Parkinson's disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms^1-5. Dysfunction of the somato-cognitive action network (SCAN)-which is thought to control action execution^6,7 by coordinating arousal, organ physiology and whole-body motor plans with behavioural motivation-is a potential contributor to the diverse clinical manifestations of PD. To investigate the role of the SCAN in PD pathophysiology and treatments (medications, deep-brain stimulation (DBS), transcranial magnetic stimulation (TMS) and MRI-guided focused ultrasound stimulation (MRgFUS)), we built a large (n = 863), multimodal, multi-intervention clinical imaging dataset. Resting-state functional connectivity revealed that the substantia nigra and all PD DBS targets (subthalamic nucleus, globus pallidus and ventral intermediate thalamus) are selectively connected to the SCAN rather than to effector-specific motor regions. Importantly, PD was characterized by specific hyperconnectivity between the SCAN and the subcortex. We therefore followed six PD cohorts undergoing DBS, TMS, MRgFUS and levodopa therapy using precision resting-state functional connectivity and electrocorticography recording. Efficacious treatments reduced SCAN-to-subcortex hyperconnectivity. Targeting the SCAN instead of effector regions doubled the efficacy of TMS treatments. Focused ultrasound treatment benefits increased when the target was closer to the thalamic SCAN sweet spot. Thus, SCAN hyperconnectivity is central to PD pathophysiology and its alleviation is a hallmark of successful neuromodulation. Targeting functionally defined subcortical SCAN nodes may improve existing therapies (DBS, MRgFUS), whereas cortical SCAN targets offer effective non-invasive or minimally invasive neuromodulation for PD.

Candidates for metabolic bariatric surgery (MBS) experience significantly higher rates of mental disorders compared to the general population. While previous studies have primarily focused on a limited range of mental health conditions, this study expands the scope by studying a broader spectrum of psychopathological symptoms. Our aim was to map the psychopathological profile of candidates for MBS and to test whether individuals higher in general psychopathology exhibit a higher body mass index (BMI) and more severe eating disorder symptoms than those lower in general psychopathology.

A total of 222 candidates for MBS from the Dutch Obesity Clinic completed 16 questionnaires to generate a comprehensive psychopathological profile. Cluster analysis was applied to identify distinct groups based on general psychopathology. The clusters were compared on BMI and eating disorder psychopathology. A cross-sectional network approach was used to explore the complex interconnections between symptoms.

Two clusters emerged: a high psychopathology profile (high PP; 29%) characterized by elevated scores on general psychopathology, and a low psychopathology profile (low PP; 71%) marked by healthier psychological functioning. The high PP cluster exhibited more severe eating disorder psychopathology than the low PP cluster, while the clusters did not differ in BMI. The symptom network revealed that general psychopathology is linked to eating disorder psychopathology through the bridge symptom 'eating concerns.'

Approximately one-third of the individuals presenting for MBS exhibit elevated, transdiagnostic psychopathology with complex connections between symptoms. Notably, BMI was not associated with the severity of symptoms. The symptom network analysis highlights that 'eating concerns' serve as a crucial bridge linking eating disorder symptoms and symptoms of emotional disorders. Future research should focus on the transdiagnostic nature of psychopathology associated with obesity and investigate its potential impact on treatment outcomes, such as weight loss and quality of life.

This study aimed to evaluate time-of-day-specific functional impairments in children with obsessive-compulsive disorder (OCD) and identify related clinical and psychosocial factors. The registry data for a total of 136 children diagnosed with OCD was analyzed. Questionnaire - Children with Difficulties (QCD) was used to assess functional difficulties across daily lives and was reported by the parents. The QCD scores of the children with OCD were compared with community norms. Multiple regression analyses were used to examine the associations of the QCD domains with age, weekday sleep, anxiety, depression, behavioral problems, and siblings. The mean age of patients in the OCD group was 11.46 years (SD = 2.27), with 69 boys (51.1%) and 66 girls (48.9%). The children with OCD scored significantly lower across all QCD domains (all p < .01), with large effects for night (d = - 2.04), total QCD (d = - 2.10), school (d = - 1.90), and after-school (d = - 2.03) compared to the community sample. In the regression analyses, higher behavioral problem scores predicted better functioning in the morning and evening, whereas a greater number of siblings predicted poorer morning functioning. Higher anxiety scores were significantly associated with better night-time functioning. However, depressive symptoms were not significantly associated with overall functioning. Children and adolescents with OCD demonstrated marked domain-specific functional impairments, particularly during school, after school, and nighttime routines. Distinct psychosocial factors, including behavioral problems, sibling presence, and anxiety symptoms, were associated with time-specific functioning, underscoring the need for targeted, time-sensitive interventions.

Schizophrenia genome-wide association studies (GWASes) have identified >250 significant loci and prioritized >100 disease-related genes. However, gene prioritization efforts have mostly been restricted to locus-based methods that ignore information from the rest of the genome. To more accurately characterize genes involved in schizophrenia etiology, we applied a combination of highly-predictive tools to a published GWAS of 67,390 schizophrenia cases and 94,015 controls. We combined both locus-based methods (fine-mapped coding variants, distance to GWAS signals) and genome-wide methods (PoPS, MAGMA, ultra-rare coding variant burden tests). We extracted genes that 1) are targeted by existing drugs that could potentially be repurposed for schizophrenia, 2) are predicted to be druggable, or 3) may be testable in rodent models. We prioritized 101 schizophrenia genes, including 15 that are targeted by approved or investigational drugs (e.g., DRD2, GRIN2A, CACNA1C, GABBR2). Of these, 7 have never been tested in clinical trials for schizophrenia or other psychiatric disorders (e.g., AKT3). Seven genes are not targeted by any existing small molecule drugs, but are predicted to be druggable (e.g., GRM1). We prioritized two potentially druggable genes in loci that are shared with an addiction GWAS (PDE4B and VRK2). We curated a high-quality list of 101 genes that likely play a role in the development of schizophrenia. Developing or repurposing drugs that target these genes may lead to a new generation of schizophrenia therapies. Rodent models of addiction more closely resemble the human disorder than rodent models of schizophrenia. As such, genes prioritized for both disorders could be explored in rodent addiction models, potentially facilitating drug development.

Transcriptomic studies of post-mortem brain samples in schizophrenia (SCZ) and bipolar disorder (BD) have primarily focused on messenger RNAs (mRNAs) but have given limited attention to small non-coding RNAs (sncRNAs). In this study, we present our analyses of sncRNA profiles from the prefrontal cortex of SCZ and BD cases and controls (53 SCZ cases, 40 BD cases, 77 controls), which we sourced from the Icahn School of Medicine at Mount Sinai and the NIMH Human Brain Collection Core brain banks. Corresponding mRNA-seq data were obtained from the CommonMind Consortium. Using a state-of-the-art pipeline, we mapped reads and determined differentially abundant and co-expressed sncRNAs and mRNAs, adjusting for known and hidden confounders. Across samples, 98% of all sncRNAs comprised miRNA isoforms (60.6%), tRNA-derived fragments (17.8%), rRNA-derived fragments (11.4%), and Y RNA-derived fragments (8.3%). In SCZ, 15% of the identified sncRNAs exhibited significant fold changes (FCs), with many also altered in BD, albeit to a lesser extent. For miRNAs, the FCs correlated strongly with the presence of non-templated nucleotides to their 3'-ends, independently of miRNA identity or locus of origin. Disease- and age-associated sncRNAs and mRNAs revealed accelerated aging in both SCZ and BD. Co-expression analyses also revealed, for the first time, disease-independent associations of many isomiRs, tRFs, rRFs, and yRFs with critical brain processes. These findings suggest complex and previously uncharacterized roles for novel classes of regulatory sncRNAs in synaptic signaling, neurogenesis, memory, behavior, and cognition.

Self-reported symptoms of anxiety and depression may help identify at-risk groups and examine mental health trends on the population level. This study examined sex-specific secular and longitudinal trends in mental health among Norwegian older adults.

Data from the Tromsø Study (2001, 2007-2008, 2015-2016) were analyzed. Secular trend analyses involved 12,884 individuals aged 60-84 years (19,631 observations). Longitudinal trends analyses included a subset of 8,766 individuals born between 1917-1947. Depression and anxiety symptoms were measured using the HSCL-10. Scores ≥ 1.85 were used to identify cases with mental distress, a predictor for clinically diagnosed mental disorders. Linear mixed regression and multiple imputation were used for analysis.

From 2001 to 2016, age-adjusted proportions of mental distress among participants aged 60-84 years declined (overall: 9.8 % to 6.6 %, women: 13.7 % to 8.9 %, men: 5.0 % to 4.0 %). Secular trends revealed lower average symptom scores in 2016 than in 2001, particularly in anxiety symptoms and among women. The youngest birth cohorts (1942-1947) experienced the largest longitudinal reductions in HSCL-10 scores; -0.08 (95% confidence interval [CI]: -0.11, -0.04) among women, and -0.04 (95% CI: -0.08, -0.01) among men. The largest increase in HSCL-10 score occurred during 2001-2008 among women born 1917-1921 and among men born between 1922-1931.

Mental distress prevalence among older adults declined from 2001 to 2016. Mental health trends appear to be driven by reduced anxiety scores. Women exhibited stronger trends, narrowing sex differences in mental distress. Further research is needed to elucidate these trends.

Outpatient postpartum recovery remains poorly understood. We aimed to characterize postpartum recovery and compare recovery by delivery mode and parity using with the newly validated STanford Obstetric Recovery checKlist (STORK).

Following institutional review board approval, English-speaking adults were recruited from three U.S. academic centers. Demographic and clinical data were collected. Participants completed STORK (47 items covering physical, mental/emotional health, motherhood experience/social support, sleep/fatigue domains), at two, six and 12 weeks postpartum. Chi-square, one-way ANOVA, and Kruskal-Wallis tests were used to compare categorical and continuous variables.

A total of 498 participants were included (Asian 15%, Black 8%, White 51%), mean age 33±5years. Median gestational age was 39 weeks (IQR 2), and 46% were primiparous. Spontaneous/induced vaginal delivery (SVD), scheduled cesarean delivery (CD), non-scheduled CD, and operative vaginal delivery (OVD) represented 52%, 27%, 18% and 3% of participants, respectively. Total STORK, physical health, and sleep/fatigue scores improved from inpatient postpartum period to week 12 postpartum (P<0·001) for all delivery modes, with a 22% increase in median total scores. Mental health and motherhood experience scores improved until week six (P<0·001). Physical recovery scores differed significantly between delivery modes, with best scores after SVD and lowest after OVD up to week two. Overall recovery was better in multiparous compared to primiparous patients up to six weeks postpartum, though differences resolved by week 12.

Postpartum recovery continues through 12 weeks and varies by delivery mode and parity. Future studies are needed to determine clinically meaningful differences to inform thresholds for targeted interventions.

Early difficulties in the regulation of emotion, sleep and eating are common in early childhood and may shape developmental pathways of eating behaviours and weight. Understanding these pathways is key to identifying modifiable targets for promoting healthy eating and growth. This systematic review aimed to synthesise available evidence linking regulatory problems (RPs) of emotion, sleeping, and eating in early childhood to feeding, eating, and weight outcomes and evaluate methodological quality and level of evidence using the National Institutes of Health Quality Assessment Tool and best evidence synthesis. We searched MEDLINE, EMBASE, and PsycINFO for studies published in English from inception to September 2025. Eligible studies included children aged 3-36 months with a measure of RP and either parental feeding practice, child eating behaviour, or weight. Methodological quality was assessed, and a narrative synthesis undertaken. Thirty-eight studies were eligible for inclusion. Most were of moderate quality (n=33). According to best evidence synthesis, there was insufficient level of evidence for associations between emotion regulation and feeding, eating, and weight. There was moderate level of evidence for a cross-sectional association between sleep problems and eating behaviour, and of no association with weight. There was moderate level of evidence for an association between eating problems and feeding and weight. This review provides novel evidence that, while eating problems in early childhood are linked to feeding practices and weight, the evidence is less clear on the role of emotion and sleep regulation difficulties in shaping these trajectories. By highlighting early childhood as a critical yet underexplored period, our findings underscore the need for high-quality longitudinal research with homogeneous methodology to clarify whether early-life RPs represent modifiable intervention targets supporting healthy feeding, eating, and weight. PROSPERO REGISTRATION NUMBER: CRD42023463391.

Cognitive impairment is a serious pathological feature of neuropsychiatric disorders, making the exploration of effective treatments urgent. Recent research shows that combined transcranial electrical stimulation (tES) and cognitive training (CT) can reduce cognitive deficits. This review summarizes studies on neurological disorders that use both clinical patients and rodent models to highlight the underlying neural mechanisms. In patients, this combined approach improves cognitive domains such as attention, working memory, and executive function. Improvements have been observed in patients with mild cognitive impairment (MCI), dementia (e.g., Alzheimer's disease (AD)), Parkinson's disease (PD), stroke, traumatic brain injury (TBI), multiple sclerosis, schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, as well as in healthy populations. In contrast, studies on the combined intervention are lacking in rodent models of disease. However, tES and CT separately improve spatial learning and memory in AD, TBI, schizophrenia, ADHD, and healthy animals, as well as in models of vascular dementia and cerebral ischemia. The combined intervention regulates and remodels functional connectivity in brain networks, and improves cerebrovascular microcirculation and glutamatergic neurotransmission. Importantly, tES and CT may enhance each other through cooperative and complementary effects. In addition, some studies have reported the limited efficacy or negative outcomes of combined and single interventions, which may be due to suboptimal parameters or techniques that fail to target key pathologies. Future clinical trials should explore tES-CT combination strategies targeting disease-specific brain regions. Furthermore, animal studies must be strengthened to elucidate the potential mechanisms and interactions of tES and CT.