A longer duration of untreated illness (DUI) has been associated with poorer outcomes across several mental disorders; however, few studies have investigated DUI in anxiety disorders, particularly in generalized anxiety disorder (GAD). This study aimed to identify sociodemographic and clinical factors associated with a longer DUI in GAD.

We conducted a cross-sectional, multicenter study, retrospectively reviewing the medical records of GAD patients from three mental health services. Sociodemographic and clinical variables were extracted for analysis. One-way analyses of variance and Pearson’s correlations were used to examine the relationship between DUI and categorical and quantitative variables, respectively. A multivariate linear regression model was then conducted to identify variables independently associated with DUI.

The total sample included 243 patients; the mean DUI was 30.92 (±65.25) months. In the final model, a longer DUI was associated with an earlier age at onset (B = −0.428; p = 0.023), a longer duration of illness (B = −0.431; p < 0.001), and the presence of multiple side effects (B = 55.778; p < 0.001). There was a trend toward statistical significance for the association between a longer DUI and multiple medical comorbidities (B = 13.122; p = 0.076).

Our findings suggest that reducing the time between the onset of GAD and the initiation of appropriate pharmacological treatment may improve clinical outcomes, mitigating the risk of a chronic course of illness. Further studies are needed to elucidate the role of DUI as a prognostic factor in GAD.

Adult major depression (MDD) studies implicate reward- and control-network dysconnectivity in suicidality, but it is unclear whether analogous alterations characterize adolescents, whose neural systems are still maturing.

Resting-state fMRI was obtained from 102 adolescents (12–17 years): 21 MDD with suicidal ideation (SI), 33 MDD without SI, and 48 matched healthy controls. Seed-based analyses targeted bilateral nucleus accumbens (NAc), ventral tegmental area (VTA), and bilateral dorsolateral prefrontal cortex (DLPFC).

Between-group effects were specific to NAc circuitry. Adolescents with SI showed reduced coupling of the left NAc with the left superior parietal lobule (BA7) versus controls, and diminished connectivity between the right NAc and right frontal pole (BA47) versus depressed peers without SI. No significant differences emerged for DLPFC- or VTA-seeded connectivity.

The identified functional dysconnectivities in reward-related circuits, particularly the FCs between the NAc and both the frontal pole and superior parietal lobule, may be implicated in the manifestation of suicidality among adolescents with MD. However, the lack of significant associations for DLPFC- and VTA-seeded FC in adolescent MDSI requires further elucidation.

We hypothesized that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and treatment currently U.S. Food and Drug Administration (FDA) approved to reduce worsening of kidney disease and kidney failure may protect against lithium-induced nephrotoxicity.

Renal adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) between December 2003 and December 2024 were analyzed using the validated OpenVigil 2.1 platform. Reporting odds ratios (RORs) were computed for the MedDRA terms renal impairment, renal failure, chronic kidney disease (CKD), end-stage renal disease (ESRD), and acute kidney injury (AKI) in association with lithium, semaglutide, and their co-reporting. A disproportionality signal was considered statistically significant when p < 0.05, and the lower bound of the information component (IC025) was greater than 0.

Lithium was associated with significantly elevated reporting odds across all renal AEs, with each outcome exceeding statistical signal thresholds (p < 0.0001, IC025 > 0). In contrast, semaglutide demonstrated inverse associations for renal impairment, renal failure, CKD, and ESRD (RORs = 0.25–0.54), and a neutral association for AKI (ROR = 0.96); however, none met the criteria for a disproportionality signal (IC025 < 0). Co-reported use of lithium and semaglutide did not yield a significant signal for any renal outcome, including AKI (ROR = 5.81, p = 0.015, IC025 < 0).

This observation, provides impetus to conduct adequate, thorough, mechanistic, clinical, and observational studies to determine whether semaglutide (and/or other incretin receptor agonists) could possibly mitigate the risk for, and/or modify the trajectory of, lithium-induced nephrotoxicity.

Acupuncture is a clinically recognized treatment for major depressive disorder (MDD), but the associations of efficacy with dosage, treatment course, frequency, acupuncture modality, needle retention time, and manipulation remain unclear. This study evaluated the efficacy and safety of acupuncture for MDD and explored potential moderating factors.

Randomized controlled trials of acupuncture for MDD were searched in CNKI, VIP Database, Wanfang Data, SinoMed, PubMed, Embase, Web of Science, and the Cochrane Library from inception to May 2025. Risk of bias was assessed using RoB 2, and certainty of evidence using GRADE. Data were analyzed in Stata 18.0.

36 trials involving 3843 participants were included. Compared with sham/placebo acupuncture, acupuncture showed greater antidepressant effects (SMD −1.12, 95% CI −1.57 to −0.67, P < 0.01). Very low-quality evidence suggested similar efficacy between acupuncture and antidepressants. Electroacupuncture was superior to manual acupuncture (SMD −0.24, 95% CI −0.42 to −0.07, P < 0.01). High- and moderate-dose acupuncture were more effective than low-dose regimens, and meta-regression suggested a linear dose-response relationship, with 30 sessions as the optimal dosage. Better outcomes were associated with treatment course >6 wk, 3 times weekly, needle retention time of 20–30 minutes, and electroacupuncture. No significant difference was found between needle manipulation and non-manipulation.

Acupuncture significantly alleviates depressive symptoms in MDD. Efficacy appears to be influenced by dosage, acupuncture modality, treatment course, frequency, and needle retention time, with 30 sessions, treatment course > 6 wk, 3 sessions weekly, 20–30 minutes retention, and electroacupuncture showing the most favorable outcomes.

Fibromyalgia (FM) is a heterogeneous chronic pain condition frequently accompanied by psychiatric symptoms. Although affective symptoms are highly prevalent, they are often treated as secondary correlates of pain or disability. This study examined whether psychiatric symptom profiles parallel disability severity or represent partially independent dimensions across disability-based FM phenotypes.

We analyzed a harmonized multisite cohort of adults with FM recruited from two academic medical centers. Disability-based phenotypes were defined using a validated percentile-based classification dichotomizing participants into low-impact and high-impact FM. Psychiatric domains were derived from standardized measures of depressive and anxiety-related symptoms. Multivariate clustering was used to identify affective profiles, and their distribution across disability phenotypes was examined. Dimensional analyses assessed the relationship between affective burden and functional impairment.

Among participants with complete psychiatric data (n = 613), four reproducible affective profiles were identified: minimal affective symptoms, mild affective symptoms, moderate mixed affective symptoms, and severe mixed affective symptoms. Although profiles characterized by greater affective burden were enriched among individuals with high-impact FM, all affective profiles were represented across both disability groups. Notably, a substantial proportion of individuals with high-impact FM exhibited minimal or mild affective symptoms. Dimensional analyses supported partial orthogonality between affective burden and disability severity.

Psychiatric comorbidity in FM does not simply reflect pain severity or functional impairment. Instead, affective symptoms form partially independent dimensions that cut across disability-based phenotypes. These findings support a multidimensional neuropsychiatric framework for FM with implications for stratified assessment and personalized intervention.

Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants. Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear. We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for anhedonia.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched Ovid Embase/MEDLINE/PsycINFO, Cochrane Library, Scopus, Web of Science, and Google Scholar. Eligible studies included adults with MDD receiving ketamine or esketamine and undergoing fMRI, PET, or related imaging during rest or reward/emotion tasks. Thirteen studies met inclusion criteria (N = 623; 482 MDD/TRD, 141 controls), mostly randomized, double-blind, and placebo-controlled; no eligible esketamine neuroimaging studies were identified.

Intravenous ketamine (typically 0.5 mg/kg over 40 min) was associated with short-term modulation of fronto-striatal and limbic networks. Resting-state fMRI commonly showed altered ventral striatal–prefrontal/ACC connectivity and broader DMN/salience/executive network reorganization across acute-to-subacute windows (≈2–48 h), with some effects changing at later follow-up (≈10 days). Task-based fMRI showed altered ventral striatal/putaminal responses during reward anticipation/feedback and modulation of medial prefrontal/cingulate activity during emotion processing. PET findings suggested increased prefrontal–cingulate metabolism and region-specific 5-HT₁B binding/availability changes, with baseline ventral striatal 5-HT₁B measures associated with symptom profiles and symptom change.

Ketamine is associated with rapid reconfiguration of reward-related circuitry, but few studies directly measured anhedonia; findings likely reflect broader reward-processing and antidepressant-associated mechanisms. Larger longitudinal multimodal studies are needed to validate biomarkers and durability.

The present study investigated the management of predominant negative symptoms in hospitalized patients and assess the impact of targeted pharmacological and psychological interventions.

This longitudinal, prospective, multicenter cohort study was conducted across multiple hospitals in Slovakia, focusing on inpatients, with assessments at admission and discharge. Eligible participants were hospitalized adults (18–65) diagnosed with schizophrenia and predominant negative symptoms. Treatment effectiveness was measured using the modified Short Assessment of Negative Domain, Self-evaluation of Negative Symptoms, Personal and Social Performance, and Clinical Global Impression scales. Means changes and effect sizes were calculated from baseline to final assessment. Differences in the perception of negative symptoms between patients and doctors were examined.

At discharge, patients showed significant improvements in symptom severity and functioning on all scales. Primary and secondary negative symptoms significantly decreased, especially those linked to positive and affective symptoms. Functioning improved, with fewer severe impairments in daily life. Most patients were on antipsychotic polytherapy throughout hospitalization, with around 85% receiving multiple antipsychotics at admission and at discharge. Non-pharmacological interventions were also widely used, with nearly nine out of ten patients receiving at least one such therapy during hospitalization.

Negative symptoms in schizophrenia pose a major treatment challenge, leading to functional impairment and poor quality of life. While positive symptoms often trigger hospitalizations, negative symptoms have a lasting impact on prognosis. Results suggest both D3-receptor–targeted pharmacotherapy, particularly cariprazine, and integrated non-pharmacological interventions may contribute to meaningful improvements in negative symptoms during hospital care.

Panic disorder (PD) is a psychopathological condition characterized by short-lived anxiety attacks in association with several physical symptoms, followed by the fear of other attacks’ possible occurrence or their consequences and avoidance behaviors. Recent literature highlighted a significant correlation between autism spectrum disorder (ASD) and anxiety disorder. To date, the specific association between PD and autistic traits (ATs) remains to be clarified. This study aimed to investigate the presence of an autism spectrum in patients with PD, specifically focusing on the presence of possible factors associated with these conditions.

The study recruited 112 subjects: 55 subjects with a clinical diagnosis of PD and 57 healthy controls (HCs). All participants were evaluated with the Panic Agoraphobic Spectrum—Short Version (PAS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum) questionnaire.

Results outlined a significant correlation between agoraphobic-panic symptoms and autism spectrum, with significantly positive correlations of all AdAS Spectrum domain scores, as well as its total score with all PAS-SV domains as well as with its total score. Moreover, atypical panic symptoms, and anxious expectation, and maladaptive behaviors were factors associated with a possible underlying presence of higher AT in PD subjects.

Our findings support the association between the panic-agoraphobic dimension and ASD. Indeed, increased reactions to stressful life events due to autistic altered sensory reactivity may increase fears responses such as anxious manifestations and maladaptive behaviors.

Functional neurological symptoms that do not meet clinical definitions of functional neurological disorder (FND) are common in clinical practice. Understanding the distinction between these “benign” functional symptoms and FND is crucial in defining FND as an entity for study and a clinical syndrome. We aimed to measure the frequency of functional symptoms in people who do not have FND.

A survey was administered to 95 clinicians who attended an international conference on FND. Participants were asked to report the occurrence and characteristics of experiences with features of functional sensory or motor symptoms, or dissociation, which they had experienced at any time.

Of the 95 people who responded to the survey, 57.4% reported having experienced any functional symptoms, and 47.9% reported having experienced functional motor or sensory symptoms. The symptoms reported were generally short-lived and caused only mild distress and disruption. Most respondents who reported having experienced a functional symptom reported having had multiple events through their lives.

The results suggest that the lifetime occurrence of functional neurological symptoms is at least an order of magnitude higher than FND. The high prevalence of functional symptoms in people who have never had FND challenges the assumption that the occurrence of functional neurological symptoms is synonymous with FND. We propose that FND is better conceived of as a failure of the mechanisms by which functional neurological symptoms resolve, rather than the occurrence of functional symptoms per se. This reconceptualization implies new research directions for the underlying etiology of FND.

Autistic traits (ATs) are associated with difficulties in social functioning, but their impact on the quantity and the quality of daily-life social interactions is not yet fully understood. Hereby, we examined the relationship between AT and daily-life social interactions in adolescents and young adults.

Data were derived from the TwinssCan cohort (N = 593). ATs were assessed using the Autism Spectrum Quotient (AQ), while the quantity and the quality of daily-life social interactions were evaluated using the Experience Sampling Methodology. Multilevel regressions were performed, with the AQ as the independent variable and each social/solitary quantity/quality variable as the dependent variable. Models were adjusted for age, sex, and general psychopathology, measured with the Symptom Checklist-90.

No significant association was found between AQ total scores and quantity of social interactions. However, AQ total scores were significantly associated with quality of social interactions. Higher ATs were associated with an increased preference to be alone (B = 0.04, 95% CI 0.01–0.07), less pleasure while in-company (B = −0.02, 95% CI −0.04 to −0.01), less feeling of safety while in-company (B = −0.02, 95% CI −0.04 to −0.002), and less feeling of belongingness (B = −0.02, 95% CI −0.03 to −0.001). ATs were differently associated with the quality of social interactions depending on the familiarity. No significant associations were found between ATs and solitary qualities.

Our findings highlight the importance of evaluating ATs during clinical assessments, especially in adolescents and young adults, to evaluate the impact on social interactions and the potential psychopathological consequences.

Resting-state networks (RSNs) consist of coherent spontaneous activity patterns that support a wide range of sensorimotor and higher-order cognitive functions. In schizophrenia (SZ), RSN alterations reflect disruptions in the brain’s functional architecture. Given the heterogeneity of SZ, accurate spatial mapping of RSNs at the individual level is crucial for characterizing altered brain connectivity in a more personalized manner. To achieve this, we used single-subject independent component analysis (ICA) to extract RSNs at the individual level, preserving unique functional patterns and accounting for variability among SZ patients.

We analyzed a resting-state functional magnetic resonance imaging dataset from 74 SZ patients and 74 matched healthy controls (HCs) obtained from the publicly available COINS database. Using single-subject ICA, we extracted 14 distinct RSNs associated with sensory, motor, and higher-order cognitive functions. Voxel-wise statistical comparisons were performed to identify spatial differences between the groups.

The SZ group exhibited widespread RSN alterations in regions associated with visual, motor, and cognitive processing. Significant spatial differences were observed within each network, with the most extensive changes occurring in the somatomotor network and three cognitive networks: the cingulo-insular, medial prefrontal, and left frontoparietal networks. Within the default mode network, differences between SZ patients and HC were observed exclusively in visual areas.

Single-subject ICA provides a valuable approach for investigating RSN alterations in SZ and enables a detailed, individualized characterization of functional connectivity disruptions. The extensive connectivity alterations in visual, motor, and cognitive networks highlight the complex interplay among these systems in SZ.

It is unclear whether patients with obsessive-compulsive disorder (OCD) and expert clinicians agree on the symptoms’ qualities that are essential for a diagnosis of OCD. This study examined whether OCD patients and expert clinicians agree on the essential characteristics for an OCD diagnosis. It compared the endorsement rates of various descriptive terms and assessed whether response profiles could predict group membership (patients versus expert clinicians).

Sixty-four OCD patients and 36 OCD expert clinicians answered a questionnaire on their views regarding the defining characteristics of OCD symptoms. It included a compilation of adjectives extracted from DSM-5 to describe disorders in the compulsive–impulsive spectrum. Chi-square tests compared response prevalence between groups and binary regression identified distinguishing features. The significance level was set at 0.05.

All descriptors differed significantly between OCD patients and expert clinicians (p < 0.01), with clinicians consistently endorsing more items as applicable or essential. Although the logistic regression model significantly distinguished the 2 groups and showed high explanatory power (R2 = 0.7) with 99% classification accuracy, no individual descriptors were significant predictors.

There is a mismatch between clinician-defined diagnostic language and patients’ subjective experience of OCD, including core symptom descriptors. This gap suggests that current OCD diagnostic construct may not fully capture how patients perceive their condition, potentially limiting its validity and clinical utility. Adopting more patient-centered language could improve assessment, psychoeducation, and treatment engagement.

A mutual influence between mood disorders and obesity has been reported. Maladapting eating behaviors associated with mood spectrum swings may play a pivotal role in the development and maintenance of obesity. Considering that, the aim of the present study is to investigate the relationship between problematic eating behaviors, namely emotional eating, grazing and night eating, with impulsivity and lifetime mood spectrum (mood, energy, cognition, rhythmicity and vegetative functions) in severe obese patients seeking bariatric surgery.

304 obese outpatients were recruited at the Psychiatric Unit of the University Hospital of Pisa. Participants completed psychometric tools including the Emotional Eating Scale (EES), the Italian-Night Eating Questionnaire (I-NEQ), the Grazing Questionnaire (GRAZ), the Barratt Impulsiveness Scale (BIS-11), and the Mood Spectrum Self-Report – lifetime version (MOODS-SR). Descriptive analyses and linear correlation were performed.

The sample was predominantly female (71.4%), with a mean age of 47.5 ± 10.9 years and a mean BMI of 43.3 ± 6.3 kg/m2. Impulsivity was positively correlated with depressive and manic mood, energy, and cognitive MOODS-SR domains. Emotional eating, night eating, and grazing were significantly associated with the MOODS-SR total score (r=0.422, p=0.000; r=0.321, p=0.001; r=0.321, p=0.000, respectively) and with specific depressive and manic subdomains of the MOODS-SR.

Loss-of-control eating behaviors were positively associated with lifetime depressive and manic mood spectrum features in bariatric patients, highlighting the importance of assessing these dimensions to promote a tailored and integrated treatment.