Jaak Panksepp spent nearly five decades mapping the primary-process affective systems of the mammalian brain across different species, producing a framework of considerable empirical power that is functionally invisible within psychiatry. Psychiatry has not built upon that literature in human contexts. Consequently, Affect has never occupied the foundational place in psychiatry that the evidence warrants. This paper attempts to close that gap and assembles twelve converging lines of evidence for subcortical primacy of Affect, including evidence not previously synthesized for this purpose: pseudobulbar affect, gelastic and dacrystic epilepsy, double dissociation of volitional and emotional facial expression, affective blindsight, and neonatal emotional behavior. The evidence shows that Affect is generated subcortically, the cortex modulates rather than creates it, and when cortical regulation is removed or impaired, affective states persist or intensify. From this evidence, personality is best understood as an individual’s position in a configuration space defined by subcortical Affect generation parameters and cortical regulatory capacity, with psychopathology occurring when signal intensity chronically exceeds or overwhelms regulatory capacity. This framework generates a specific clinical prediction: conditions that co-occur with personality pathology at rates incompatible with independent etiology are expressions of the same affective architecture through different conditioned channels, not independent diseases. Evidence confirms this directly: when personality pathology improves, its comorbid conditions decline substantially; when it does not, they persist. Further, the affective-regulatory framework transforms the clinical encounter by replacing a character verdict with a neurobiologically grounded account in which regulatory capacity is buildable and recovery is construction rather than correction.
Psychological distress experiences among patients living with HIV: a qualitative systematic review
BackgroundHIV patients endure psychological distress throughout the phases of diagnosis, treatment, and rehabilitation, which considerably affects their quality of life. A thorough comprehension of patients’ psychological distress experiences is crucial for healthcare workers to devise focused solutions for enhanced care. This study aims to consolidate evidence concerning psychological distress in HIV patients and elucidate its sources and influencing factors.DesignA systematic review and meta-synthesis of qualitative studies.MethodsA thorough literature review was performed across eight electronic databases from inception to June 2025.Qualitative studies were selected if pertinent to the psychological distress experiences of HIV patients. The quality of qualifying studies was assessed utilizing JBI qualitative research quality evaluation standard. The thematic synthesis method was utilized to amalgamate the findings.ResultsA total of 1583 studies were identified through database research, and 11 studies were incorporated into the review. Three analytical themes emerged from the findings: individual factors including disease diagnosis and emotional dilemma; environmental factors including economic hardship, social environment and limited access to health support; interpersonal factors including decline in marital intimacy and insufficient support from family and friends.ConclusionPsychological distress is a subjective phenomenon influenced by the interaction of individual, environmental, and interpersonal factors, commonly seen in HIV patients. Effective therapeutic care requires understanding psychological distress prevalence and causes. Individualized, sustainable, and adaptive psychosocial care interventions should be taken to alleviate psychological distress, improve patients’ mental health and facilitate their reintegration into society.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/view, identifier CRD420251050269.
Disrupted sensory interhemispheric synchronization in schizophrenia: a frequency-resolved VMHC analysis
BackgroundAberrant interhemispheric functional connectivity has been implicated in the pathophysiology of schizophrenia. Voxel-mirrored homotopic connectivity (VMHC) provides a reliable measure of interhemispheric synchronization, yet the frequency-specific characteristics of VMHC alterations in schizophrenia remain poorly understood.MethodsResting-state functional magnetic resonance imaging data were analyzed in patients with schizophrenia and matched healthy controls. VMHC was computed across frequency bands, with particular focus on slow-4 and slow-5 oscillations. Group differences, as well as group-by-frequency interactions, were assessed to identify frequency-specific disruption.ResultPatients with schizophrenia exhibited significantly reduced VMHC within key sensory networks, including primary visual and sensorimotor regions. Frequency-specific analyses revealed higher VMHC at slow-5 compared with slow-4 in visual gyrus and subcortical regions. Significant group-by-frequency interaction effects were observed in the middle occipital gyrus and postcentral gyrus, with post-hoc analyses indicating selectively reduced slow-4 VMHC in patients with schizophrenia.ConclusionThis study demonstrates frequency-dependent reductions of interhemispheric connectivity in schizophrenia, particularly within sensory systems. The findings highlight the disrupted integration of primary perceptual and motor-related processes as a core feature of schizophrenia and emphasize the utility of frequency-resolved VMHC analyses for refining our understanding of network dysfunction. Future longitudinal studies are warranted to determine the clinical significance of these frequency-specific alterations in illness progression and treatment response.
Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial
Nature Medicine, Published online: 12 June 2026; doi:10.1038/s41591-026-04465-9
Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.
The Hong Kong Genome Project is a flagship initiative for precision medicine in Chinese populations
Nature Medicine, Published online: 12 June 2026; doi:10.1038/s41591-026-04421-7
The Hong Kong Genome Project established a genome sequencing database that provides improved diagnoses for patients and more efficient, population-tailored carrier status screening. Actionable pharmacogenomic variants were identified in almost all participants, informing drug prescriptions. This work establishes a genomic resource and a transferable model for equitable precision medicine in underrepresented populations worldwide.
General-purpose large language models outperform specialized clinical AI tools on medical benchmarks
Nature Medicine, Published online: 12 June 2026; doi:10.1038/s41591-026-04431-5
In an independent evaluation, frontier large language models outperformed specialized clinical artificial intelligence tools on medical knowledge, clinician alignment and real-world clinical queries.
Striatal pathways dissociably control action counting and goal-directed steering
Nature Neuroscience, Published online: 12 June 2026; doi:10.1038/s41593-026-02330-z
Striatal direct and indirect pathways jointly control how many actions are performed during counting, and how animals move toward specific goals. These pathways implement a push–pull controller for discrete action counting as well as continuous movement control.
An Interactive Digital Dashboard for Patient Monitoring and Management in a Continuity of Care Centre: Development and Preliminary Usability Evaluation Study
Background: Clinical dashboards are becoming important tools for managing and monitoring hospitalized patients across different wards. Moreover, careful attention to design, usability, and user interaction is essential for developing effective support tools for clinicians. Objective: This study aimed to describe the development, implementation, and preliminary evaluation of an interactive dashboard for patient monitoring and management in the Continuity of Care Centre (CCC). Methods: We developed a dashboard according to clinicians’ requests and the daily workflow of case managers. First, a CCC Data Mart was created to collect all patients’ information automatically extracted from the hospital’s data warehouse. However, case managers had the possibility to enter additional patient information in the dashboard using a dedicated form. Moreover, CCC physicians, nurses, and administrative staff were surveyed using 2 validated questionnaires, the System Usability Scale and the Questionnaire for User Interaction Satisfaction. The Situation Awareness Index was proposed to evaluate user awareness and task efficiency. Results: The first version of the CCC dashboard presented 4 panels with different types of information, both on the individual patient and on metrics related to the overall patient population. The first panel focused on patients’ data, such as demographic factors, admission, transfer, discharge wards (and their dates), etc. The importance of this panel was the possibility of viewing information collected from different sources within a single interface. The other 3 panels displayed different key performance indicators for the overall patient population and presented data both in the form of tables in the second panel and graphs in the third and fourth panels. After 3 months of daily use, a total of 15 participants, 10 nurses, 2 administrative staff members, and 3 physicians, were recruited for the dashboard evaluation. The average System Usability Scale score of the dashboard was 61.5 (SD 15.7) points, which indicates “OK to good” usability, and the median score obtained with the Questionnaire for User Interaction Satisfaction was 5.77 (IQR 4-7), with the highest results in usability (mean 6.33, SD 0) and learning (mean 6.01, SD 0.39). The overall Situation Awareness Index score was 4 points, with the highest score in “familiarity of dashboard” (mean 4.73, SD 1.66 points) and “arousal support” (mean 4.6, SD 1.8 points). Conclusions: We developed an interactive dashboard for patient monitoring and management, with positive evaluations from users across different questionnaires.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/65132239ee389a3c7f7757cc25f46d29" />
<![CDATA[Once-nightly regular-release lithium cuts kidney risk, maintains bipolar control, improves adherence, and guides safer serum levels.]]>
<![CDATA[Experts unpack why most psychiatric care relies on off‑label meds, how neuroscience guides safe polypharmacy, and what could reshape FDA approvals.]]>