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Background: Although perinatal mental disorders are the most common health complication among women in the perinatal period, there is a huge gap in the implementation of related research findings in the health care system. We mapped the state of perinatal mental health (PMH) care in the WHO Europe region with aim to identify leading countries, which can serve as models for countries with less developed perinatal mental health care. Methods: Guidelines, policies, and documents related to screening and treatment services for PMH were searched as grey literature. Results were analysed to assess the status of PMH care in the WHO European countries and to identify gaps (absence of relevant service or documents). The state of perinatal mental health care was scored on a 0-5 scale. Results: The grey literature search resulted in a total of 361 websites. Seven countries (Belgium, Finland, Ireland, Netherlands, Sweden, UK, Malta) received full points for the presence of relevant PMH services or documents, while five countries received zero points. Most WHO European countries (48/53) have general mental health policies, but only 25 countries have policies specifically on perinatal mental health. Ten countries offer PMH screening, and 11 countries offer PMH service (of any type). Any PMH guidelines were provided in 23/53 countries. Conclusions: Perinatal mental health care is in its infancy in most WHO European countries. Leading countries (Belgium, Finland, Ireland, Netherlands, Sweden, UK, Malta) in PMH care can serve as conceptual models for those less developed and geopolitically close.
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OBJECTIVE: Review of recent literature dealing with the effect of antipsychotic use during pregnancy on early postpartum adaptation of exposed infants and the development of congenital malformations. RESULTS: The use of antipsychotics during pregnancy does not appear to lead to significantly higher risk of congenital malformations but may pose a greater risk for the early adaptation of the newborn (especially the risk of preterm birth and intensive care unit admission). The study to date face methodological limitations - lack of information on exact doses of antipsychotics, lack of control groups of women with psychiatric problems but not taking antipsychotics and failure to control for confounding factors. CONCLUSION: The available data suggest the relative safety of antipsychotics during pregnancy, provided that potential risks are known, and the woman and her baby are carefully monitored.
Subject(s)
Antipsychotic Agents , Fetal Development , Mental Disorders , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , Antipsychotic Agents/adverse effects , Mental Disorders/drug therapy , Pregnancy Complications/psychology , Fetal Development/drug effectsABSTRACT
OBJECTIVES: Pregnancy is often associated with reduced sleep quality and an increase in sleep disorders, such as restless leg syndrome, obstructive sleep apnea, and insomnia. There are few studies investigating the prevalence of parasomnias in pregnancy, although they may be expected to be a significant problem, as disturbed sleep in this time period in addition to these sleep disorders may trigger parasomnia episodes. METHODS: We conducted a survey using an online questionnaire focusing on a comparison of the prevalence of parasomnias in three time periods: 3 months before pregnancy, during pregnancy, and 3 months after delivery. We also inquired about psychiatric and neurological comorbidities, current anxiety and depression symptoms, and pregnancy complications. RESULTS: A total of 325 women (mean age 30.3 ± 5.3 years) participated in the online survey. The overall number of reported parasomnias increased during pregnancy compared to the 3 months before pregnancy (p < 0.001) and decreased after childbirth (p < 0.001). Specifically, we found a significant increase in sleepwalking (p = 0.02) and night terrors (p < 0.001), as well as in vivid dreams (p < 0.001) and nightmares (p < 0.001) during pregnancy. A similar significant increase during pregnancy was reported for head explosion (p < 0.011). In contrast, the number of episodes of sleep paralysis increased after delivery (p = 0.008). At the individual level, an increase in the severity/frequency of individual parasomnia episodes was also observed during pregnancy. Participants whose vivid dreams/nightmares persisted after delivery had higher BDI-II and STAI-T scores. Our data also suggest a significant impact of migraines and other chronic pain, as well as complications during pregnancy, on the presence of parasomnia episodes in our cohort. CONCLUSIONS: We have shown that the prevalence of parasomnias increases during pregnancy and needs to be targeted, especially by non-pharmacological approaches. At the same time, it is necessary to inquire about psychiatric and neurological comorbidities and keep in mind that more sleep disorders may be experienced by mothers who have medical complications during pregnancy.
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The impact of the microbiome on brain function and behavior has recently become an important research topic. We searched for a link between the gut microbiome and impulsive and violent behavior. We focused on critical factors influencing the microbiome establishment that may affect human health later in life, i.e., delivery mode, early-life feeding, and early antibiotic exposure. We searched PubMed, Web of Science, and the Cochrane Library. We included original human studies examining adults and children with impulsive and/or violent behavior that assessed the gut microbiota composition of participants, delivery mode, infant feeding mode, or early antibiotic exposure. Bibliographic searches yielded 429 articles, and 21 met the eligibility criteria. Two studies reported data on patients with schizophrenia with violent behavior, while 19 studies reported data on patients with attention-deficit hyperactivity disorder (ADHD). The results showed several bacterial taxa associated with ADHD symptomatology and with violent behavior in patients with schizophrenia. No association was found between delivery mode and impulsive behavior, nor did any articles relate infant feeding mode to violent human behavior. Those studies investigating early antibiotic exposure yielded ambiguous results. The heterogeneity of the data and the different methodologies of the included studies limited the external validity of the results. We found few studies that addressed the possible microbiome involvement in the pathophysiology of impulsive and violent behavior in humans. Our review revealed a gap in knowledge regarding links between the gut microbiome and these extreme behavioral patterns.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Gastrointestinal Microbiome , Infant , Child , Adult , Humans , Impulsive Behavior , Aggression , Anti-Bacterial AgentsABSTRACT
OBJECTIVE: To understand both, women´s perception of emotional difficulties in perinatal period and their related coping strategies. Further, we mapped and analysed help-seeking patterns utilized by these women to overcome their emotional difficulties. This study serve as an important piece of information for women-centred innovations in perinatal mental health care in Czechia, and more broadly in the region of Central and Eastern Europe. DESIGN: A qualitative study with an exploratory and descriptive approach using thematic analysis. SETTING: Online survey consisting of open-ended questions mapping women´s perception of emotional difficulties in perinatal period and their related coping strategies and help-seeking patterns. PARTICIPANTS: Two hundred women self-reporting emotional difficulties in perinatal period, from whom 108 (54 %) stated that they had sought professional help with their emotional difficulties. FINDINGS: Two themes were identified in the analysis of women´s perception of emotional difficulties including Experience of symptoms of mental disorders, and Mother-child relationship. Three themes were identified in the analysis of women´s coping with these difficulties (Personal resources, External resources, and No coping strategy used). Four themes were identified in the analysis of help seeking patterns utilized by study participants (Mental health specialists, Physicians of the first line of contact, Midwifes, and Peer consultants). KEY CONCLUSIONS: Emotional difficulties of perinatal women stemmed in both, general symptoms of mental disorders and specific concerns connected to mother-child relationship. Therefore, the perinatal mental health services should cover both topics, preferably by a multidisciplinary team. Women search information about perinatal mental health, so thus, easy to reach valid resources are needed. Finally, Czech perinatal women experiencing emotional difficulties utilize various help-seeking patterns. Some of them naturalistically utilize integrated stepped care even when it is not systematically established.
Subject(s)
Mental Disorders , Mental Health Services , Pregnancy , Female , Humans , Mental Health , Mental Disorders/psychology , Adaptation, Psychological , Qualitative ResearchABSTRACT
Objective: Postpartum depression (PPD) is a serious condition with debilitating consequences for the mother, offspring, and the whole family. The scope of negative outcomes of PPD highlights the need to specify effective diagnostics and treatment which might differ from major depressive disorder (MDD). In order to improve our clinical care, we need to better understand the underlying neuropathological mechanisms of PPD. Therefore, we conducted a systematic review of published neuroimaging studies assessing functional, structural, and metabolic correlates of PPD. Methods: Relevant papers were identified using a search code for English-written studies in the PubMed, Scopus, and Web of Science databases published by March 2022. Included were studies with structural magnetic resonance imaging, functional magnetic resonance imaging, both resting-state and task-related, magnetic resonance spectroscopy, or positron emission tomography. The findings were analyzed to assess signatures in PPD-diagnosed women compared to healthy controls. The review protocol was registered in PROSPERO (CRD42022313794). Results: The total of 3,368 references were initially identified. After the removal of duplicates and non-applicable papers, the search yielded 74 full-text studies assessed for eligibility. Of them, 26 met the inclusion criteria and their findings were analyzed and synthesized. The results showed consistent functional, structural, and metabolic changes in the default mode network and the salient network in women with PPD. During emotion-related tasks, PPD was associated with changes in the corticolimbic system activity, especially the amygdala. Discussion: This review offers a comprehensive summary of neuroimaging signatures in PPD-diagnosed women. It indicates the brain regions and networks which show functional, structural, and metabolic changes. Our findings offer better understanding of the nature of PPD, which clearly copies some features of MDD, while differs in others.
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BACKGROUND: Various risk factors to perinatal mental health disorders have been described; however, there is a dearth of data on the perspectives of women themselves regarding what increases the risk of psychological distress. This qualitative study explores women's perceptions of factors that increase the risk of perinatal psychological distress. AIM: The aim of this study was to elucidate women's perceptions of factors that increase the risk of perinatal psychological distress. METHODS: A qualitative design with an exploratory and descriptive approach is used. Women (N = 188) aged 18 to 45 years who self-report experiencing perinatal psychological distress complete an online survey. RESULTS: Perceived causes of perinatal psychological distress include: adverse experiences with childbirth and/or breastfeeding, negative attitudes of people close to the participant, financial and social challenges, health challenges, staff behavior in a maternity hospital, a challenging baby, family circumstances, and the new role as mother. CONCLUSION: Women's perceived causes of perinatal psychological distress may allow for women-centered innovations in perinatal mental health care. The results highlight the need to train maternity staff regarding perinatal mental health and communication. These findings can serve as important guidelines on women-centered planning of innovations of perinatal mental health care. Interventions need to focus on the role of partners and others close to women so as to support the women during the perinatal period.
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OBJECTIVE: To assess the accuracy of the Edinburgh Postnatal Depression Scale (EPDS) in screening for severe depression and other mental disorders in women at the end of puerperium. MATERIALS AND METHODS: We administered the Czech version of the EPDS to assess depressive symptoms and the Mini International Neuropsychiatric Interview to determine psychiatric dia-gnoses in 243 women at the end of their puerperium. Then, we determined the frequencies of severe depressive disorder and other psychiatric disorders in our cohort. Furthermore, we assessed the sensitivity, specificity, positive predictive value, negative predictive value, and other dia-gnostic variables for the presence of severe depression and other psychiatric disorders for different threshold scores on EPDS. We evaluated the detection potential of EPDS for detecting monitored mental disorders by using the receiver operating characteristic curve analysis and determining the area under the curve. RESULTS: Severe depressive disorder was present in 2.5% (95% CI: 1.1-5.3%) of women. Any monitored mental disorder was present in 13.6% (95% CI: 9.8-18.5%). The best sensitivity/specificity ratio for detecting major depressive disorder was found for the EPDS threshold score 11; sensitivity was 83% (95% CI: 35-99%) and specificity was 79% (95% CI: 74-84%). The EPDS 11 then achieved a sensitivity of 76% (95% CI: 58-89%) and specificity of 82% (95% CI: 76-87%) for the detection of any mental disorder of interest. CONCLUSION: Our results showed that the Czech version of EPDS has good internal consistency, and the EPDS score 11 achieves the best combination of sensitivity and specificity values for detecting major depressive disorder. Screening with EPDS in women at the end of puerperium can detect psychiatric disorders other than severe major depression.
Subject(s)
Depression, Postpartum , Depressive Disorder, Major , Depression, Postpartum/diagnosis , Depression, Postpartum/psychology , Depressive Disorder, Major/diagnosis , Female , Humans , Mass Screening/methods , Postpartum Period , Psychiatric Status Rating Scales , Reproducibility of ResultsABSTRACT
BACKGROUND: Neurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP. METHOD: We analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses. RESULTS: In primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations. CONCLUSIONS: This study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our ï¬ndings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.
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This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.
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Reports of subjective sleep impairments have been replicated in adults with bipolar disorder (BD), young BD patients, and even children of parents with BD. Furthermore, circadian rhythm alterations are a core feature of BD. Despite the impairment in circadian rhythms and altered sleep included in various heuristic developmental models of BD, thus far, biomarkers have not been sufficiently objectively validated. Thus, here, we assessed the rest-activity circadian rhythmicity and sleep macrostructure using actigraphy in a sample of unaffected child and adolescent offspring of bipolar parents (BO; n = 43; 21 females; 11.0 ± 3.2 years) and controls (n = 42; 17 females; 11.1 ± 3.4 years) comparable in sex (p = .4) and age (p = .7). All participants wore a MotionWatch 8 (Camntech, Cambridge, UK) actigraph on their nondominant wrist for ≥ 14 days and completed sleep diaries. Psychopathology was assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia and by subjective scales. The main areas of interest were rest-activity circadian rhythmicity, chronotype and sleep macrostructure. Subgroup analyses (child and adolescent subgroups) were conducted to identify physiological differences in sleep between these age groups. The BO and controls did not differ in the presence of current mood (p = .5) and anxiety (p = .6) disorders. The BO had shorter sleep time on free days (p = .007; effect size, Cohen´s d = 0.56), lower sleep efficiency on free days (p = .01; d = 0.47), lower prolongation of time in bed on free days (p = .046; d = 0.41), and lower social jet lag (p = .04; d = 0.5) than the controls. A longer sleep time on school days (p < .001; d = 0.21), lower prolongation of sleep time between school and free days (p = .008; d = 0.74), and larger difference in sleep onset latency between school days and free days (p = .009; d = 0.52) were observed in the adolescent BO than in the controls. The child BO had poorer sleep quality on free days than the controls (p = .02; d = 0.96). In all cases, the results remained significant after controlling for subthreshold mood and anxiety symptoms. The BO had less variable rest-activity rhythm than controls (p = .04; d = 0.32). No other significant differences between the BO and controls were observed in the rest-activity circadian rhythmicity and chronotype. The results showed decreased physiological catch-up sleep on free days in the BO, which may indicate a decreased need for sleep in this population. Thus, the decreased need for sleep observed in the unaffected BO may represent an endophenotype of BD.
Subject(s)
Bipolar Disorder/diagnosis , Chronobiology Disorders/diagnosis , Circadian Rhythm , Sleep Disorders, Circadian Rhythm/diagnosis , Sleep , Actigraphy , Adolescent , Affect , Anxiety/complications , Biomarkers/metabolism , Bipolar Disorder/complications , Child , Chronobiology Disorders/complications , Female , Fitness Trackers , Humans , Male , Parents , Phenotype , Schools , Sex Factors , Sleep Disorders, Circadian Rhythm/complications , Surveys and QuestionnairesABSTRACT
Background: Although a positive family history is the strongest predictor for bipolar disorder (BD), most offspring of BD parents (BO) will not develop the disorder. Identification of vulnerability markers for BD is essential for specific individual risk estimation. Impairments in cognitive functioning and the presence of specific temperament traits are considered promising candidates. Methods: Sixty-three BO (48% female; 11.8 ± 3.3 years) and 54 control offspring (CO; 44% female; 12.3 ± 3.2 years) comparable in sex (p = 0.4) and age (p = 0.4) were enrolled. Detection of current sub/threshold mood symptoms by the Kiddie Schedule for Affective Disorders and Schizophrenia and General Behavior Inventory was applied to separate BO into ultrahigh-risk (UHR) and high-risk (HR) subgroups. Cognitive functions were tested by the Developmental Neuropsychological Assessment II test battery, d2 Test of Attention, and Amsterdam Neuropsychological Tasks. Temperament was assessed by the Temperament in Middle Childhood and Early Adolescent Temperament Questionnaires. Results: The BO sample consisted of 5 BD, 17 UHR, and 41 HR participants. We did not observe any significant differences between the BO and CO groups or between the UHR, HR, and CO subgroups (Hedges' g = 0.21-0.39) in cognitive functioning. The BO differed significantly in some temperament traits from the CO (g = 0.42-0.61), while the UHR subgroup exhibited lower effortful control and attention focusing than both HR and CO participants (g = 0.92-1.19). Limitations: The cross-sectional design and wide age range of the sample limited our findings. Conclusions: Neuropsychological impairment does not seem to be a trait marker of BD in the premorbid stage. Temperament with low effortful control and low attention focusing might be associated with the development of mood disorders in BO.
Subject(s)
Adolescent Psychiatry , Child Psychiatry , Congresses as Topic , Adolescent , Career Mobility , Child , Humans , Mentoring , Societies, MedicalABSTRACT
OBJECTIVE: To determine current and lifetime psychopathology and assess quality of life (QoL) in offspring of a parent with bipolar disorder (BD). METHODS: We investigated 43 offspring of bipolar parents (high-risk offspring [HRO]) (mean age 12.5 ± 3.1; range 6.7-17.9 years) and 43 comparison offspring matched for sex, age, and IQ of healthy parents. Lifetime and current presence of Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) diagnoses were assessed using Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). We administered parent and self-report versions of General Behavior Inventory and the Screen for Child Anxiety-Related Emotional Disorders (SCARED). QoL was evaluated using the self-report questionnaire KIDSCREN-52. RESULTS: Thirty-seven HRO (86%) and 18 controls (42%) met DSM-5 criteria for at least one lifetime psychiatric diagnosis (adjusted OR = 7.20; 95% CI 2.27-22.81). Compared to controls, HRO had higher lifetime frequency of any mood disorder (33% vs. 2%, p < 0.001), anxiety disorder (60% vs. 14%, p < 0.001), and attention-deficit/hyperactivity disorder (26% vs. 5%, p = 0.01). After adjustment for confounders, only mood (OR = 13.05; 95% CI 1.41-120.60) and anxiety (OR = 9.69; 95% CI 2.75-34.31) disorders remained significantly more frequent in the HRO group. In comparison with controls, HRO scored lower in the following domains: QoL, social support and relationship with peers (p = 0.003; Cohen's d = 0.91), parent relationships and home life (p = 0.008; d = 0.67), as well as self-perception (p = 0.04; d = 0.55). CONCLUSIONS: In agreement with other studies, we found a higher rate of lifetime anxiety and mood disorders in children and adolescents at confirmed familial risk for BD. Reduction in QoL was already evident across a number of domains. Adult psychiatrists should incorporate into their assessment procedures targeted questions on the presence of psychopathology in offspring of their adult patients with severe mental disorders and child services should bridge with adult services providing accessible services to children of affected parents.
Subject(s)
Anxiety Disorders/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Bipolar Disorder , Child of Impaired Parents/psychology , Child of Impaired Parents/statistics & numerical data , Mood Disorders/epidemiology , Quality of Life , Adolescent , Case-Control Studies , Child , Czech Republic/epidemiology , Female , Humans , Male , Psychiatric Status Rating Scales , Risk FactorsABSTRACT
BACKGROUND: Impairment of sleep and circadian rhythm is a typical feature of bipolar disorder (BD). We carried out an exploratory cross-sectional case-control study to extend the knowledge of sleep characteristics in offspring at risk for BD. METHODS: We investigated 42 offspring of bipolar parents (OB) (mean age 12.5 ± 3.2) and 42 sex and age matched comparison offspring of healthy parents. We administered the Pediatric Sleep Questionnaire, the Morningness/Eveningness Questionnaire and The General Behavior Inventory Sleep Subscale (GBISS) to assess circadian preference, and to identify sleep impairment symptoms. In addition, the participants completed 14 days of actigraphy to characterise sleep and wake patterns. The current psychopathology profile was assessed using Kiddie Schedule for Affective Disorders and Schizophrenia. RESULTS: Prevalence of sleep disturbance symptoms was higher among OB than controls (headache after waking up, 17.9% vs. 2.4%, p = 0.03; excessive daytime sleepiness, 38.5% vs. 10.0%, p = 0.004; apparent tiredness at wake-up times, 43.6% vs. 15.0%, p = 0.007 and nightmares, 21.6% vs. 2.4%, p = 0.01), but the differences between groups were not significant after adjusting for current psychopathology. OB had higher GBISS total score (parental version, p < 0.001; self-assessment, p = 0.07) than the controls. OB had higher preference for eveningness than the controls (p = 0.047). According to the actigraphy, OB had longer sleep onset latency (p = 0.048) than the controls. CONCLUSION: Evidence suggests that the offspring of bipolar parents experience sleep disturbance symptoms, which was associated with psychopathology in this study. Prospective longitudinal sleep studies would clarify whether sleep disturbance could be a predictor of mood disorder onset in this high-risk population.
Subject(s)
Bipolar Disorder/physiopathology , Child of Impaired Parents/psychology , Parents/psychology , Sleep Wake Disorders/physiopathology , Actigraphy , Adolescent , Adult , Bipolar Disorder/psychology , Case-Control Studies , Child , Circadian Rhythm , Cross-Sectional Studies , Female , Humans , Male , Prospective Studies , Self-Assessment , Sleep Wake Disorders/diagnosis , Surveys and QuestionnairesABSTRACT
BACKGROUND: Approximately 30%-60% of adults diagnosed with bipolar disorder (BD) report onset between the ages 15 and 19 years; however, a correct diagnosis is often delayed by several years. Therefore, investigations of the early features of BD are important for adequately understanding the prodromal stages of the illness. METHODS: A complete review of the medical records of 46 children and adolescents who were hospitalized for BD at two psychiatric teaching centers in Prague, Czech Republic was performed. Frequency of BD in all inpatients, age of symptom onset, phenomenology of mood episodes, lifetime psychiatric comorbidity, differences between very-early-onset (<13 years of age) and early-onset patients (13-18 years), and differences between the offspring of parents with and without BD were analyzed. RESULTS: The sample represents 0.83% of the total number of inpatients (n=5,483) admitted during the study period at both centers. BD often started with depression (56%), followed by hypomania (24%) and mixed episodes (20%). The average age during the first mood episode was 14.9 years (14.6 years for depression and 15.6 years for hypomania). Seven children (15%) experienced their first mood episode before age 13 years (very early onset). Traumatic events, first-degree relatives with mood disorders, and attention deficit hyperactivity disorder were significantly more frequent in the very-early-onset group vs the early-onset group (13-18 years) (P≤0.05). The offspring of bipolar parents were significantly younger at the onset of the first mood episode (13.2 vs 15.4 years; P=0.02) and when experiencing the first mania compared to the offspring of non-BD parents (14.3 vs 15.9 years; P=0.03). Anxiety disorders, substance abuse, specific learning disabilities, and attention deficit hyperactivity disorder were the most frequent lifetime comorbid conditions. CONCLUSION: Clinicians must be aware of the potential for childhood BD onset in patients who suffer from recurrent depression, who have first-degree relatives with BD, and who have experienced severe psychosocial stressors.