathological, neuropsychological, and psychosocial instruments. Thus we will be testing two different hypotheses: (1) Is UCB serum level a diagnosis indicator, with categorical distinction potential, between groups of patients with different psychotic disorders? (2) Is UCB serum level a severity indicator, with dimensional distinction potential, among groups of patients with the same psychotic disorder? We believe that UCB mean levels may contribute to some clarification of this controversy, as a potential biological indicator, facilitating the distinction between these two diagnostic categories and\\or discriminating the dimensional severity among each of these psychotic conditions. Thus we may be opening a new opportunities for innovative and exciting biological psychiatry research regarding organic aspects in the schizophrenia spectrum.

The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.

Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.

The need for new ontologies in psychiatry

Although researchers in psychiatry have been trying for decades to elucidate the pathophysiology underlying mental disorders, relatively little progress has been made. One explanation for this failure is that diagnostic categories in psychiatry are unlikely to track underlying neurological mechanisms. Because of this, the US National Institutes of Mental Health (NIMH) has recently developed a novel ontology to guide research in biological psychiatry: the Research Domain Criteria (RDoC). In this paper, I argue that while RDoC may lead to better neuroscientific explanations for mental disorders, it is unlikely that this new knowledge will then lead to an improved diagnostic system. I therefore suggest that researchers in psychiatry should work toward the development of two new ontologies: one for research and one for clinical practice.

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.

Machine learning, statistical learning and the future of biological research in psychiatry.

Psychiatric research has entered the age of 'Big Data'. Datasets now routinely involve thousands of heterogeneous variables, including clinical, neuroimaging, genomic, proteomic, transcriptomic and other 'omic' measures. The analysis of these datasets is challenging, especially when the number of measurements exceeds the number of individuals, and may be further complicated by missing data for some subjects and variables that are highly correlated. Statistical learning-based models are a natural extension of classical statistical approaches but provide more effective methods to analyse very large datasets. In addition, the predictive capability of such models promises to be useful in developing decision support systems. That is, methods that can be introduced to clinical settings and guide, for example, diagnosis classification or personalized treatment. In this review, we aim to outline the potential benefits of statistical learning methods in clinical research. We first introduce the concept of Big Data in different environments. We then describe how modern statistical learning models can be used in practice on Big Datasets to extract relevant information. Finally, we discuss the strengths of using statistical learning in psychiatric studies, from both research and practical clinical points of view.

Practice relevant research in biological psychiatry

The practice of psychiatry would be unthinkable without modern psychopharmacology. Drug treatment, especially of severe psychiatric disorders, is often a precondition of community participation, societal reintegration and recovery. Seen in this context it is understandable that biological psychiatry has long been primarily defined by its close interconnection with psychopharmacology and has been perceived this way by practicing physicians. In recent years, however, the concept of what is "biological" has markedly expanded and so has the outreach of this approach into the practice of psychiatry. This article discusses examples showing that biological research methods provide new impulses for individualized medicine, psychotherapy and understanding environmental risks and therefore provide the basis for a preemptive and preventive approach that will be the key to master the challenges posed by the severe burden of mental illness.

Mental disorder: a public health problem stuck in an individual-level brain disease perspective?

Mental disorder: a public health problem stuck in an individual-level brain disease perspective?

Gaining translational momentum: More zebrafish models for neuroscience research

Zebrafish (Danio rerio) are rapidly becoming a popular model organism in translational neuroscience and biological psychiatry research. Here we discuss conceptual, practical and other related aspects of using zebrafish in this field ("from tank to bedside"), and critically evaluate both advantages and limitations of zebrafish models of human brain disorders. We emphasize the need to more actively develop zebrafish models for neuroscience research focusing on complex traits.

Deranged serum cholesterol levels in first episode mania.

Dear Editor, Low cholesterol and triglyceride levels have been reported in patients with affective disorders, both in actively symptomatic and remitted states.[1,2] Though the phenomenon is not completely understood, this abnormality is well-established in the Western population.[1,2,3] However, the generalizability of these results to the developing world remains questionable as the two populations differ significantly with respect to their physiology, physical activity, socioeconomic status, lifestyle, and food habits. As a part of an ongoing study, we recruited 50 consecutive male patients with first episode mania (International Classification of Diseases – 10, Diagnostic Criteria for Research (ICD-10 DCR), World Health Organization, 1993), who attended the outpatient department of a tertiary care psychiatric institute located in the eastern part of India. This institute caters to the needs of a large population from adjoining states of central, northern and north-eastern part of the country in addition to the local populace. All subjects were either “drug-free” (n = 21; drug free for at least 4 weeks in patients receiving oral psychotropic medications or 8 weeks in patients receiving depot medications, prior to recruitment) or “drug-naive” (n = 29; patients who never received any psychotropic medication in the past). Neither of the patients suffered from any neurological, medical, or substance-related comorbidity, nor did they have any chronic illness that may have affected their blood lipid levels. The study was approved by the institute's ethical committee, and all participants gave valid and informed consent for the study. After a 12-hour fast, morning venous blood samples were drawn. Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, and triglycerides were measured. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. The mean age of our study sample was 26.94 ± 6.94 years and mean value of BMI was 18.59 ± 2.35 kg/m2. Subjects had a mean TC level of 136.06 ± 35.47 mg/dL, Triglyceride of 87.28 ± 38.73 mg/dL, HDL of 38.50 ± 8.71 mg/dL, LDL of 82.14 ± 30.56 mg/dL, and VLDL of 17.04 ± 7.67 mg/dL [Table 1]. Table 1 Comparison of mean lipid and cholesterol values between study sample and control population We compared our findings to available normal values of a population belonging to the same age (21-30 years) and sex group (male) described from western part of India.[4] The characteristics of control population and our subject group were similar, being free of major medical or substance related comorbidities (including absence of obesity i.e., BMI <30 kg/m2). Further, the controls did not suffer from any major psychiatric disorders and belonged to lower and middle income families, also similar to our subjects.[4] Finally, both studies used fasting serum samples to measure lipid profile. Independent sample t-test yielded a significant (P < 0.001) difference in the TC, HDL, and LDL levels between the two groups, being lower in patients with mania [Table 1]. There was no statistically significant difference in the triglyceride and VLDL levels between the two groups, although they were lower in the manic group. Hence, present findings corroborate with available literature[1,2] and are, to the best of our knowledge, the first report from an Indian study. These findings are of importance because the population these patients represent differs considerably from the Western world (on which past results were primarily based). Recent research in biological psychiatry suggest that serum cholesterol may be a surrogate marker for impulsivity,[5] and lower levels of TG and LDL have been demonstrated to predict significantly increased impulsivity in psychiatric patients.[6,7] Hence, bearing in mind that high scores on measures of impulsivity pose considerable risk for suicide and other self-harming behaviors,[8] the finding of reduced baseline cholesterol levels in patients with first episode mania is noteworthy. Patients presenting with low cholesterol and mood symptoms need increased clinical attention and surveillance. It may also warrant increased caution while implementing interventions aimed at lowering serum lipids, using statins and fibrates. Our findings are, however, preliminary in this regard. The sample consisted only of male patients and lacked an internal control. Furthermore, it may be difficult to generalize the findings to other parts of India since significant variability prevails between the regions with respect to lifestyle, food habit, and so on Future studies with a larger sample size, with inclusion of female patients and an internal control are suggested.

Rating scale of handedness for biological psychiatry research among Japanese people

Rating scale of handedness for biological psychiatry research among Japanese people