Ventral prefrontal serotonin 1A receptor binding: a neural marker of vulnerability for mood disorder and suicidal behavior?

Mood disorders and suicidal behavior have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT1A) brain binding. However, it is unclear whether this reflects genetic effects or epigenetic effects of childhood adversity, compensatory mechanisms, or illness stress-related changes. We sought to separate such effects on 5-HT1A binding by examining high familial risk individuals (HR) who have passed through the age of greatest risk for psychopathology onset with and without developing mood disorder or suicidal behavior. PET imaging quantified 5-HT1A binding potential BPND using [11C]CUMI-101 in healthy volunteers (HV, N = 23) and three groups with one or more relatives manifesting early-onset mood disorder and suicide attempt: 1. unaffected HR (N = 23); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N = 26); and 3. HR-MOOD with previous suicide attempt (HR-MOOD + SA, N = 20). Findings were tested in an independent cohort not selected for family history (HV, MOOD, and MOOD + SA, total N = 185). We tested for regional BPND differences and whether brain-wide patterns distinguished between groups. Low ventral prefrontal 5-HT1A BPND was associated with lifetime mood disorder diagnosis and suicide attempt, but only in subjects with a family history of mood disorder and suicide attempt. Brain-wide 5-HT1A BPND patterns including low ventral prefrontal and mesiotemporal cortical binding distinguished HR-MOOD + SA from HV. A biological endophenotype associated with resilience was not observed. Low ventral prefrontal 5-HT1A BPND may reflect familial mood disorder and suicide-related pathology. Further studies are needed to determine if higher ventral prefrontal 5-HT1A BPND confers resilience, reducing risk of suicidal behavior in the context of familial risk, and thereby offer a potential prevention target.

Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior.

BACKGROUND: The serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to familial risk and resilience for suicidal behavior. METHODS: [11C]CUMI-101 positron emission tomography imaging to quantify regional brain 5-HT1A receptor binding was conducted in individuals considered to be at high risk for mood disorder or suicidal behavior on the basis of having a first- or second-degree relative(s) with an early onset mood disorder and history of suicidal behavior. These high-risk individuals were subdivided into the following groups: high risk resilient having no mood disorder or suicidal behavior (n = 29); high risk with mood disorder and no suicidal behavior history (n = 31); and high risk with mood disorder and suicidal behavior (n = 25). Groups were compared with healthy volunteers without a family history of mood disorder or suicidal behavior (n = 34). Participants underwent the Trier Social Stress Task (TSST). All participants were free from psychotropic medications at the time of the TSST and PET scanning. RESULTS: We observed no group differences in 5-HT1A receptor binding considering all regions simultaneously, nor did we observe heterogeneity of the effect of group across regions. These results were similar across outcome measures (BPND for all participants and BPp in a subset of the sample) and definitions of regions of interest (ROIs; standard or serotonin system-specific ROIs). We also found no group differences on TSST outcomes. Within the high risk with mood disorder and suicidal behavior group, lower BPp binding (ß = -0.084, SE = 0.038, P = .048) and higher cortisol reactivity to stress (ß = 9.25, 95% CI [3.27,15.23], P = .004) were associated with higher lethality attempts. There were no significant relationships between 5-HT1A binding and cortisol outcomes. CONCLUSIONS: 5-HT1A receptor binding in ROIs was not linked to familial risk or resilience protecting against suicidal behavior or mood disorder although it may be related to lethality of suicide attempt. Future studies are needed to better understand the biological mechanisms implicated in familial risk for suicidal behavior and how hypothalamic-pituitary-adrenal axis function influences such risk.

Increased burden of cardiovascular risk among youth suicide attempters.

BACKGROUND: Suicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals. METHODS: Participants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18-30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15-30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking. RESULTS: Suicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31-0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53-2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67-6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38-85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55-2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25-15.00, p = 0.53). CONCLUSIONS: Youth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.

Prospective evaluation of the DSM-5 persistent complex bereavement disorder criteria in adults: dimensional and diagnostic approaches.

BACKGROUND: We examine the performance of the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) persistent complex bereavement-related disorder (PCBD) criteria in bereaved adults to identify prolonged grief cases determined prospectively. METHODS: Bereaved adults (n = 138) were assessed at 8, 21, 32, 67, and 90 months after the sudden death of a spouse or close relative. We used latent class growth analysis to identify the longitudinal trajectories of grief assessed using the Inventory for Complicated Grief. To validate the trajectory that corresponded to prolonged grief, we examined the baseline predictors of these trajectories and their relationship with functional impairment. RESULTS: We found three distinct trajectories of grief reactions. One of these trajectories (13.8%) showed high and sustained grief reactions that persisted for almost 7.5 years after the death. Participants with prolonged grief showed greater functional impairment [relative risk ratio (RRR) = 0.82, 95% confidence interval (CI): 0.70 to -0.97; p = 0.02] and higher self-reported depression (RRR = 1.21, 95% CI 1.09 to 1.96; p = 0.001) than participants whose grief reactions subsided over time. The original PCBD (requiring 6 criterion C symptoms) criteria correctly identified cases (57.9-94.7%) with perfect specificity (100%) but low to high sensitivity (5.6-81.3%); however, its sensitivity increased when revising criterion C to require ⩾3 (45.5-94.1%). The dimensional approach showed high sensitivity (0.50-1) and specificity (0.787-0.97). CONCLUSIONS: We recommend revisions to the PCBD criteria, which are overly restrictive and may exclude cases with clinically significant grief-related distress and impairment. In the meantime, clinicians need to monitor grief symptoms over time using available dimensional approaches to reduce the burden of grief.

The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

BACKGROUND: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. METHODS: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. RESULTS: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2 = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2 = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2 = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2 = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2 = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. CONCLUSIONS: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Debate: The toll of the COVID-19 pandemic on children's risk for suicidal thoughts and behaviors.

The consequences of the COVID-19 pandemic on risk for suicidal thoughts and behaviors (STBs) in children are still not fully known. However, COVID-19 and the mitigation strategies to limit its transmission have affected children and adolescents through increased parental morbidity and mortality, increased poverty and financial strain, social isolation, and lost connectedness to school, peers, and afterschool activities. These are all associated with increased risk for psychiatric disorders and STBs in children. Mental health professionals and pediatric primary care settings need to monitor psychiatric symptoms and risk for STBs in children and especially among those who were directly affected during the pandemic in order to reduce the burden of the pandemic on children and families.

Commentary: The course of depression after childhood parental death - a reflection on Berg et al. (2016).

Berg et al.'s study highlights the long-lasting impact of childhood parental death on depression in adulthood in the absence of early preventive and intervention efforts. Given the long-term effects of childhood parental death, it seems that the most propitious time to intervene is early on after the death. Several prevention and intervention approaches have been shown to reduce the incidence of depression and to ameliorate its course and thus could be potential approaches to intervene with parentally bereaved children. Future longitudinal studies focused on children and adolescents are also needed to examine the biological pathways that set the stage for increased vulnerability across the life span following childhood parental death and adversity in order to inform novel targets for interventions.

Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate.

An increased abundance of runs of homozygosity (ROH) has been associated with risk for various diseases, including schizophrenia. Here we investigate the characteristics of ROH in Palau, an Oceanic population, evaluating whether these characteristics are related to risk for psychotic disorders and the nature of this association. To accomplish these aims we evaluate a sample of 203 cases with schizophrenia and related psychotic disorders-representing almost complete ascertainment of affected individuals in the population-and contrast their ROH to that of 125 subjects chosen to function as controls. While Palauan diagnosed with psychotic disorders tend to have slightly more ROH regions than controls, the distinguishing features are that they have longer ROH regions, greater total length of ROH, and their ROH tends to co-occur more often at the same locus. The nature of the sample allows us to investigate whether rare, highly penetrant recessive variants generate such case-control differences in ROH. Neither rare, highly penetrant recessive variants nor individual common variants of large effect account for a substantial proportion of risk for psychosis in Palau. These results suggest a more nuanced model for risk is required to explain patterns of ROH for this population.

Risk for Suicide Attempts Assessed Using the Patient Health Questionnaire-9 Modified for Teens.

Importance: Suicide is a leading cause of death in US youths. Objective: To assess whether screening with supplemental items 10 to 13 on the Patient Health Questionnaire-9 modified for teens (PHQ-9M) improves prediction of youth suicide attempts beyond the information provided by the first 9 items alone (the PHQ-9). Design, Setting, and Participants: This retrospective cohort study used a retrospective cohort of adolescents aged 12 to 17 years who were screened for depression in outpatient facilities within a pediatric health care system between January 1, 2016, and December 31, 2022, with up to 1 year of follow-up to assess the occurrence of suicidal behavior. Follow-up was completed on December 31, 2023. Exposure: Screening with the PHQ-9M. Main Outcomes and Measures: This study developed and compared prediction using 3 Cox proportional hazards regression models (CR-9, CR-13, and CR-3) of subsequent suicide attempts, determined by the hospital's electronic health records up to 1 year following the last PHQ-9M screening. The CR-9 model used the PHQ-9 and the CR-13 model used all 13 items of PHQ-9M. The CR-3 model used the 3 most impactful variables selected from the 13 PHQ-9M items and PHQ-9 total score. All models were evaluated across 4 prediction horizons (30, 90, 180, and 365 days) following PHQ-9M screenings. Evaluation metrics were the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPRC). Results: Of 130 028 outpatients (65 520 [50.4%] male) with 272 402 PHQ-9M screenings, 549 (0.4%) had subsequent suicide attempts within 1 year following the PHQ-9M screening. The AUROC of the CR-9 model in the 365-day horizon was 0.77 (95% CI, 0.75-0.79); of the CR-13 model, 0.80 (95% CI, 0.78-0.82); and of the CR-3 model, 0.79 (95% CI, 0.76-0.81); the AUPRC of the CR-9 model was 0.02 (95% CI, 0.02-0.03); of the CR-13 model, 0.03 (95% CI, 0.02-0.03); and of the CR-3 model, 0.02 (95% CI, 0.02-0.03). The 3 most impactful items using adjusted hazard ratios were supplemental item 13 (lifetime suicide attempts; 3.06 [95% CI, 2.47-3.80]), supplemental item 10 (depressed mood severity in the past year; 2.99 [95% CI, 2.32-3.86]), and supplemental item 12 (serious suicidal ideation in the past month; 1.63 [95% CI, 1.25-2.12]). All of the models achieved higher AUROCs as prediction horizons shortened. Conclusions and Relevance: In this cohort study of adolescent PHQ-9M screenings, the supplemental items on PHQ-9M screening improved prediction of youth suicide attempts compared with screening using the PHQ-9 across all prediction horizons, suggesting that PHQ-9M screening should be considered during outpatient visits to improve prediction of suicide attempts.

Adolescent, Parent, and Provider Perceptions of a Predictive Algorithm to Identify Adolescent Suicide Risk in Primary Care.

OBJECTIVE: To understand adolescent, parent, and provider perceptions of a machine learning algorithm for detecting adolescent suicide risk prior to its implementation primary care. METHODS: We conducted semi-structured, qualitative interviews with adolescents (n = 9), parents (n = 12), and providers (n = 10; mixture of behavioral health and primary care providers) across two major health systems. Interviews were audio recorded and transcribed with analyses supported by use of NVivo. A codebook was developed combining codes derived inductively from interview transcripts and deductively from implementation science frameworks for content analysis. RESULTS: Reactions to the algorithm were mixed. While many participants expressed privacy concerns, they believed the algorithm could be clinically useful for identifying adolescents at risk for suicide and facilitating follow-up. Parents' past experiences with their adolescents' suicidal thoughts and behaviors contributed to their openness to the algorithm. Results also aligned with several key Consolidated Framework for Implementation Research domains. For example, providers mentioned barriers inherent to the primary care setting such as time and resource constraints likely to impact algorithm implementation. Participants also cited a climate of mistrust of science and health care as potential barriers. CONCLUSIONS: Findings shed light on factors that warrant consideration to promote successful implementation of suicide predictive algorithms in pediatric primary care. By attending to perspectives of potential end users prior to the development and testing of the algorithm, we can ensure that the risk prediction methods will be well-suited to the providers who would be interacting with them and the families who could benefit.

Editorial: Prevention's Power: Depression Incidence Halved 15 Years After Participation in the Family Bereavement Program.

Prevention can be powerful. In the current issue of this Journal, Sandler et al. report on the long-term effects of the Family Bereavement Program (FBP), an intervention designed to promote resilience among parentally bereaved youth, as assessed 15 years after receipt of the initial intervention.1 Youth who received the FBP had half the rate of depression compared to those who received the comparison condition (13.46% vs 28.05%). This effect is as large or larger than many of our evidence-based treatments for depression, and considerably more enduring.2 An additional, elegant feature of this paper is that it identifies some mechanisms by which the FBP appears to exert its preventive effects.

Fetal inflammatory response and risk for psychiatric disorders.

Inflammation contributes to numerous neuropsychiatric disorders, especially those that first appear in childhood. Maternal intrauterine environment, including the placenta, has a role in brain development and risk for neuropsychiatric disorders. This study examines the link between fetal inflammatory syndrome (FIRS), which is placental inflammation in the peri-partem period, and neuropsychiatric disorders during childhood.This is a retrospective cohort study using data from electronic medical records over a 19-year period at one women's hospital. The study includes 4851 children born with placentas meeting criteria for and 31,927 controls identified with normal placentas born during the same period. To be diagnosed with FIRS placenta must contain chorionic vasculitis and/or funisitis. Children had to be in study period for at least 5 years. The primary outcome of the study is incidence of neuropsychiatric disorders during childhood. The secondary outcomes were psychiatric medications prescribed, and psychiatric hospitalizations and treatment. Children born to placentas meeting criteria for FIRS were more likely to be diagnosed with neuropsychiatric disorders (OR = 1.21, CI 95% [1.09,1.35]). Specifically, they were more likely to be diagnosed with autism spectrum disorder (OR = 1.35, CI 95% [1.08, 1.67]), ADHD (OR = 1.27, CI 95% [1.07, 1.49]), conduct disorder (OR = 1.50, CI 95% [1.24, 1.81]), PTSD (OR = 2.46. CI 95% [1.21, 5.04]), adjusting for maternal history of psychiatric disorders, intra-partem substance use, and prescriptions of anti-inflammatory drugs. Children born with placental inflammation are at an increased risk to develop neuropsychiatric disorders. This has profound implications for future research, and early detection, monitoring, and treatment in these children.

Smaller cornu ammonis (CA3) as a potential risk factor for suicidal behavior in mood disorders.

Mood disorders and suicidal behavior have moderate heritability and familial transmission, and are associated with smaller hippocampal volumes. However, it is unclear whether hippocampal alterations reflect heritable risk or epigenetic effects of childhood adversity, compensatory mechanisms, illness-related changes, or treatment effects. We sought to separate the relationships of hippocampal substructure volumes to mood disorder, suicidal behavior, and risk and resilience to both by examining high familial risk individuals (HR) who have passed the age of greatest risk for psychopathology onset. Structural brain imaging and hippocampal substructure segmentation quantified Cornu Ammonis (CA1-4), dentate gyrus, and subiculum gray matter volumes in healthy volunteers (HV, N = 25) and three groups with one or more relatives reporting early-onset mood disorder and suicide attempt: 1. Unaffected HR (N = 20); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N = 25); and 3. HR with lifetime mood disorder and a previous suicide attempt (HR-MOOD + SA, N = 18). Findings were tested in an independent cohort not selected for family history (HV, N = 47; MOOD, N = 44; and MOOD + SA, N = 21). Lower CA3 volume was found in HR (vs. HV), consistent with the direction of previously published findings in MOOD+SA (vs. HV and MOOD), suggesting the finding reflects a familial biological risk marker, not illness or treatment-related sequelae, of suicidal behavior and mood disorder. Familial suicide risk may be mediated in part by smaller CA3 volume. The structure may serve as a risk indicator and therapeutic target for suicide prevention strategies in high-risk families.

Risk for Suicidal Behavior After Psychiatric Hospitalization Among Sexual and Gender Minority Patients.

Importance: The months following inpatient psychiatric hospitalization are a period of high risk for suicidal behavior. Sexual and gender minority (SGM) individuals have elevated risk for suicidal behavior, but no prior research has examined whether SGM inpatients have disproportionate risk for suicidal behavior following discharge from psychiatric hospitalization. Objectives: To evaluate whether SGM patients have elevated risk for suicidal behavior following discharge from psychiatric hospitalization compared with heterosexual and cisgender patients and to examine whether differences in risk across groups were accounted for by demographic characteristics and clinical factors known to be associated with suicidal behavior. Design, Setting, and Participants: This prospective cohort study was conducted from August 2017 to July 2021 among inpatients aged 18 to 30 years who were voluntarily enrolled during psychiatric hospitalization. The study was conducted at an inpatient psychiatric hospital, with prospective data collected via follow-up visits and electronic health records. Main Outcomes and Measures: Onset and/or recurrence of suicidal behavior following discharge from psychiatric hospitalization, assessed at follow-up visits and through electronic health records. Results: A total of 160 patients were included, with 56 sexual minority (SM) and 15 gender minority (GM) patients. The median (IQR) age of the patients was 23.5 (20.4-27.6) years, 77 (48%) reported male sex assigned at birth, and 114 (71%) identified their race as White. During the follow-up period, 33 suicidal behavior events occurred (among 21% of patients). SM (hazard ratio [HR], 2.02; 95% CI, CI, 1.02-4.00; log-rank P = .04) and GM (HR, 4.27; 95% CI, 1.75-10.40; log-rank P < .001) patients had significantly higher risk for suicidal behavior compared with their heterosexual and cisgender counterparts, respectively, in bivariable analyses. Risk between SM and heterosexual patients was not different after controlling for demographic characteristics and clinical factors associated with suicidal behavior. GM patients exhibited elevated risk during the 100 days following discharge even after controlling for demographic and clinical characteristics (HR, 3.80; 95% CI, 1.18-11.19; P = .03). Conclusions and Relevance: Within this cohort study of psychiatric patients, SGM patients had higher risk for suicidal behavior than non-SGM patients following discharge. While SM patients' risk was accounted for by clinical characteristics, GM patients' risk for suicidal behavior was not accounted for by their acute psychiatric state on admission. Future studies with larger subsamples of GM individuals are needed, and inpatient clinicians must attend to the unique needs of SGM individuals to ensure they receive affirming services.

Longitudinal effects of parental bereavement on adolescent developmental competence.

The aim of this study is to assess the impact of sudden parental bereavement on subsequent attainment of developmental competencies. This longitudinal study reports on 126 youth bereaved by sudden parental death (suicide, accident, or natural death) and 116 demographically similar nonbereaved controls assessed at 9, 21, 33, and 62 months after parental death, and at comparable times in controls. Half were female and 84.7% Caucasian. Youths and care-giving parents were assessed on psychiatric disorders, psychological characteristics, and contextual variables antecedent and subsequent to bereavement. At Month 62, at which time youth on average aged 18.4 years (SD = 3.1), participants were assessed on developmental competence using an adaptation of the Status Questionnaire, peer attachment using the Inventory of Parent and Peer Attachment, and educational aspirations using the Future Expectations Scale. The bereaved and nonbereaved groups were compared using univariate and multivariate statistics, including path analyses. On univariate analyses, bereaved youth had more difficulties at work, less well-elaborated plans for career development, lower peer attachment, and diminished educational aspirations. The effects of bereavement were most commonly mediated via its effects on offspring and caregiver functioning and family climate, even after adjusting for the impact of predeath characteristics. Outcomes were unrelated to age at the time of parental death, gender of the deceased parent, or cause of death. Children who lost a parent to sudden death evidenced lower competence in work, peer relations, career planning, and educational aspirations, primarily mediated by the impact of bereavement on child and parental functioning and on family climate.

Opioid use as a proximal risk factor for suicidal behavior in young adults.

INTRODUCTION: There is a concomitant rise in suicide rates with the prevalence of opioids involved in overdose deaths, especially among adolescents and young adults. However, there are limited studies on whether opioid use prospectively predicts suicidal behavior in youth. METHODS: Our sample included 183 psychiatric patients (18-30 years) admitted for a suicide attempt (SA), have current suicidal ideation (SI), and psychiatric controls without ideation or attempt (PC). Suicidal behavior was assessed using the Columbia Suicide Severity Rating Scale. We also recruited a healthy control group (HC; n = 40). Patients and controls were followed over a year. ANOVA, regression, and cox regression were used. RESULTS: Suicide attempt (ß = 0.87, CI [0.1-1.6], p = 0.02) and SI [(ß = 0.75, CI [0.03-1.5], p = 0.04) were significantly more likely than HCs to have used opioids in the past year at baseline. Opioid use was associated with increased anxiety symptoms (ß = 0.75, CI [0.001-1.5], p = 0.05), PTSD symptoms (ß = 3.90, CI [1.1-6.7], p = 0.01), and aggression (ß = 0.02, CI [0.01-0.04], p = 0.02). Opioid use in the month prior to hospitalization predicted SA at 6 months (OR = 1.87, CI [1.06-3.31], p = 0.032). CONCLUSIONS: Opioid use is a proximal predictor for SA. These findings may help clinicians better identify patients at risk for suicidal behavior, allowing for more personalized treatment approaches.

Cardiac vagal control in response to acute stress during pregnancy: Associations with life stress and emotional support.

Life stressors during pregnancy can disrupt maternal stress regulation and negatively impact offspring health. Despite the important role of cardiac vagal control (e.g., heart rate variability; HRV) in stress regulation, few studies have investigated how life stressors and emotional support influence vagal control during pregnancy. This study aimed to (a) characterize patterns of cardiac vagal control in response to a stressor administered in pregnancy, and (b) examine the effects of life stress and emotional support on vagal control during rest, reactivity, and recovery. Participants included 191 pregnant women (79% Black; 21% White) living in an urban U.S. city (73% receiving public assistance). Heart rate (HR) and HRV (indexed by RMSSD) were recorded continually during the preparation, task, and recovery periods of the Trier Social Stress Test (TSST). Participants reported recent life stressors (e.g., relationship problems, financial hardship) and emotional support. Piecewise growth curve modeling was used to model rates of reactivity and recovery, adjusting for gestational age at time of assessment and recent health problems. Life stress predicted greater HR and HRV reactivity to the TSST as well as greater HRV recovery (vagal rebound). However, associations were only evident for women reporting high emotional support. Results suggest that pregnant women living with frequent life stressors may exhibit more rapid autonomic responses to acute stress, including more rapid vagal rebound after stressors, potentially reflecting physiological adaptation to anticipated high-stress environments; emotional support may enhance these responses. Studies are needed to investigate long-term health outcomes related to this stress response pattern.

Early Cortisol and Inflammatory Responses to Parental Cancer and Their Impact on Functional Impairment in Youth.

PURPOSE: Chronic stress is associated with increased risk for maladaptive psychological responses during childhood, adolescence, and young adulthood. Adults exposed to chronic stress during childhood exhibit dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity and inflammation. There are no studies examining the impact of stress on biological stress responses and functional impairment in adolescents and young adults early after the onset of a stressor. METHODS: The sample consisted of 59 offspring, aged 11-25 years, 33 of parents diagnosed with cancer and 26 controls from families with no cancer or severe chronic illness in parents or siblings. Cancer patients and their families were recruited within an average of 62 days (SD = 35.9) and followed at 6 and 9 months later. Functional impairment was assessed and hair cortisol concentrations (HCC), salivary cortisol, and inflammatory markers were measured. Mixed regression analyses were conducted. RESULTS: The stress group showed higher functional impairment (ß = -5.5, 95% CI (-10.4, -0.06), p = 0.03, d= -0.40) and HCC (ß = 10.5, 95% CI (-5.5, -0.50), p < 0.001, d = 1.43). However, HCC were reduced over time in the stress group (ß= -0.3, 95% CI (-0.04, -0.01), p < 0.001, d = -1.08). Higher total cortisol output was associated with increased functional impairment over time (ß = -3.0, 95% CI (-5.5, -0.5), p = 0.02, d = -0.60). CONCLUSIONS: Parental cancer is associated with early increase in cortisol, which was associated with increased functional impairment in offspring. Clinicians need to assess and monitor psychiatric symptoms and functioning in these offspring early on following parental cancer diagnosis.

Signaling networks in inflammatory pathways and risk for suicidal behavior.

BACKGROUND: Suicide is a leading cause of death in the young adult population, with few biological markers identified thus far to be associated with suicidality. Cytokines (including IL-6 and TNFα) may contribute to increased risk for depression and suicidality. Few studies have examined the associations of cytokine mRNA expression with depression and suicidal ideation and behavior. This study examines these associations and whether cytokine signaling networks differentiate suicide attempters (SA), suicide ideators (SI), and healthy controls (HC). METHODS: Cytokine pathway marker (CPM; e.g. cytokines and proteins in cytokine signaling pathways) mRNA gene expression in whole blood was examined in suicide attempters (n = 38), suicide ideators (n = 38), and healthy controls (n = 36). Between-group differences in CPM gene expression were examined. We also examined association of the mRNA of these genes with the severity of depression and suicidal ideation. Novel Gaussian Graphical Model (GGM) techniques were utilized to examine between-network partial correlation differences in cytokine signaling networks relevant to IL-6 and TNFα signaling pathways. RESULTS: The severity of depression symptoms was positively associated with TNFα mRNA levels and negatively associated with IL-10 mRNA levels, but CPM expression was not associated with suicidal ideation severity. There were no between-group differences in CPM markers among healthy controls, SI and SA groups after correcting for multiple comparisons. In network analyses, we found suggestive results of between-group network differences between SI and control groups in gene pairs with IL-6R and STAT3 as common nodes. DISCUSSION: In a cohort of suicide attempters and ideators, TNFα and IL-10 mRNA levels appear to be associated with depressive symptomology, consistent with elevation of pro-inflammatory cytokine production and reduction of anti-inflammatory cytokine production. Additionally, cytokine signaling networks may differentiate suicide ideators from healthy controls based on between-network differences, with differences possibly related to relationships of IL6R or STAT3 with other components of cytokine signaling networks.

Corpus callosum volume in children with autism.

The corpus callosum (CC) is the main commissure connecting the cerebral hemispheres. Previous evidence suggests the involvement of the CC in the pathophysiology of autism. However, most studies examined the mid-sagittal area and investigations applying novel methods are warranted. The goal of this investigation is to apply a volumetric method to examine the size of the CC in autism and to identify any association with clinical features. An MRI-based morphometric study of the total CC volume and its seven subdivisions was conducted and involved 22 children with autism (age range 8.1-12.7 years) and 23 healthy, age-matched controls. Reductions in the total volume of the CC and several of its subdivisions were found in the autism sample. Associations were observed between CC structures and clinical features including social deficits, repetitive behaviors, and sensory abnormalities. Volumetric alterations of the CC observed in this investigation are consistent with midsagittal area tracings of decreased CC size in autism. These findings support the aberrant connectivity hypothesis with possible decrease in interhemispheric communications.