This study explores among individuals with a major depressive episode (MDE) the potential impact of mixed features on the risk of suicide attempt, suicidal thoughts, self-harm intentions, and thoughts of death. Data from the French Mental Health in General Population (MHGP) survey (1999-2003) were analyzed, including 128 participants meeting criteria for MDE with mixed features (MDE with at least 3 manic symptoms) and 3,312 participants experiencing MDE without mixed features. Our primary analysis focused on suicide attempt, with additional examination of recent suicidal thoughts, self-harm intentions, and thoughts of death. Multivariable regression models were performed to adjust for potential confounding variables, including sociodemographics, previous suicide attempt, number of depressive symptoms, and psychiatric comorbidity. MDE with mixed features was significantly associated with an increased risk of suicide attempt (adjusted odds ratio [AOR] = 1.69; 95% CI, 1.26-2.25). This association did not significantly differ between men and women. Furthermore, the number of manic symptoms demonstrated a dose-dependent relationship with an increased risk of suicide attempt (AOR = 1.18; 95% CI, 1.07-1.30; < .001). Mixed features were also associated with suicide attempt among individuals with MDE and without recent suicidal thoughts (AOR = 2.74; 95% CI, 1.36-5.54). This study underscores the importance of assessing mixed features when evaluating the risk of suicide attempt in individuals with MDE. Mechanisms underlying this association might be independent of progression from thoughts of death to suicidal thoughts, suicidal intention, and ultimately, suicide attempt.

To evaluate the relationship between a predelivery history of concussion and risk of severe maternal mental illness. We conducted a population based cohort study of birthing people with a singleton livebirth accrued between 2007 and 2017 with follow-up to 2021 in Ontario, Canada. The primary outcome was severe maternal mental illness, defined as a psychiatric emergency department visit, psychiatric hospital admission, or self-harm or suicide in the 14 years after delivery. Cox proportional hazards regression generated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) comparing those with a history of a health care encounter for concussion between database inception and the index delivery date to those without a recorded health care encounter for concussion, adjusted for maternal age, parity, neighborhood income quintile, rural residence, immigration status, chronic conditions, history of interpersonal violence, and history of mental illness. Results were also stratified by history of mental illness. There were n = 18,064 birthing people with a history of concussion and n = 736,689 without a history of concussion. Those with a history of concussion had an increased risk of severe maternal mental illness compared to those without this history (14.7 vs 7.9 per 1,000 person-years; aHR 1.25, 95% CI, 1.20-1.31). After stratification by predelivery history of mental illness, the association was strongest in individuals with no mental illness history (aHR 1.33, 95% CI, 1.23-1.44). These findings indicate the need for early identification and screening of birthing people with a history of concussion, as well as ongoing long-term supports using trauma informed approaches to prevent adverse psychiatric outcomes.

When discussing neurotransmitters whose signaling plays an important role in psychiatric illnesses, serotonin and dopamine may be the first that come to mind. Although serotonin and dopamine have significant roles, the impact of norepinephrine signaling is often overlooked. A growing body of evidence suggests that hyperactivity of norepinephrine signaling is an underlying issue in psychiatric disorders; conversely, there is evidence to suggest that deficits in the noradrenergic system are just as significant. Hence, alterations in noradrenergic activity are better characterized as dysregulation rather than a reductive, outdated formulation of "too much" or "too little" activity. Therefore, symptoms such as agitation, irritability, hyperarousal, and insomnia could be treated by targeting the underlying pathophysiology related to noradrenergic dysregulation with targeted treatments. In a recent consensus panel meeting, 5 experts reviewed the available evidence of altered noradrenergic activity and its potential role in some of the most common psychiatric disorders. This Academic Highlights article summarizes their discussion and presents the panel's conclusions.

Cumulative data indicate that new protocols of hyperbaric oxygen therapy (HBOT) may induce neuroplasticity and improve clinical symptoms of patients suffering from posttraumatic stress disorder (PTSD). The aim of the current study was to evaluate the effects of HBOT on veterans with combat-associated PTSD (CA-PTSD) in a randomized, sham-controlled trial. Male veterans aged 25-60 years with CA-PTSD, with a Clinician-Administered PTSD Scale for (CAPS-5) score above 20, were included. Exclusion criteria included a history of traumatic brain injury, other psychiatric diseases, or contraindication to HBOT. Participants were randomly assigned to HBOT or sham intervention. Both interventions involved 60 daily sessions, with 90 minutes of either 100% oxygen at 2 atmospheres absolute (ATA) (HBOT) or 21% oxygen at 1.02 ATA (sham) with 5-minute air breaks every 20 minutes. CAPS-5 score, Beck Depression Inventory-II (BDI-II), the Depression, Anxiety and Stress Scale 21 Items (DASS-21), and resting-state functional magnetic resonance imaging (rsfMRI) were assessed at baseline and posttreatment, with the primary end point defined as a 30% reduction in CAPS-5 score from baseline. The study was conducted between February 2020 and July 2023. Of 63 veterans who underwent randomization, 56 completed the study protocol (28 in each group). The HBOT group showed a significant decrease in mean CAPS-5 total score, from 42.57 ±9.29 at baseline to 25.8±9.5 following HBOT (< .001) and 25.08± 13.08 at follow-up (< .001). The sham group demonstrated a significant increase in CAPS-5 total score from baseline to follow-up, from 45.11 ±8.99 to 47.75± 11.27 following HBOT (= .069) and 49.22± 10.26 at follow-up (= .011). Significant improvements in the depression domain of the DASS-21 questionnaire and BDI-II were demonstrated (=4.55, = .03 and =4.2, = .04, respectively). The stress and anxiety domains of DASS-21 did not reach statistically significant levels. Analysis of rsfMRI demonstrated improved connectivity within the 3 main networks (default-mode network, central-executive network, salience network) in HBOT vs sham groups. Dedicated HBOT protocol can improve PTSD symptoms of veterans with CA-PTSD. The clinical improvement was accompanied by enhanced functional connectivity demonstrated by rsMRI. ClinicalTrials.gov identifier: NCT04518007.

About 5%-10% of pregnancies in the US are exposed to cannabis with highest use reported during the first trimester. Two recent meta-analyses presented estimates of the risk of birth defects associated with prenatal exposure to cannabis; the larger and more recent meta-analysis pooled data from 18 cohort and 18 case-control studies with a total sample size of >19 million subjects. The meta-analyses found that prenatal exposure to cannabis was associated with a small but statistically significant increased risk of any birth defect (pooled odds ratios [ORs], 1.25-1.33); ORs were also significantly elevated for cardiovascular, gastrointestinal, nervous system, genitourinary, and musculoskeletal but not orofacial birth defects. The ORs were smaller and less likely to be statistically significant in adjusted analyses. These meta-analyses had strengths but also shortcomings. The strengths and shortcomings are explained in detail so that readers obtain a better understanding of how to critically assess findings in meta-analyses. One strength was the presentation of both unadjusted and adjusted pooled estimates; the former allow an understanding of risks in the average real world patient and the latter allow an understanding of the unique contribution of the exposure to the outcomes. Another strength was the presentation of cumulative meta-analyses which demonstrated from which calendar year onwards a finding became consistently statistically significant in the scientific literature. One shortcoming, in analyses of subcategories of birth defects, was the repeated representation of the same sample in the same forest plot; the many reasons why this is problematic are explained. Another shortcoming was the pooling of ORs obtained from cohort studies with those obtained from case control studies; conceptual and numerical reasons why this is problematic are also explained.

Little is known about differences between Black and White women with respect to the prevalence of postpartum mood disorders or symptom presentations. To determine the prevalence and characteristics of postpartum major mood disorders in Black and White women at 4-6 weeks after birth. This is a secondary analysis of a large-scale study designed to screen women for postpartum depression with the Edinburgh Postnatal Depression Scale (EPDS) and collect symptom data. Data were collected at an urban maternity hospital in an academic setting in Pittsburgh, Pennsylvania. Of the 2,019 women who screened positive and accepted a psychiatric diagnostic interview, 163 and 85 Black women had major depressive and bipolar disorders, respectively, and 508 and 177 White women had major depressive and bipolar disorders, respectively. Those with an EPDS score greater than or equal to 10 were offered a psychiatric assessment (in-person at home or by telephone) with the Structured Clinical Interview for using the Structured Interview Guide for the Hamilton Rating Scale for Depression, Atypical Depression Version symptom inventory, a questionnaire related to childhood and adulthood physical and sexual abuse, and the Short Form Survey 12. Participants who self-identified as Black or White were included in this analysis. Among screen-positive participants, no significant difference in the rate of major depressive disorder (40% Black and 35% White) was observed. However, bipolar disorder significantly differed between Black (19.2%) and White (11.5%) women. Additionally, symptom profiles differed between Black and White participants with major depressive disorder, and a high rate of traumatic experiences was reported by participants with major depression and bipolar disorder in both racial groups. An understanding of the different presentations of postpartum mood disorders between Black and White women, as well as trauma-informed care, can optimize postpartum health care through supporting advocacy efforts for resource allocation and health care delivery. Dataset from study at ClinicalTrials.gov identifier: NCT00282776.

Recent studies report a fluctuating course of attention-deficit/ hyperactivity disorder (ADHD) across development characterized by intermittent periods of remission and recurrence. In the Multimodal Treatment of ADHD (MTA) study, we investigated fluctuating ADHD including clinical expression over time, childhood predictors, and between- and within-person associations with factors hypothesized as relevant to remission and recurrence. Children with ADHD, combined type (N 483), participating in the MTA adult follow-up were assessed 9 times from baseline (mean age = 8.46) to 16-year follow-up (mean age = 25.12). The fluctuating subgroup (63.8% of sample) was compared to other MTA subgroups on variables of interest over time. The fluctuating subgroup experienced multiple fluctuations over 16 years (mean 3.58 SD = 1.36) with a 6- to 7-symptom within-person difference between peaks and troughs. Remission periods typically first occurred in adolescence and were associated with higher environmental demands (both between- and within-person), particularly at younger ages. Compared to other groups, the fluctuating subgroup demonstrated moderate clinical severity. In contrast, the stable persistent group (10.8%) was specifically associated with early and lasting risk for mood disorders, substance use problems in adolescence/ young adulthood, low medication utilization, and poorer response to childhood treatment. Protective factors were detected in the recovery group (9.1%; very low parental psychopathology) and the partial remission group (15.6%; higher rates of comorbid anxiety). In the absence of specific risk or protective factors, individuals with ADHD demonstrated meaningful within-individual fluctuations across development. Clinicians should communicate this expectation and monitor fluctuations to trigger as-needed return to care. During remission periods, individuals with ADHD successfully manage increased demands and responsibilities. ClinicalTrials.gov identifier: NCT00000388.

The suicide crisis syndrome (SCS), an acute negative affect state predictive of near-term suicidal behavior, is currently under review for inclusion as a suicide-specific diagnosis in the (). While the SCS has ample psychometric validation, it is critical to test its utility as a clinical tool within a real-world clinical setting. The present study investigates patterns of emergency department (ED) readmissions following implementation of an SCS-based risk assessment tool into the ED of a large, urban hospital system. Patterns of readmission rates to the ED in the 3 months following initial ED visit were evaluated for patients diagnosed with the SCS, after controlling for suicidal ideation (SI), self-harm behavior (SHB), and psychosis in the initial ED visit. All diagnoses were extracted from the electronic medical record. SCS diagnosis was based on the Abbreviated SCS Checklist (A-SCS-C), a clinician administered rating scale. Analysis of the SCS was performed on 213 patients consecutively admitted to the ED 9 months post-implementation of the A-SCS-C. Over one third (79; 37%) of patients were diagnosed with the SCS, over half 111 (52.1%) presented with SI and 8 (3.8%) with suicide attempt. After controlling for covariates, SCS diagnosis reduced readmission risk by approximately 72% (AOR = 0.281) for any reason and almost 75% (AOR = 0.257) for suicidal presentations, while SI and SHB upon initial ED visit either increased readmission risk or were noncontributory. The protective effect of the SCS was consistent across levels of severity of both SI and SHB. Use of the SCS appears to improve clinical outcome with suicidal patients presenting to the ED.

To provide an up-to-date estimate of subthreshold posttraumatic stress disorder (PTSD) in US military veterans based on a recently proposed working case definition of subthreshold PTSD and identify sociodemographic, psychiatric, and functional correlates of subthreshold PTSD relative to full PTSD. Data were analyzed from a nationally representative sample of US veterans. Probable lifetime subthreshold PTSD was operationalized as self reported endorsement of a potentially traumatic event (Criterion A); any 2 or 3 PTSD symptom clusters (Criteria B-E); symptom duration of more than 1 month (Criterion F); and PTSD symptom-related distress or functional impairment (Criterion G). The prevalence of lifetime full PTSD was 8.4% (95% CI, 7.2%-9.7%) and the prevalence of subthreshold PTSD was 3.9% (95% CI, 3.2%-4.8%). Subthreshold PTSD was associated with intermediately elevated odds of current and lifetime psychiatric disorders and clinical problems relative to veterans with no PTSD (adjusted odds ratios [OR] ranged from 1.7 for current alcohol use disorder and 3.3 for lifetime major depressive disorder [MDD]). Full PTSD was associated with even greater odds for most outcomes (OR ranges from 1.7 for current drug use disorder to 11.1 for lifetime MDD). Veterans with subthreshold PTSD reported intermediate-level reductions in mental, psychosocial, and cognitive functioning relative to veterans with no PTSD and full PTSD. Subthreshold PTSD is prevalent and associated with considerable psychiatric and functional distress/impairment among US veterans. Efforts to identify and treat veterans with subthreshold PTSD may lead to improvements in mental health and functioning in this population.

The first purpose of this study was to determine time to attainment of symptomatic remissions and recoveries of 2-12 years duration for those with borderline personality disorder (BPD) and patients with other personality disorders (OPDs); the second was to determine the stability of these outcomes. Two hundred ninety inpatients meeting both Revised Diagnostic Interview for Borderlines (DIB-R) and criteria for BPD and 72 patients with OPDs were assessed during their index admission using a series of semistructured interviews. The same instruments were readministered at 12 contiguous 2-year time periods. Patients with BPD were significantly slower to achieve remission or recovery (which involved good social and vocational functioning as well as symptomatic remission) than patients with OPD. However, those in both study groups ultimately achieved about the same high rates of remission (BPD patients: 77%-100%; patients with OPD: 97%-100%) but not recovery (37%-60% vs 68%-89%) by the time of the 24-year follow-up. In contrast, symptomatic recurrence (11%-40% vs 5%-10%) and loss of recovery (29%-59% vs 15%-42%) occurred more rapidly and at substantially higher rates among BPD patients than patients with OPD. Taken together, the results of this study suggest that sustained symptomatic remission is substantially more common than sustained recovery from BPD. They also suggest that loss of sustained recovery is more common than symptomatic recurrences for those with BPD.

To describe effects of gepirone extended-release (ER), an azapirone, on sexual function in patients receiving treatment for major depressive disorder (MDD). Sexual function was assessed in 1,767 patients (67% women) across five Phase 3 randomized controlled clinical trials comparing gepirone-ER against placebo or active treatment with selective serotonin reuptake inhibitors (SSRIs) for treatment of MDD. All five trials assessed sexual functioning in the short term (8 weeks), with three including long-term extensions of 16, 20, or 44 weeks. Sexual function was assessed prospectively and throughout trials via clinical interview and well-validated survey measures. Across studies, gepirone-ER was equivalent to placebo on sexual side effects and treatment-emergent sexual dysfunction. Relative to SSRIs, gepirone-ER was associated with significantly better effect on sexual function across time points studied. Evidence from patients without sexual dysfunction at baseline demonstrates superiority of gepirone-ER over SSRIs in the first few weeks of treatment, when patients are most vulnerable to the negative effects of sexual side effects on medication nonadherence/ discontinuation. Importantly, these benefits were maintained across treatment. Gepirone-ER was not associated with sexual dysfunction in patients with MDD. Rates of sexual side effects and treatment-emergent sexual dysfunction with gepirone-ER were comparable to those reported for placebo and lower than sexual side effects reported for active treatment with SSRIs.

This study assesses differences in opioid use disorder (OUD) treatment among sexually and gender diverse (SGD) vs non-SGD people. Using electronic health record data from a federally qualified health center, this retrospective cohort study explores OUD treatment for adults with an OUD diagnosis, as well as any clinic visit from January 2013 until June 2021 (N = 1,133), through review of medication prescriptions for OUD and OUD-related visits. Patients identifying as lesbian/gay had the lowest prevalence of OUD, with 1% (n = 231) of lesbian/gay patients having an OUD diagnosis, as compared to 1.5% (n = 560) of straight/heterosexual patients, 1.7% (n = 108) of bisexual patients, 1.4% (n = 44) of patients who identified as "something else," 1.6% (n = 26) of patients who "don't know" their sexual orientation, and 1.6% (n = 164) of patients who did not report their sexual orientation ( < .0001). There was not a statistically significant difference ( = .49) between OUD diagnosis in the transgender and gender diverse (TGD) cohort (1.5%, n = 117) and the cisgender cohort (1.4%, n = 1016). Straight/heterosexual patients were more likely than sexually diverse patients to be prescribed buprenorphine (44.3%, n = 248 vs 34.7%, n = 133, = .003), methadone (13.8%, n = 77 vs 9.4%, n = 36, = .04), and naloxone (47.0%, n = 263 vs 38.9%, n = 149, = .01). Cisgender patients were more likely to be prescribed buprenorphine than TGD patients (40.9%, n = 416 vs 31.6%, n = 37, = .05). TGD patients were more likely to be prescribed oral naltrexone than cisgender patients (19.7%, n = 23 vs 7.0%, n = 71, < .001). The straight/ heterosexual cohort had the lowest proportion of pharmacotherapy (19.3%, n = 108), individual psychotherapy (35.9%, n = 201), addiction and group therapy (12.9%, n = 72), case management (8.4%, n = 47), and complementary care visits (3.9%, n = 22). Straight/heterosexual patients had the highest proportion of outpatient medical visits (68.4%, n = 383). Transgender men had the highest proportion of individual therapy visits (80.8%, n = 21), compared to 53.7% (n = 29) of genderqueer/nonbinary patients, 51.4% (n = 19) of transgender women, 40.7% (n = 300) of cisgender men, and 40.6% (n = 113) of cisgender women ( < .001). The disparities in buprenorphine prescriptions and in outpatient medical visit access between the SGD and non-SGD cohorts highlight important priorities for culturally responsive interventions at clinical, organizational, and systems levels.

Suicide is a critical global health concern. Research indicates that generative artificial intelligence (GenAI) and large language models, such as generative pretrained transformer-3 (GPT-3) and GPT-4, can evaluate suicide risk comparably to experts, yet the criteria these models use are unclear. This study explores how variations in prompts, specifically regarding past suicide attempts, gender, and age, influence the risk assessments provided by ChatGPT-3 and ChatGPT-4. Using a controlled scenario based approach, 8 vignettes were created. Both ChatGPT-3.5 and ChatGPT 4 were used to predict the likelihood of serious suicide attempts, suicide attempts, and suicidal thoughts. A univariate 3-way analysis of variance was conducted to analyze the effects of the independent variables (previous suicide attempts, gender, and age) on the dependent variables (likelihood of serious suicide attempts, suicide attempts, and suicidal thoughts). Both ChatGPT-3.5 and ChatGPT-4 recognized the importance of previous suicide attempts in predicting severe suicide risks and suicidal thoughts. ChatGPT-4 also identified gender differences, associating men with a higher risk, while both models disregarded age as a risk factor. Interaction analysis revealed that ChatGPT-3.5 associated past attempts with a higher likelihood of suicidal thoughts in men, whereas ChatGPT-4 showed an increased risk for women. The study highlights ChatGPT-3.5 and ChatGPT-4's potential in suicide risk evaluation, emphasizing the importance of prior attempts and gender, while noting differences in their handling of interactive effects and the negligible role of age. These findings reflect the complexity of GenAI decision-making. While promising for suicide risk assessment, these models require careful application due to limitations and real-world complexities.

Cannabis is a psychoactive substance the availability and use of which, in various forms, has been liberalized in many countries across the world. Cannabis use, including by women of reproductive age, has become increasingly common, with (in some studies) >5% of women using the substance even during pregnancy to self treat nausea, vomiting, stress, anxiety, depression, insomnia, chronic pain, and other conditions. Women who use cannabis during pregnancy are more likely to have a medical or mental health condition; they are commonly unaware that cannabis is associated with pregnancy related risks. These risks arise from effects of cannabis on cannabinoid receptors in the placenta as well as from cannabis constituents that cross the placenta and act on receptors in the developing fetal brain; other mechanisms may also operate. This article examines recent cohort studies and meta-analyses on specific maternal and neonatal adverse outcomes associated with gestational exposure to cannabis. Maternal cannabis use during pregnancy is associated with small to moderately increased risks of gestational hypertension, gestational weight gain less than as well as greater than guidelines, and placental abruption. Maternal cannabis use during pregnancy is also associated with small to moderately increased risks of preterm birth (<36 weeks, <34 weeks, and <32 weeks), small for gestational age, low birth weight, neonatal intensive care unit admission, and fetal death. The risk of some of these adverse outcomes is greater with greater frequency of cannabis use. These adverse outcomes have been identified even in women who do not use other substances during pregnancy. Other adverse outcomes, such as major congenital malformations and neurodevelopmental disorders, are also reported (but are not discussed in this article). For these and other reasons, many professional bodies across the world are already discouraging women from using cannabis during pregnancy. It is important for pregnant women to be educated about cannabis and pregnancy related risks in a shared decision-making process.

In this meta-analysis, we evaluated changes in cognition for patients with schizophrenia spectrum disorders (SSD) with different durations of illness (DOIs). Records were identified through searches in PubMed, PsycINFO, CINAHL, and Cochrane until December 2021. We used terms related to SSDs, chronicity, course, and recovery. We included 57 longitudinal studies, with a follow-up length of at least 1 year, investigating changes in 10 domains of cognition of patients who are all diagnosed with SSD. Changes in cognition were analyzed through effect sizes of change between baseline and follow-up assessments within each study. These changes were evaluated in different subgroups of studies including patients with a DOI <5 years, 5-10 years, or >10 years. We also investigated the influence of 19 potential moderators on these changes in cognition. We found marginal improvements in overall cognition ( =0.13), small improvements in verbal memory ( = 0.21), processing speed ( = 0.32), marginal improvements in visual memory ( = 0.17), executive functioning ( = 0.19), and language skills ( = 0.13), and no significant improvements in the other cognitive domains. The largest improvements were achieved for patients with a DOI <10 years. Changes are more favorable for patients with a younger age, no schizophrenia diagnosis, female gender, higher education level, and low negative symptom severity. We observed only modest cognitive improvement in SSD almost exclusively in patients with early psychosis. Future research should focus on optimizing interventions targeting cognition in specific subgroups and the interrelationships with other life domains.