Journal of Affective Disorders Reports

Background: Substance use is common among individuals with depression. Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but current clinical guidelines have discouraged TMS treatment for individuals with depression and co-occurring substance use given concerns for limited efficacy. However, limited data exists on whether substance use affects response to TMS. Methods: Using electronic health record data from patients who received a standard course of TMS for major depressive disorder at an academic medical center, we investigated associations between substance use frequency and response to TMS, defined as change in Patient Health Questionnaire-9 (PHQ-9) scores. Substance use frequency was extracted for alcohol, cannabis, nicotine, stimulants, benzodiazepines, opioids, inhalants, psychedelics, and other drugs. We performed ANCOVA and multiple regression analyses to predict change in PHQ-9 score based on substance use frequency, controlling for pre-TMS PHQ-9 score, age, sex, and number of TMS sessions received. Results: We extracted data from 219 TMS courses. Alcohol was the substance used most commonly (34.2%), followed by prescription benzodiazepines (28.3%), and prescription stimulants (21.0%). Across all substance categories, substance use was not associated with change in PHQ-9 score (all p > 0.05, Cohens d=0.00 to 0.30). In multiple regression models to compare individual levels of substance use frequency (e.g., daily use vs. no use), level of substance use was not associated with change in PHQ-9 score (all p > 0.05). The range of plausible effects of substance use frequency on PHQ-9 change was generally below the minimal clinically important difference for PHQ-9, suggesting substance use was unlikely to have a meaningful clinical effect on antidepressant response to TMS. Conclusions: Low to moderate substance use does not have a clinically significant effect on antidepressant response to TMS. Low-level substance use should not exclude individuals with depression from receiving TMS.

Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.

Purpose: There is a long-standing perception that individuals who stutter are less intelligent, with the disfluencies unique to stuttered speech often assumed to be the overt reflection of lower intelligence, despite no supporting evidence. The purpose of the present study was to explore the validity of this assumption by examining the cognitive abilities of adults who stutter compared to the general population using the NIH Toolbox (C) Cognition Battery (NIHTB-CB). Method: Sixty-three adults who stutter completed the NIHTB-CB, which includes seven standardized measures assessing crystallized cognition (Picture Vocabulary, Oral Reading) and fluid cognition (List Sorting Memory Test, Pattern Comparison Processing Speed Test, Flanker Inhibitory Control Test, Dimensional Change Card Sort Test, Picture Sequence Memory Test). The NIHTB-CB generates t-scores adjusted for demographic variables based on a large sample of neurotypical adults. Results: Composite scores of overall cognition for adults who stutter were not statistically equivalent, rather, their scores were higher than the general population. Higher scores were driven by crystallized cognition, with significantly higher scores on Oral Reading subscale. Conclusions: Present findings demonstrate that adults who stutter possess cognitive skills that are comparable to or potentially higher, than the general population. These results challenge the misconception that stuttering reflects diminished intelligence and offer evidence to mitigate stereotype threat.

Aim: The Patient Safety Screener-3 (PSS-3) is a brief suicide-risk screening tool. Item 1 of this scale assesses depressive mood but is not included in the total score. We examined the association of item 1 with depressive symptom severity and characterized the suicide-related risk captured by PSS-3 total positivity. Methods: We conducted a nationwide cross-sectional survey among resident physicians in Japan. Associations between PSS-3 item 1 endorsement and Patient Health Questionnaire-9 (PHQ-9) scores were evaluated using the Wilcoxon rank-sum test. Diagnostic performance of item 1 was evaluated using PHQ-9 positivity ([&ge;]10) as reference standard. We also compared Short-form Scale for Suicide Ideation (SIS-6) scores according to PSS-3 total positivity and PHQ-9 item 9 positivity. Results: A total of 1,844 participants were included. PSS-3 item 1 was endorsed by 443 physicians (24.0%), and 47 (2.5%) met the criteria for PSS-3 total positivity. Item 1 showed 79.3% sensitivity and 79.5% specificity for PHQ-9 positivity. SIS-6 scores were higher in the PSS-3 total-positive group than in the total-negative group (median [IQR], 6 [5-9] vs 0 [0-1]; p<0.001). The SIS-6 showed a higher area under the receiver operating characteristic curve (AUC) and Youden index using PSS-3 total positivity (AUC, 0.961; optimal cutoff, 3) than PHQ-9 item 9 positivity (AUC, 0.907; optimal cutoff, 2). Discussion: PSS-3 may support brief, simultaneous screening for depressive symptoms and suicide-related risk. Compared with PHQ-9 item 9, PSS-3 may capture a more severe spectrum of suicide-related risk. PSS-3 may facilitate identification of individuals requiring further mental health assessment.

Introduction: Functional Neurological Disorder (FND) affects women approximately three times more often than men. This disparity has largely been attributed to higher trauma prevalence and diagnostic bias, while the potential contribution of hormonal influences has received little attention. Methods: An online questionnaire was distributed through FND clinics in thirteen countries, assessing self-reported symptom change across five hormonal events: hormonal contraception, pregnancy, the menstrual cycle, menopause, and gender-affirming hormone therapy. Eligible participants were cisgender women with a diagnosis of FND, or gender minority individuals (transgender or non-binary). Perceived symptom change was rated on a five-point scale ranging from large improvement to large worsening. Results: Among 262 respondents (96% female; mean age 39 years), several hormonal contexts were associated with self-reported symptom changes. Overall, hormonal contraception and pregnancy were frequently associated with worsening of motor and cognitive symptoms, and menopause with worsening across all symptom domains. Menstrual cycle analysis revealed a phase-dependent pattern: worsening was most frequently reported during menstruation and the luteal phase, whereas improvement was most frequent during the follicular phase. Reported changes were not uniform, with a substantial proportion of participants describing no change or improvement. Conclusion: Self-reported FND symptom severity appears to vary with hormonal context, with motor and cognitive symptoms most consistently affected. Given the retrospective, self-report design, these findings are hypothesis-generating and support prospective research into the role of hormonal transitions in FND.

Cognitive deficits in depression often persist despite pharmacological and psychotherapeutic treatment. Existing cognitive retraining programs are typically time- and resource-intensive, and place limited emphasis on addressing subjectively perceived cognitive difficulties or generalization of gains. This proof-of-concept study aimed to adapt the Integrated Cognitive Control Training (ICCT) into a brief format for patients with depression and to generate preliminary evidence of feasibility and effectiveness. The intervention was adapted into a manualized five-session program through a literature review, expert surveys involving clinicians and individuals with lived experience of depression, and a trial run. The study followed a single-group, open-label pre-post design (N = 16). Significant improvements were observed in cognitive flexibility (Color Trails Test-2: t = 3.52, p = 0.003, d = 0.88), depression severity (Montgomery-[A]sberg Depression Rating Scale: t = 6.66, p < 0.001, d = 1.67), and subjective cognition (Perceived Deficits Questionnaire: t = 5.06, p < 0.001, d = 1.3). The intervention demonstrated high acceptability and demand. These findings suggest that the Brief ICCT is a feasible and potentially effective approach for addressing cognitive deficits, with improvements extending to depressive symptom severity and socio-occupational functioning. These proof-of-concept findings justify further evaluation of Brief ICCT in adequately powered randomized controlled trials.

Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are prevalent, chronic, and disabling mental health conditions which are difficult to treat. Ketamine has demonstrated effect for improving depression and PTSD symptoms independently but reports often overlook focused comorbid improvement of these symptoms within individuals. To address this, we assessed blood-based biomarker and psychological changes following low-dose oral ketamine treatment for adults with MDD alone (n=14) and comorbid MDD+PTSD (n=21). Before treatment, the MDD clinical group presented with more severe depression, lower serotonin levels and higher kynurenine levels than the MDD+PTSD group. Post-treatment there were no detectable differences in the biological response between clinical groups, with combined analysis revealing common decreases in circulating brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF-A). Additionally, post-treatment, both clinical groups showed improvements in anxiety, stress, social functioning, suicidal ideation, and general well-being measures, as well as individual improvements in depression scores and PTSD symptoms in the MDD- and PTSD-containing groups, respectively. Collectively, this study presents additional evidence that low-dose oral ketamine treatment can be effective for MDD and MDD+PTSD, individually and comorbidly, and that both MDD and PTSD clinical groups responded in the same biological manner.

Background: Personality traits are consistently associated with bipolar disorder (BD). However, their features across BD diagnostic subtypes and their modulation by demographic and health-related factors remain largely unexplored. This study aimed to characterize Big Five personality domains in individuals with BD compared to controls, and to examine differences between BD type I (BD-I) and BD type II (BD-II). Methods: We analyzed 833 participants from the MadManic cohort (300 BD subjects and 533 controls) with available Big Five Inventory-2 (BFI-2) data. Linear regression models were used to assess associations between personality traits and BD diagnosis, adjusting for relevant covariates. Additional comparisons were conducted across sex, age, and Body Mass Index (BMI), and between BD-I and BD-II patients. Results: BD was associated with higher Negative Emotionality (NE) and lower Extraversion and Conscientiousness. Conscientiousness was also inversely associated with BMI. Within the BD group, individuals with BD-I exhibited lower NE compared to those with BD-II. Stratified analyses indicated that elevated NE in BD was the most consistent domain across sex, age, and BMI subgroups, whereas differences in Extraversion and Conscientiousness varied depending on subgroup features. Conclusions: BD is characterized by a distinct personality profile marked by elevated NE and reduced Extraversion and Conscientiousness. NE emerged as the most robust domain associated with BD, which may also differentiate between subtypes, with higher levels observed in BD-II than BD-I. These findings highlight the relevance for considering demographic and health-related factors, particularly BMI, when interpreting personality patterns in BD, supporting the role of personality dimensions to examine clinical heterogeneity.

Objective: Disruption of the excitation/inhibition balance may contribute to the pathophysiology of bipolar disorder, with post-mortem studies reporting abnormalities in GABA-receptors, interneurons and inhibitory signaling in prefrontal areas. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) enables in vivo assessment of cortical excitability/inhibition. This study examined short-latency intracortical inhibition (SICI) after left- and right-dorsolateral prefrontal cortex (DLPFC) stimulation in bipolar depression (BDep, n=10) and healthy controls (HC, n=22). Methods: SICI (paired-pulse TMS) and excitability (single-pulse TMS) were quantified using local- and global-mean-field-power. Associations with lithium use and between-group differences in TMS-evoked potential amplitudes were also explored. Results: For left-DLPFC stimulation, BDep showed weaker SICI than HC (local: 3.7%{+/-}12.5 vs 9.0%{+/-}20.3, p=0.05; global: 1.5%{+/-}11.7 vs 8.8%{+/-}20.6, p=0.10), driven by larger ppTMS responses (weaker inhibition). For right-DLPFC stimulation, BDep showed stronger SICI than HC (local: 17.3%{+/-}16.1 vs 0.75%{+/-}27.1, p=0.36; global: 16.2%{+/-}14.6 vs -1.0%{+/-}21.8, p=0.03), driven by a larger spTMS response (enlarged excitability). Stronger right-hemispheric global-SICI was most pronounced in BDep patients not using lithium (17.9%{+/-}7.0) vs lithium users (3.9%{+/-}11.9) and HC (pFDR=0.03). Conclusions: BDep is characterized by reduced cortical inhibition after left DLPFC stimulation and enlarged cortical excitability after right DLPFC stimulation; the latter partly normalized by lithium. Significance: To our knowledge, this is the first study to apply TMS-EEG to the bilateral DLPFC in BDep, revealing distinct patterns of hemispheric dysfunction. These findings warrant replication in larger samples, to further elucidate the underlying pathophysiology and inform the mechanisms of action of neuromodulation treatments, such as rTMS.

Ayahuasca use has expanded beyond its traditional Amazonian contexts, yet prospective longitudinal data examining depressive symptoms following naturalistic use in the United States remain limited. We conducted an interim analysis of an ongoing prospective observational cohort of adults participating in naturalistic ayahuasca use in Las Vegas, Nevada. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with higher scores indicating greater depressive symptom severity, at baseline and approximately 48 hours, 30 days, 60 days, and 90 days following exposure. At interim analysis, PHQ-9 data were available for 87 participants at baseline, 61 at 48 hours, 41 at 30 days, 33 at 60 days, and 26 at 90 days. Mean PHQ-9 scores decreased from 8.06 (SD 5.96) at baseline to 4.39 at 48 hours, 3.76 at 30 days, 3.97 at 60 days, and 3.65 at 90 days. Among participants with matched baseline and follow-up assessments, mean changes were -3.58 points at 48 hours, -4.47 at 30 days, -4.48 at 60 days, and -4.76 at 90 days. In a mixed-effects model accounting for repeated observations, PHQ-9 scores remained significantly lower than baseline at 48 hours ({beta}=-3.70; 95% CI -5.09 to -2.31), 30 days ({beta}=-4.34; 95% CI -6.01 to -2.67), 60 days ({beta}=-3.97; 95% CI -5.77 to -2.18), and 90 days ({beta}=-4.25; 95% CI -6.18 to -2.33; all p<0.001). Among participants with baseline PHQ-9 scores [&ge;]5 and matched follow-up data, 69.2% demonstrated a reduction of at least 5 points at 90 days. These interim findings provide preliminary evidence of a sustained longitudinal association between naturalistic ayahuasca exposure and lower depressive symptom scores through 90 days in a U.S.-based cohort. The observational design, self-selection, incomplete follow-up, and absence of a control group preclude causal inference. Continued longitudinal follow-up is needed to determine the durability of this association.

Background Floods are among the most devastating natural disasters worldwide and are increasingly associated with adverse mental health outcomes, particularly Post-Traumatic Stress Disorder (PTSD). In December 2023, Hanang District in northern Tanzania experienced catastrophic mud floods that resulted in extensive loss of life, destruction of property, displacement of households, and disruption of livelihoods. While emergency humanitarian responses focused primarily on physical needs, limited evidence exists regarding the long-term psychological consequences among survivors. Therefore, this study aimed to determine the patterns of PTSD manifestations and assess cognitive factors associated with PTSD symptoms among flood victims in Hanang District, Tanzania. Methods A community-based cross-sectional study was conducted among 360 flood victims one year after the disaster. PTSD symptoms were assessed using the PTSD Checklist for DSM-5 (PCL-5). Descriptive statistics summarized PTSD severity, while chi-square tests and regression analyses examined associations between socio-demographic characteristics and PTSD manifestations. Cognitive factors were assessed based on participants' exposure to traumatic experiences and perceptions of traumatic events. Results The mean PCL-5 score was 39.2 (SD = 20.6), indicating a high burden of psychological distress. Approximately 45% of respondents had severe PTSD symptoms (PCL-5 [&ge;]45), while another substantial proportion demonstrated moderate symptom severity. PTSD manifestations varied significantly by geographical location (p < 0.001), household income (p = 0.011), and marital status (p = 0.002). Age positively predicted PTSD severity ({beta} = 0.019, p = 0.001), whereas household income negatively predicted symptom severity ({beta} = -0.297, p = 0.001). Exposure to natural disasters constituted the predominant cognitive factor, with 45% directly experiencing the flood and 38.3% witnessing the event. Exposure to secondary traumatic experiences through witnessing or learning about violent events was also common. Cognitive trauma exposure demonstrated a significant association with PTSD symptoms ({chi}2, p < 0.001). Conclusion PTSD remains highly prevalent among flood survivors in Hanang district. Both direct and indirect trauma exposure significantly contributed to PTSD manifestations. Comprehensive disaster recovery programmes should integrate trauma-focused psychological services, cognitive behavioural interventions, routine PTSD screening, and community-based psychosocial support alongside socioeconomic recovery initiatives.

Oregon (OR) and Colorado (CO) were the first states to enact regulations for provision of psilocybin with support of licensed "facilitators." As more states and countries adopt similar policies, informed public policy decisions require that client characteristics and rationale for using psilocybin, psilocybin dosing practices, mental health outcomes, and adverse events are understood. We performed a retrospective observational study of responses for 2363 individuals receiving psilocybin at OR and CO regulated service centers. Clients and facilitators entered data before and after receiving psilocybin, including the Mystical Experience Questionnaire-30 (MEQ-30), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and World Health Organization Well-Being Index-5 (WHO-5). Preexisting mental health issues were common (66%) in participants. Psilocybin doses ranged from 1-95 mg, with a mean total of 28*8 mg. We observed improvements of 49% in PHQ-9 scores, 51% in GAD-7 scores, and 22% in WHO-5 scores at two-weeks after dosing. MEQ-30 scores were dose-dependent. Changes in PHQ-9 and GAD-7 scores were not different for psilocybin doses [&le;]30 mg and >30 mg, and only weakly correlated with MEQ-30 scores. There were 94 mild adverse events during and after dosing, five more serious events not clearly related to treatment, and evidence of possible risk of increased suicidality. Study limitations include open label administration, self-reporting, loss of participants for follow-up, and a short 2-week post-dosing end-point. We conclude that psilocybin services, delivered within these regulated frameworks, is associated with improvements in mental health in real world populations, however, more robust monitoring is needed to ensure safety.

Autistic individuals may be at an increased risk of hazardous drinking compared to non-autistic counterparts: potential motivations include facilitated social interactions and self-medication of co-occurring difficulties, and possible risk factors include being older and female. However, research remains limited and centred around clinical samples. Given the diversity of the autistic community, it is important to understand the intricacies of alcohol use to inform appropriate support. Eighteen autistic adults took part in semi-structured interviews about their drinking experiences. Data were analysed using reflexive thematic analysis. Three main themes were created (Autistic experiences, Managing expectations and coping by drinking and Recommendations for support). Autistic experiences was used to denote the ways in which participants described their own autistic features influenced their relationship with alcohol. Managing expectations and coping by drinking was chosen to reflect the pressures felt by participants to show up in social relationships and the co-occurring difficulties many of them managed using alcohol. Therapeutic preferences for alcohol services were captured under Recommendations for support. As expected, participants used alcohol to facilitate social interactions and self-medicate. However, additional nuances uncovered may provide clinical utility and highlight the need for further research in other demographics within the community.

Abstract: Objective: Post-traumatic epilepsy (PTE) is a common sequela of traumatic brain injury (TBI). Research indicates that individuals with PTE tend to experience greater cognitive difficulties compared to those with TBI alone. However, it is plausible that a distinct cognitive profile exists that distinguishes between TBI cases with and without PTE. We aimed to identify longitudinal changes in cognitive measures among TBI patients to better assess the changes associated with developing PTE. Setting: Outpatient. Participants: Prospective subjects who had suffered TBI within 6 months post-injury (TBI-6M, n=32), retrospective subjects with pre-existing PTE diagnoses (PTE, n=20), and healthy control subjects (HC, n=41). Design: We examined cognitive performance for TBI patients within 6 months post-injury, then again within 12 months (TBI-12M, n=26), and within 18-months (TBI-18M, n=25), and compared this with cognitive performance among HC and PTE. Main Measures: Cognitive tests administered yielded 15 test components for analysis. We utilized linear mixed effects modeling to examine cohort-level differences cognitive function. Results: 11/15 tests showed a significant performance deficit in the PTE subjects compared to HC. TBI-6M was not significantly different from the PTE subjects; with time, 9/15 tests showed some degree of recovery in TBI subjects. Tests for information processing speed/working memory and executive function showed strong recovery (TBI-6M vs. TBI-18M, SDMT written: p<0.0001, SDMT oral and COWAT: p<0.001). Tests for visual attention/working memory also showed a smaller but significant recovery (TBI-18M vs. PTE, p<0.05). By contrast, tests for verbal memory [HVLT-R Delayed Recall] showed chronic impairment in TBI (TBI-18M vs HC, p<0.0001). TBI subjects generally trend towards recovery in cognitive performance post-TBI. Conclusions: Information processing speed/working memory are strong indicators for TBI recovery, while auditory learning/memory shows chronic impairment. The stagnation of recovery in cognitive domains typically characterized by robust recovery may correlate with an elevated risk of developing PTE.

Background: Bipolar disorder is associated with persistent social, cognitive, and functional impairment during euthymia, yet the neural mechanisms underlying these deficits remain unclear. Alterations to self-referential processing are a candidate mechanism, but existing electrophysiological studies rely on emotionally valenced paradigms that potentially confound self-processing with emotional biases. Methods: We analysed electroencephalography from 28 patients with bipolar disorder (type I or II) and 28 age- and sex-matched healthy controls during an emotionally neutral colour judgment task with self-related (preference) and non-self-related (similarity) conditions. Late positive potentials, temporal generalisation decoding, and frequency band decoding (theta, alpha, beta) were used to characterise the temporal dynamics and oscillatory correlates of self versus non-self processing. Results: Controls showed higher overall event-related potential amplitudes and greater self versus non-self differentiation than patients (condition by group interaction, 337 to 946 ms). Broadband temporal generalisation decoding revealed extensive cross-temporal generalisation of the self versus non-self representation in controls, spanning most of the trial, but no significant generalisation in patients. Frequency analyses showed that alpha and beta carried self versus non-self information in both groups, with broader extent in controls, and that anterior theta carried this information in patients but not controls. Exploratory correlations linked decoding measures to rumination and anxiety but not to manic symptoms. Conclusions: The neural representation distinguishing self-referential from externally guided processing was both smaller in amplitude and less temporally sustained in bipolar disorder. Reduced persistence is not detectable by conventional amplitude analyses, and may bear on the self-related and social cognitive difficulties reported in this population.

Introduction: In 2020, Oregon became the first US state to legalize state-regulated psilocybin services. This study aims to examine: 1) the clinical and demographic characteristics, 2) psilocybin use motivations, and 3) differences in preparedness among patients seeking care in a Oregon- based pilot consult service specializing in psilocybin risk reduction. Methods: This retrospective chart review abstracted sociodemographics, trauma history, and medical and psychiatric risks of patients (November 2023 - September 2025). The Psychedelic Preparedness Scale (PPS), a validated self-report questionnaire, measured preparedness. Two sample t-tests examined associations of PPS scores by insurance, consult motivations, and prior psychedelic use. Results: Patients (N=29) had a mean age of 47.14 years (SD=15.9), were majority female (55.2%); White (82.8%); and privately insured (62.1%). Patients mostly sought psilocybin to address only a psychiatric concern (75.9%); 27.6% anticipated naturalistic (non-state regulated) use. Most patients were deemed low risk for adverse events. Prevalence of prior challenging psychedelic experiences (CPE) was 17.2%; 58.6% reported lifetime psilocybin use. 86.2% endorsed >1 form of lifetime trauma. Of PPS completers (N=23, 79%), mean score was 91.3 (SD = 23.99). Scores did not significantly differ by insurance; consultation motivation; CPE; prior psilocybin or psychedelic use. Conclusion: Patients utilizing a novel consultation service demonstrate a high prevalence of trauma, prior psilocybin use, and baseline preparedness. While preliminary, this is among the first descriptions of patients seeking medical and psychiatric consultation when considering psilocybin and highlight the potential role of healthcare systems in providing evidence-based patient education and risk reduction as interest in psychedelics grows.

Objective: To evaluate long-term neurological, mental, and menstrual health outcomes using a mixed-methods approach among women approximately 2 years after concussion compared with non-head-injured controls. Setting: Participants were recruited from [University X] sites, including the Concussion Clinic, Emergency Departments, Student Health Clinic, and [University X] + Me registry (April 2023 to September 2025). Follow-up occurred October to November 2025. Participants: Eligible participants were assigned female at birth, aged 18 to 45 years, not using hormonal birth control, and, for the concussion group, diagnosed within 7 days of injury. Of 45 concussion patients and 29 controls recruited, 11 concussion patients (mean age 30.4 +/- 8.4 years) and 16 controls (31.3 +/- 7.4 years) completed follow-up. Main Measures: Post-concussion symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), depression using the Patient Health Questionnaire-9 (PHQ-9), and anxiety using the Generalized Anxiety Disorder-7 (GAD-7). Menstrual health was assessed using study-specific measures. Qualitative data captured perceived impacts on daily life, with recurring themes summarized using word clouds. Results: At follow-up, concussion patients reported significantly greater symptom burden (RPQ: 31.6 +/- 13.5 vs 9.4 +/- 9.8; p=0.0002; Hedges g=1.90), depression (PHQ-9: 9.5 +/- 6.5 vs 2.3 +/- 2.2; p=0.0005; g=1.60), and anxiety (GAD-7: 9.8 +/- 6.8 vs 2.8 +/- 3.0; p=0.0057; g=1.42). Qualitative findings highlighted persistent headaches, sleep difficulties, reduced interest, and effects on relationships and daily functioning. Conclusions: This study demonstrates significant long-term differences in symptom burden among women with concussions compared to controls. Findings highlight the importance of understanding real-world impacts to improve long-term care.

BackgroundSelf-compassion has shown to be an effective emotion regulation strategy, but its neural mechanisms remain understudied in adolescents with depression who suffer from social exclusion. This study employed event-related potentials to investigate the psychophysiological mechanisms underlying impaired self-compassion in adolescents with depression during social exclusion. MethodsThirty-seven adolescents with major depressive disorder (age = 16.46 {+/-} 2.02) and thirty-two demographically matched healthy controls (age = 16.54 {+/-} 2.29) completed a social exclusion scenario imagination task. This task presented participants with social exclusion scenarios, asking them to imagine themselves as the excluded individual and subsequently rate their negative emotions. The regulation session required participants to use self-compassionate statements to regulate their emotional responses while imagining and rate how much self-compassion they have engaged in; the non-regulation required them not to use those statements and rate their negative emotions immediately following imagination. EEG signals were recorded during the task, and the late positive potential (LPP) was analyzed to examine the neural responses associated with self-compassion regulation following social exclusion. ResultsCompared with the non-regulation condition, both groups showed less negative emotion during the self-compassion regulation condition. Adolescents with depression exhibited significantly lower self-compassion ratings than healthy controls, and showed a significantly smaller decrease in negative emotions. Higher self-compassion ratings were correlated with greater emotion regulation effect, particularly in adolescents with depression. Furthermore, LPP amplitudes were significantly higher in adolescents with depression than in healthy controls during both regulation and non-regulation conditions. ConclusionsAdolescents with depression were characterized by impairment in using self-compassion to downregulate negative emotions when confronted with social exclusion. LPP amplitudes were consistently elevated in adolescents with depression, underscoring their potential as a critical focus for psychophysiologically-informed therapies.

Background: Adolescent suicide is a leading cause of death in Australia, arising from multiple determinants. Psychological distress, lifestyle behaviours and socioeconomic factors are associated with adolescent suicidality. Existing research has predominantly employed cross-sectional designs, limiting our understanding of how these factors interact over time. Longitudinal and data-driven approaches are needed to help identify the factors associated with the emergence of suicidality throughout adolescence. Method: Participants aged 12-17 years completed longitudinal measures of suicidal ideation, psychological distress, sleep quality, mindfulness, physical activity, eating habits, and social connectedness. Subgroups were determined via hierarchical cluster analysis, based on average scores across later timepoints (9-15). ANOVA and pairwise effect size calculations were used to compare clusters across variables, and their preceding developmental trajectories were examined using generalised additive mixed models (across earlier timepoints; 1-8). Clusters were also compared on self-reported wellbeing, long-term suicidality, and socioeconomic status. Result: Three clusters characterised by low-, moderate-, and high-severity of suicidal ideation and psychological distress, and poorer sleep, social connectedness, physical activity, mindfulness, and eating habits were identified. Across earlier timepoints, the high-severity group showed consistently elevated suicidality and deteriorating wellbeing and lifestyle scores. Conclusion: Youth with high levels of suicidality had greater psychological distress, lower wellbeing, lower socioeconomic status, and poorer lifestyle behaviours. This subgroup was also found to have poorer scores on wellbeing and lifestyle factors in their early adolescence. Findings highlight the importance of early, preventative interventions targeting both mental health and lifestyle factors to reduce suicidality in adolescents.

Background Childhood adversity is linked to psychopathology risk and dysregulated stress reactivity; however, unified underlying neural mechanisms are unclear. A central visceral network, including the bed nucleus of the stria terminalis (BNST), amygdala and subgenual anterior cingulate cortex (sgACC), is implicated in affective processes and proximally controls stress reactivity. We examined relationships among childhood adversity, stressor-evoked neural activity/connectivity and affective and cardiovascular outcomes. Methods Participants were adults (n=97, mean age=27.32, SD=4.02, 57 females) uniformly distributed across physical abuse severity. Childhood adversity was assessed by threat (abuse or traumatic events) and socioeconomic deprivation (SED). Participants performed an fMRI stress task with cardiovascular recordings. Linear/curvilinear regressions were performed with threat and deprivation together as predictors of stressor-evoked activity/connectivity. Neural variables showing significant adversity associations were examined as predictors of affective symptoms/diagnoses or cardiovascular responses. Results Threat and SED displayed opposing curvilinear relationships with stressor-evoked amygdala and sgACC activity, respectively: at low and high adversity, amygdala reactivity was greater, whereas sgACC reactivity was blunted. Greater SED was associated with weaker BNST-sgACC connectivity. Blunted amygdala reactivity and lower sgACC reactivity were associated with greater post-traumatic stress symptoms. Affective diagnoses peaked at near-zero BNST-sgACC connectivity. Greater amygdala reactivity was associated with blunted diastolic blood pressure reactivity and recovery. Conclusions The curvilinear relationships suggest adversity-related vulnerability thresholds. Blunted amygdala, lower sgACC reactivity and weaker BNST-sgACC connectivity may confer affective risk, whereas heightened amygdala reactivity may confer cardiovascular risk. Our findings support a central visceral network pathway by which childhood adversity may contribute to affective and cardiovascular health.