







Patients with systemic lupus erythematosus (SLE) experience neuropsychiatric symptoms. The term neuropsychiatric SLE (NPSLE) is a generic term that refers to a series of neurological and psychiatric symptoms directly related to SLE. In approximately 30% of patients with neuropsychiatric symptoms, SLE is the primary cause (NPSLE), and symptoms manifest more frequently around SLE onset. Neurovascular and psychotic conditions can also lead to NPSLE. Pathogenesis of NPSLE is implicated in both neuroinflammatory and ischemic mechanisms, and it is associated with high morbidity and mortality. After diagnosing and assigning causality, NPSLE treatment is individualized according to the type of neuropsychiatric manifestations, type of the predominant pathway, activity of SLE, and severity of the clinical manifestations. There are many problems to be addressed with regards to the diagnosis and management of NPSLE. Controlled clinical trials provide limited guidance for management, and observational cohort studies support symptomatic, antithrombotic, and immunosuppressive agents. The purpose of this review was to provide a detailed and critical review of the literature on the pathophysiology, diagnosis, and treatment of NPSLE. This study aimed to identify the shortcoming in diagnostic biomarkers, novel therapies against NPSLE, and additional research needs.
High intelligence: A risk factor for psychological and physiological overexcitabilities
High intelligence is touted as being predictive of positive outcomes including educational success and income level. However, little is known about the difficulties experienced among this population. Specifically, those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body). The present study surveyed members of American Mensa, Ltd. (n=3715) in order to explore psychoneuroimmunological (PNI) processes among those at or above the 98th percentile of intelligence. Participants were asked to self-report prevalence of both diagnosed and/or suspected mood and anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and physiological diseases that include environmental and food allergies, asthma, and autoimmune disease. High statistical significance and a remarkably high relative risk ratio of diagnoses for all examined conditions were confirmed among the Mensa group 2015 data when compared to the national average statistics. This implicates high IQ as being a potential risk factor for affective disorders, ADHD, ASD, and for increased incidence of disease related to immune dysregulation. Preliminary findings strongly support a hyper brain/hyper body association which may have substantial individual and societal implications and warrants further investigation to best identify and serve this at-risk population.
Patient-reported treatment outcomes in ME/CFS and long COVID
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are persistent multisystem illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments may prove helpful in identifying management strategies that can improve patient care and generate new avenues for research. Here, we present the results of an ME/CFS and long COVID treatment survey with responses from 3,925 patients. We assess the experiences of these patients with more than 150 treatments in conjunction with their demographics, symptoms, and comorbidities. Treatments with the greatest perceived benefits are identified. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of long COVID reported postexertional malaise (PEM). Furthermore, treatment responses between these two patient groups were significantly correlated (R 2 = 0.68). Patient subgroups, characterized by distinct symptom profiles and comorbidities, exhibited increased responses to specific treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants. This study underscores the symptomatic and therapeutic similarities between ME/CFS and long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. While this study does not provide recommendations for specific therapies, in the absence of approved treatments, insights from patient-reported experiences provide urgently needed real-world evidence for developing targeted patient care therapies and future clinical trials.

Symptom Response to Low-Dose Naltrexone in Fibromyalgia: An Exploratory Analysis of the Randomized Placebo-Controlled FINAL Trial
Fibromyalgia (FM) remains difficult to manage due to a highly variable symptom profile. The “FINAL” randomized, placebo-controlled trial examined the efficacy of low-dose naltrexone (LDN) on pain in women with FM, showing no significant difference in pain reduction at the group level but potentially higher 30% pain response rates. Analysis of secondary outcomes showed potential improvements in memory problems.

Autistic Burnout vs. Depression | Neurodivergent Insights
Dr Megan Anna Neff explains the difference between autistic burnout and depression. Overlapping signs, root causes, and why withdrawal can be a valid response.

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder
Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.

Blood tests for mental health problems | Eiko Fried
A new paper was published yesterday on a blood test for schizophrenia, by the same research team that in 2021 published a paper on a blood test for depression . The papers and...

Occurrence of Psychosis and Bipolar Disorder in Individuals With ADHD Treated With Stimulants
This systematic review and meta-analysis evaluates the association between psychosis or bipolar disorder and stimulant treatment among individuals with attention-deficit/hyperactivity disorder.

Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study
Background There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. Methods In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12–30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. Findings We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80–1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69–1·30) among those with a history of psychosis. Interpretation Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis. Funding Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre.
Methylphenidate Treatment and Risk of Psychotic Disorder
This cohort study of a Finnish national multiyear birth cohort uses instrumental variable analysis to investigate whether methylphenidate alters the long-term risk of psychotic disorder in children with attention-deficit/hyperactivity disorder.

OpenAI shares data on ChatGPT users with suicidal thoughts, psychosis
The figure could mean potentially hundreds of thousands of users show signs of mental health distress weekly.

Mitchell Hashimoto (@mitchellh)
I strongly believe there are entire companies right now under heavy AI psychosis and its impossible to have rational conversations about it with them. I can't name any specific people because they include personal friends I deeply respect, but I worry about how this plays out. I lived through the great MTBF vs MTTR (mean-time-between-failure vs. mean-time-to-recovery) reckoning of infrastructure during the transition to cloud and cloud automation. All those arguments are rearing their ugly heads again but now its... the whole software development industry (maybe the whole world, really). It's frightening, because the psychosis folks operate under an almost absolute "MTTR is all you need" mentality: "its fine to ship bugs because the agents will fix them so quickly and at a scale humans can't do!" We learned in infrastructure that MTTR is great but you can't yeet resilient systems entirely. The main issue is I don't even know how to bring this up to people I know personally, because bringing this topic up leads to immediately dismissals like "no no, it has full test coverage" or "bug reports are going down" or something, which just don't paint the whole picture. We already learned this lesson once in infrastructure: you can automate yourself into a very resilient catastrophe machine. Systems can appear healthy by local metrics while globally becoming incomprehensible. Bug reports can go down while latent risk explodes. Test coverage can rise while semantic understanding falls. Changes happens so fast that nobody notices the underlying architecture decaying. I worry.
Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID
Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion. Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options. This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus. By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.

Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID
Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion. Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options. This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus. By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.

(PDF) Neuroendocrine, Autonomic and Metabolic Challenges in Hypermobile Ehlers-Danlos Syndrome- A Case Study on Hypoglycemia in a patient with Craniocervical Instability.. Medical Research Archives. [Online] 12-5
PDF | This report presents a compelling case of hypoglycemia in a 20-year-old female with craniocervical instability receiving chronic total parenteral... | Find, read and cite all the research you need on ResearchGate



Science flags paper that found AI chatbots help debunk conspiracy theories

We Need to Know More About How AI is Affecting Mental Health

Evaluation of Large Language Model Chatbot Responses to Psychotic Prompts

ChatGPT's free version is 26 times more likely to respond inappropriately to psychotic delusions

ChatGPT Has ‘Goblin’ Mania in the US. In China It Will ‘Catch You Steadily’

"AI Psychosis" in Context: How Conversation History Shapes LLM Responses to Delusional Beliefs