Childhood adversity, stress reactivity, and structural brain measures in stress-related/neurodevelopmental disorders, and their comorbidity: A large transdiagnostic cross-sectional study.

Childhood adversity (CA), including childhood adverse life events, increases the risk for development of psychiatric disorders later in life. Both CA and psychiatric disorders are associated with structural brain changes and dysfunctional hypothalamic-pituitary-adrenal-axis. However, many studies investigated single diagnostic and single regions of interest of the brain, and did not take stress reactivity into account.

Gut microbiota composition links to variation in functional domains across psychiatric disorders.

Objective: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity.

Methods: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals.

Genetic and Pharmacological Modulation of Cellular Proteostasis Leads to Partial Functional Rescue of Homocystinuria-Causing Cystathionine-Beta Synthase Variants.

Homocystinuria (HCU), an inherited metabolic disorder caused by lack of cystathionine beta-synthase (CBS) activity, is chiefly caused by misfolding of single amino acid residue missense pathogenic variants. Previous studies showed that chemical, pharmacological chaperones or proteasome inhibitors could rescue function of multiple pathogenic CBS variants; however, the underlying mechanisms remain poorly understood. Using Chinese hamster DON fibroblasts devoid of CBS and stably overexpressing human WT or mutant CBS, we showed that expression of pathogenic CBS variant mostly dysregulates gene expression of small heat shock proteins HSPB3 and HSPB8 and members of HSP40 family.

A transdiagnostic view on MDD and ADHD: shared cognitive characteristics?

Background: Major Depressive disorder (MDD) and Attention Deficit Hyperactivity Disorder (ADHD) are prevalent mental disorders that often co-occur. There is overlap in symptomatology between MDD and ADHD that complicates diagnostics and treatment selection. Hence, to aid diagnostics of single and comorbid disorders, we aimed to examine the discriminative power of common symptom measures and cognitive dysfunction to differentiate between participants diagnosed with MDD, ADHD, ADHD and comorbid MDD and without a mental disorder.

Association Between Personality Traits and Functional Limitations in Older Adults with Affective Disorders: A Cross Sectional Study.

Objectives: Personality traits and affective disorders are both related to functional limitations. It is unknown whether personality traits have an additional effect on functioning in older adults with affective disorders. We studied the association between personality traits and functioning within this group.

Brain structure and function link to variation in biobehavioral dimensions across the psychopathological continuum.

In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e.

Transdiagnostic psychiatry: Symptom profiles and their direct and indirect relationship with well-being.

Background: Heterogeneity and comorbidity in psychiatric disorders are common, however, little is known about the impact on well-being and the role of functional limitations. We aimed to identify transdiagnostic psychiatric symptom profiles and to study their association with well-being and the mediating role of functional limitations in a naturalistic psychiatric patient group.

Methods: We used four disorder-specific questionnaires to assess symptom severity within a sample of 448 psychiatric patients with stress-related and/or neurodevelopmental disorders and 101 healthy controls.

Striatal connectopic maps link to functional domains across psychiatric disorders.

Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188).

Galanin analogs prevent mortality from seizure-induced respiratory arrest in mice.

Objective: Sudden Unexpected Death in Epilepsy (SUDEP) accounts for 20% of mortality in those with recurrent seizures. While risk factors, monitoring systems, and standard practices are in place, the pathophysiology of SUDEP is still not well understood. Better knowledge of SUDEP and its potential mechanisms of action is crucial to reducing risk in this patient population and developing potential treatment options.

Neural correlates of repetitive negative thinking: Dimensional evidence across the psychopathological continuum.

Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders.

Amygdala sensitivity for negative information as a neural marker for negative memory bias across psychiatric diagnoses.

Self-referent negative memory bias is a known risk factor for depression, but recent evidence suggests its function as a transdiagnostic cognitive depressotypic marker. The amygdala's sensitivity for negative information is considered a neurobiological depressotypic marker. However, their relationship remains unknown.

Anhedonia as a transdiagnostic symptom across psychological disorders: a network approach.

Background: Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders.

Methods: We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients ( = 557).

Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET): Protocol for a Cross-sectional Comorbidity Study From a Research Domain Criteria Perspective.

Background: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories.

Effectiveness of late-life depression interventions on functional limitations: A systematic review.

Depression is one of the most prevalent mental disorders in older adults and leads to considerable decreases in health, well-being, and impaired functioning. Intervention studies have focused on the effects on symptomatic recovery, and most do not include functional recovery as an outcome. Reduction of functional limitations as a treatment goal in old-age psychiatry aligns with the values of older persons.

Depressive Symptoms Account for Loss of Positive Attention Bias in ADHD Patients: An Eye-Tracking Study.

Objectives: Depression and ADHD often co-occur and are both characterized by altered attentional processing. Differences and overlap in the profile of attention to emotional information may help explain the co-occurence. We examined negative attention bias in ADHD as neurocognitive marker for comorbid depression.

The Role of Perseverative Cognition for Both Mental and Somatic Disorders in a Naturalistic Psychiatric Patient Sample.

Objective: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients.

More-Than-Human and Deeply Human Perspectives on COVID-19.

This multi-authored contribution explores what the COVID-19 pandemic demands of critical inquiry with a focus on the more-than-human. We show how COVID-19 is a complex series of multispecies encounters shaped by humans, non-human animals, and of course viruses. Central to these encounters is a politics of difference in which certain human lives are protected and helped to flourish while others, both human and animal, are forgotten if not sacrificed.

Patterns of discordance of physical functioning in older persons; different associations for apathy and depression? Results from the NESDO-study.

Objectives: Discordance between self-reported functional limitations and performance-based physical functioning may have a negative impact in functional independence in older adults. We longitudinally examined baseline apathy- and depressive symptomatology as associates of discordance.

Method: 469 participants from the multi-site cohort study NESDO were included.

Frailty as a Predictor of Mortality in Late-Life Depression: A Prospective Clinical Cohort Study.

Objective: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients.

The Effect of Alexithymia on Attentional Bias Toward Emotional Stimuli in Depression: An Eye-Tracking Study.

Alexithymia-reflecting deficits in cognitive emotion processing-is highly prevalent in individuals with depressive disorders. Subsequently, mixed evidence for attentional bias is found in these individuals. Alexithymia may be a potential influencing factor for attentional bias in depression.

Is a Negative Attentional Bias in Individuals with Autism Spectrum Disorder Explained by Comorbid Depression? An Eye-Tracking Study.

Heightened attention towards negative information is characteristic of depression. Evidence is emerging for a negative attentional bias in Autism spectrum disorder (ASD), perhaps driven by the high comorbidity between ASD and depression. We investigated whether ASD is characterised by a negative attentional bias and whether this can be explained by comorbid (sub) clinical depression.

Could Frailty be an Explanatory Factor of the Association between Depression and Other Geriatric Syndromes in Later Life?

Objectives: This study aimed to investigate whether frailty could be an explanatory factor of the association between depression and the number of geriatric syndromes.

Methods: Cross-sectional baseline data from a cohort study (MiMiCS-FRAIL) were analyzed in a sample of 315 older adults. Depression was measured according to DSM-5 criteria and a self-report questionnaire (PHQ-9).

Negative Learning Bias in Depression Revisited: Enhanced Neural Response to Surprising Reward Across Psychiatric Disorders.

Background: Prior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders.

Negative memory bias as a transdiagnostic cognitive marker for depression symptom severity.

Background: Negative memory bias is a strong risk factor for the development and maintenance of depression. Recent evidence also found negative memory bias in other mental disorders. Here, we aim to: 1) assess the presence and strength of negative memory bias in a range of (comorbid) mental disorders, 2) investigate which disorder-specific symptoms are associated with negative memory bias, and 3) test whether negative memory bias might be a transdiagnostic mechanism.

Challenging the negative learning bias hypothesis of depression: reversal learning in a naturalistic psychiatric sample.

Background: Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population.