Search Results (3,599)

Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone leptin, are reliable biomarkers for the estimation of alcohol dependence and abstinence. AUD outpatients (N = 122) and healthy volunteers (N = 63) were recruited and assessed by using the Psychiatric Research Interview for Substance and Mental Disorders according to DSM-IV-TR after blood extraction. The results indicated that AUD patients had higher plasma concentrations of LPS and HMGB1, and lower plasma concentrations of leptin and SDF-1α compared to healthy subjects. Two logistic models, including HMGB1, leptin and SDF-1α (model 1) or LPS (model 2), provided high discriminatory powers to identify AUD patients [prognostic probability: model 1 = 0.90 (0.78); model 2 = 0.86 (0.79); p < 0.001]. LPS and HMGB1 positively correlated with alcohol abstinence duration in male AUD patients only. Linear logistic regression included LPS, HMGB1, fractalkine, SDF-1α and/or leptin to accurately estimate the duration of problematic alcohol use and alcohol abstinence when sexes were analyzed separately. These results suggest that LPS and HMGB1 are relevant sex-specific actors for predicting alcohol abstinence and problematic alcohol use in AUD patients. Full article

Heart rate variability (HRV) refers to variations in the time intervals between consecutive heart beats. Changes in HRV reflect changes in either sympathetic or decreased parasympathetic tone that can originate in the brain. This brain–heart connection has led to the proposal that HRV may have utility in the diagnosis of psychiatric conditions and/or be a predictor of the response to psychiatric medications. There have been attempts to improve the correlation between HRV and psychological and psychiatric conditions by using artificial intelligence or specific machine learning algorithms. The objective of this review is to synthesize data on the use of machine learning to improve accuracy in differentiating psychological conditions such as mental stress, as well as distinguishing persons with anxiety disorders, panic disorders, major depression disorders and schizophrenia from health subjects. Reported accuracies for the identification of mental stress vary from 42 to 94%, while accuracies for anxiety vary from 67 to 98%, panic disorders from 71 to 93% and depression from 71 to 95%. The ability of HRV to differentiate different psychological or psychiatric conditions from each other requires more investigation. The ‘best’ machine learning algorithm varied between studies, with some reporting the k-nearest neighbor algorithm, support vector machine, random forest, or neural networks to be the best. A number of studies combined HRV with other variables such as respiration, EEG, or electromyography to obtain a composite index, but in doing so obscured the independent contribution of HRV. In summary, HRV has shown promise in detecting abnormalities in a range of psychological and psychiatric conditions. The use of machine learning algorithms improves diagnostic accuracy. Full article

Severe mental disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), are leading causes of global disability, yet current treatments remain largely symptomatic and fail to alter disease trajectories. Converging evidence from genetics, longitudinal studies, and systems neuroscience supports a dimensional and transdiagnostic architecture of psychopathology, involving shared polygenic risk and overlapping neurodevelopmental and circuit-level alterations. Traditional approaches—such as post-mortem brain analysis, neuroimaging, and animal models—have delineated core molecular perturbations (e.g., dopaminergic, glutamatergic, and GABAergic dysfunction), as well as informed translational frameworks for mechanistic investigation, but remain constrained by restricted access to dynamic processes and incomplete recapitulation of human-specific biology. The advent of human-derived cellular models, particularly human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), has partially addressed these limitations, enabling the study of patient-specific neurodevelopment and synaptic function in vitro. Within this evolving landscape, the olfactory neuroepithelium (ONE) has emerged as an accessible source of neural progenitors, obtainable through minimally invasive procedures, providing a window into living human neurobiology. ONE-derived cells retain donor-specific genetic and epigenetic signatures while recapitulating disease-relevant phenotypes across major psychiatric disorders, including altered neurodevelopmental dynamics, synaptic gene expression, and inflammatory profiles. Here, we present a narrative review of the principal cellular and tissue models used in biological psychiatry, examining their respective strengths, limitations, and translational relevance across experimental contexts. By situating these approaches within a unified framework, we aim to clarify their complementarity, identify current gaps, and outline future directions, highlighting the emerging potential of ONE-based models to bridge genetic risk, cellular dysfunction, and clinical phenotype, thereby advancing precision psychiatry. Full article

Background: Psychiatric assessments traditionally rely on the Diagnostic and Statistical Manual of Mental Disorders (DSM) for diagnostic guidance. This approach, however, is heavily based on the identification of cluster symptoms assessed through subjective interviews and questionnaires, without adequately controlling for overlapping symptoms or symptom specificity. This may lead to broad and often inaccurate diagnoses that overlook the patient’s unique experience and underlying neurobiological imbalances. As mental healthcare strives to move towards personalized medicine, incorporating more objective and precise measures of neuropsychological distress, it is essential to reduce the diagnostic and treatment inaccuracies that may stem from relying solely on empirical guidelines. This narrative review examines the limitations of the current approach and considers the potential role of quantitative electroencephalography (qEEG) as an adjunctive method that may enrich existing diagnostic processes. Methods: A structured literature search was conducted in Europe PMC on 31 January 2026. Original human studies and clinical trials in English with available abstracts were thematically selected. Results: The search yielded 1934 records, from which a focused subset of studies was selected based on direct relevance to the review themes. Conclusions: Integrating qEEG methods into traditional assessments could enhance diagnostic accuracy in psychiatric care and reduce patients’ exposure to inadequate treatments, ultimately leading to improved treatment outcomes and patient satisfaction. Full article

Erythropoietin (EPO), the master regulator of erythropoiesis, is emerging as a pivotal mediator of brain repair. While its capacity to mitigate neural damage is well-documented, we posit that its most profound potential lies in actively orchestrating functional restoration. In the present review we summarize the molecular biology of EPO and the evidence establishing EPO as a potent modulator of neuroplasticity. We use an experimental strategy in which a specific behavioral task marks experience-activated neural circuits, and a subsequent, temporally precise administration of EPO provides a surge of plasticity-related proteins. This creates a synergistic interaction where the proteins are selectively captured by the activated synapses, directing plastic changes with high specificity. We present experimental evidence demonstrating that this synchronized protocol enables the recovery of spatial memory, reinstates synaptic plasticity, and activates genetic programs for plasticity in rodent models of brain injury. Furthermore, we show that endogenous EPO signaling is itself activity-dependent and integral to memory formation. This redefines EPO as a precision tool for neurorestoration, a potential now being pursued with engineered, non-erythropoietic variants of EPO in clinical trials for neurological and psychiatric disorders. Full article

Psychotic symptoms, including delusions and hallucinations, frequently complicate the course of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and frontotemporal dementia (FTD). Their presence accelerates decline, worsens outcomes, and complicates management. Cognitive screening in such patients is essential yet challenging due to attentional fluctuation, impaired insight, and diagnostic overlap. Addenbrooke’s Cognitive Examination III (ACE-III) is a multidomain tool with higher sensitivity than the MMSE. Evidence indicates that ACE-III captures disorder-specific cognitive-psychotic profiles: memory impairment in AD with delusions of theft, visuospatial and attentional deficits in DLB with hallucinations, or executive dysfunction in FTD with paranoid ideation. Mini-ACE (M-ACE), a shorter derivative, is useful in acute psychiatric or advanced dementia settings. This review synthesizes evidence on ACE-III and M-ACE in psychosis-related neurodegeneration, highlights their role in differentiating from primary psychiatric psychoses, and identifies knowledge gaps, particularly in atypical AD variants, mixed dementia, and autosomal dominant AD. ACE-III emerges as a practical and informative tool, but psychosis-specific normative data and longitudinal studies are needed. Full article

Now, half a century after the Vietnam War, Agent Orange exposure during the war is increasingly discussed as a risk factor for neurological diseases, particularly dementia and Alzheimer’s disease, among Korean and U.S. Vietnam War veterans. Emerging evidence supports associations between dioxin exposure originating from Agent Orange and alterations in brain morphology and function among Vietnamese residents, including children living in areas around former U.S. airbases exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after the Vietnam War. This paper summarizes what is known about the effects of Agent Orange exposure in the context of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, attention-deficit/hyperactivity disorder, and psychiatric disorders. Molecular biological studies have reported that TCDD may increase the risks of these neurological diseases by accelerating brain aging and inducing atypical neurodevelopment, partly mediated by the aryl hydrocarbon receptor. However, the effects of TCDD, which is a highly toxic contaminant of Agent Orange, as well as dioxin congeners other than TCDD, exhibit some inconsistencies. This review aims to provide new insights for mitigating the adverse neurological effects of dioxin exposure from Agent Orange, contributing to a healthier life for residents in Vietnam. Full article

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that impairs psychological functioning and increases susceptibility to various chronic illnesses, including inflammatory, metabolic, and cognitive disorders. Recent advances in neuroscience and microbiology have identified the brain–gut–microbiota axis as a key mediator of neuroimmune and neuroendocrine regulations, providing new insight into the pathophysiology of PTSD. This review synthesizes current findings from preclinical and clinical studies on gut microbiome alterations in PTSD, highlighting the underlying mechanistic pathways. Dysbiosis in PTSD is associated with immune dysregulation, altered neuroendocrine signaling, and neurotransmitter imbalances. Animal models, particularly those using the single prolonged stress paradigm, have demonstrated behavioral and microbial changes that mirror the characteristics of human PTSD. Human studies have revealed reduced abundance of beneficial bacterial taxa and increased inflammation-associated genera in patients with PTSD. Although emerging evidence supports the role of gut microbiota in PTSD, further research is needed to establish causal relationships and optimize microbiome-targeted therapies. Overall, the gut microbiome offers a novel and potentially modifiable target for the prevention and treatment of PTSD. Full article

Psychiatric disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), comprise a heterogenous group of severe mental illnesses (SMIs) characterized by disturbances in cognition, emotional regulation, or behavior. Cognitive impairment represents an accompanying feature of many SMIs, often interfering with or limiting essential daily life activities. SMIs arise from a complex interplay of genetic, epigenetic, developmental, and environmental factors that disrupt neural and cellular processes. SMIs often present with overlapping symptoms and sometimes co-occur, making misdiagnosis a common clinical challenge. To date, there is a lack of reliable and specific biological markers to aid in the differential diagnosis of cognitive impairment in SMIs and for distinguishing neurodegenerative dementias from SMIs with overlapping symptoms. In this context, blood-based biomarkers of the ATX(N) system associated with cognitive deficits in neurodegenerative diseases, such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid beta (Aβ), and tau proteins, may help to understand the biological basis of cognitive dysfunction in SMIs and support differential diagnosis. This narrative review summarizes the current evidence on the application of blood-based biomarkers of neurodegenerative dementias in SMIs and their association with the cognitive deficits observed in these conditions, as well as their relevance for differential diagnosis, disease monitoring, and the evaluation of treatment efficacy in psychiatric disorders. Full article

Background/Objectives: Evidence linking vitamins D and B₁₂ to psychiatric outcomes remains heterogeneous across designs, populations, phenotypes, exposures, and outcome formats. Methods: We conducted a PRISMA 2020 systematic review and exploratory meta-analysis of nutrient-specific status and supplementation evidence. PubMed/MEDLINE, APA PsycInfo, Cochrane Library, Google Scholar, ClinicalTrials.gov, and ProQuest were searched for human studies published in 2016–2025, with a final update on 1 March 2026. Forty-six studies were included (24 randomized controlled trials, 22 observational studies; N = 69,902), and 44 contributed quantitative data. Effects were harmonized to odds ratios (ORs) for cross-family comparability and pooled using Hartung–Knapp random-effects models; supplementation evidence was additionally interpreted on the standardized mean difference (SMD) scale. Results: Across the main evidence families, pooled estimates showed substantial heterogeneity and limited generalizability. Vitamin D supplementation showed an initial inverse estimate on the secondary harmonized OR scale (OR = 0.439, 95% CI 0.272–0.710) and a clinically interpretable SMD of −0.454 (95% CI −0.718 to −0.189), but heterogeneity was high (I² = 84.2%) and trim-and-fill attenuated the OR estimate to the null (OR = 0.88, 95% CI 0.48–1.63). Vitamin D status showed a similar pattern (primary OR = 0.615, 95% CI 0.424–0.890; trim-and-fill OR = 0.90, 95% CI 0.54–1.49). Vitamin B₁₂ status was inversely associated with outcomes (OR = 0.310, 95% CI 0.115–0.834), but heterogeneity was extreme (I² = 94.8%). B₁₂ supplementation evidence was sparse and null. Conclusions: The evidence supports targeted deficiency assessment, not routine supplementation. Full article

Background/Objectives: Alexithymia is a potential transdiagnostic risk factor for psychiatric and medical disorders involving affect dysregulation. But there is debate over whether a constricted imaginal capacity constitutes a core component of the construct or is a separable correlate. Our aim was to further explore this controversy as any revision to the construct has implications for clinical formulation, neurobiological models of associated default mode network dysfunction, and the coherence of the original psychiatric conceptualization. Methods: To replicate and extend previous factor analytic work, we conducted a two-stage exploratory factor analysis in a community sample that included individuals with a psychiatric history (N = 681). Using most of the subscale indicators employed in two prior factor analytic studies, we used a two-stage procedure: Stage 1 re-employed the general design of those studies. Stage 2 re-specified the analytic space by removing emotional reactivity and fantasizing-for-regulation variables that form their own separable latent dimensions. Results: Stage 1 yielded a conceptual replication of structural separation between alexithymia and imaginal processes. Stage 2 revealed meaningful cross-loadings obscured in the full set, most notably positive constructive daydreaming loading negatively on an externally oriented thinking factor, providing empirical support for the pensée opératoire construct. Additional cross-loadings linked dysphoric daydreaming and poor attentional control with negative emotion appraisal. Conclusions: The structural independence of alexithymia and imaginal processes is partly contingent on indicator set composition. Construct revision should be grounded not on two factor analytic studies using abbreviated self-report measures, but in convergent evidence across methods, including neuroimaging, electroencephalography, structured interview, performance-based assessment, and clinical observation. Full article

Paroxetine, a selective serotonin reuptake inhibitor commonly used to treat various psychiatric disorders, may adversely affect female reproductive function. Although apigenin has been shown to ameliorate reproductive abnormalities and ovarian dysfunction, its effect on paroxetine-induced reproductive toxicity in females remains unclear. Therefore, this study investigated the potential protective effects of apigenin against paroxetine-induced reproductive alterations in female rats. Female rats with regular estrous cycles were randomly assigned to four groups (n = 9 per group): control, apigenin, paroxetine, and paroxetine + apigenin. The rats received saline, apigenin (20 mg/kg), paroxetine (10 mg/kg), or their combination by oral gavage once daily for about 29 consecutive days. Compared with paroxetine treatment alone, apigenin co-administration restored decreased serum anti-Müllerian hormone (AMH) levels, enhanced PAS reactivity in the zona pellucida, reduced ovarian iNOS immunoreactivity, increased follicle and corpus luteum numbers, and increased ovarian VEGF immunoreactivity. However, apigenin administration alone was associated with reduced testosterone levels and alterations in certain ovarian and uterine histological features in female rats. In conclusion, the findings suggest that apigenin may ameliorate paroxetine-induced reproductive alterations in female rats by modulating AMH levels, follicle and corpus luteum numbers, and ovarian histochemical and molecular parameters. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, with a prevalence estimated at 4–20%. Among the conditions often co-occurring with PCOS are depressive and anxiety disorders. The aim of this study was to determine the prevalence of depressive and anxiety symptoms in women with PCOS. Methods: A literature search was conducted using PubMed/MEDLINE, Google Scholar, and Directory of Open Access Journals databases for studies published before May 2025. The analysis was conducted on a group of 5857 women (study group: 3610; control group: 2247) obtained from 35 studies, which met the inclusion criteria. Results: The prevalence of depressive symptoms in PCOS patients and the controls, according to the BDI, HADS-D, Mini-NPI and PHQ assessment tool, was 42.11% (95% CI: 32.6–52.2) vs. 13.62% (95% CI: 8.4–21.5; p < 0.001); 28.90% (95% CI: 20.7–38.8) vs. 15.80% (95% CI: 11.3–21.7; p = 0.010); 59.10% (95% CI: 30.9–82.4) vs. 65.90% (95% CI: 24.2–92.1; p = 0.792); and 26.50% (95% CI: 8.0–59.9) vs. 9.10% (95% CI: 1.8–35.1; p = 0.255). The prevalence of anxiety symptoms in the PCOS group and the control group, according to the HADS-A assessment tool, was 48.25% (95% CI: 36.1–60.6) vs. 31.40% (95% CI: 18.8–47.4; p = 0.098), respectively. Conclusions: The study confirms the higher prevalence of depressive symptoms in women with PCOS compared to the general population. These findings indicate the necessity of conducting psychiatric examinations and providing support for women with PCOS. Full article

Background: Poor mental health is prevalent among veterans who suffer from post-traumatic stress disorder (PTSD) and other psychiatric conditions. Canine-assisted interventions may improve psychological and social health in veterans. The parent study, a randomized controlled trial, revealed improvements in PTSD following both a service dog training program and an active control condition consisting of virtual dog training lessons. Thus, in the present post hoc secondary analysis, we analyzed both groups together (pooled arms) to examine gender-based differences in the effects of the altruistic service dog training programs on psychosocial outcomes. Methods: Veterans (N = 59) participated either in hands-on (with a dog and trainer) or virtual (no dog present) dog training programs over eight weeks and completed self-reported psychosocial measures before and after the program. Mixed-effect linear models were used to assess the interaction between time and gender on a series of psychosocial outcomes in the pooled sample. Results: The findings supported greater psychosocial improvements for female participants compared to male participants, including significant improvements in PTSD, perceived stress, and perceived physical health, and feeling greater closeness and lower avoidance in close relationships (ps < 0.05). The results revealed moderate to large effect sizes among female participants, suggesting meaningful clinical effects of the interventions (ds = 0.47–0.70). Conclusions: While the secondary analysis and small sample size limit causal inferences, the exploratory evidence suggests greater improvements in psychosocial health in female veterans after participating in the service dog training programs. Future research should tailor interventions to optimize the therapeutic effects for male and female veterans and identify other individual characteristics involved, such as combat exposure or post-traumatic stress symptom severity. Full article

Background: Inadequate management of emotional responses, limited access to emotion regulation strategies, and difficulties in emotion regulation may co-occur with alexithymic traits and interoceptive inaccuracy or confusion. These dimensions may influence lifetime eating disorder spectrum manifestations. Objective: To assess, in a general population sample without Axis I psychiatric disorders, alexithymic traits, interoceptive confusion/inaccuracy, and difficulties in emotion regulation, and to explore their associations with eating disorder spectrum manifestations. Method: In this cross-sectional observational study, fifty-two participants aged 18–30 years, recruited via a university bulletin board, were assessed online using the Toronto Alexithymia Scale (TAS-20), Interoceptive Accuracy Scale (IAS), Interoceptive Confusion Questionnaire (ICQ), Eating Attitude Test (EAT-26), and Difficulties in Emotion Regulation Scale (DERS) (protocol #01/2025). Results: Interoceptive confusion (ICQ) showed significant positive correlations with TAS-20, DERS, and EAT-26 total scores. ICQ scores were associated with TAS-20 subscales ‘difficulty identifying feelings’ (DIF) and ‘difficulty describing feelings’ (DDF). Participants with TAS-20 scores > 51 (n = 35; 67.3%) had significantly higher EAT-26 scores on ‘dieting’ (p = 0.043) and ‘bulimia’ (p = 0.017), as well as higher ICQ (p = 0.001) and DERS (p = 0.001) total scores, with smaller differences in the DERS ‘impulse’ subscale (p = 0.037). Conclusions: Preliminary findings suggest a pattern of co-occurring traits characterized by alexithymia, interoceptive confusion, emotional dysregulation, impulsivity, and eating disorder spectrum features, supporting the study hypothesis. Full article