Onset Of Bipolar Disorder Research Articles

Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies

AbstractIntroductionEarly onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old).MethodsData from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm.ResultsThe safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P<0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P<0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin.FundingServier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.

The effect of pandemic as a trigger for first episode bipolar disorders

IntroductionThe traumatic effects of COVID-19 pandemic is well studied in community and fragile groups. The association between COVID-19 infection and development of severe mood disorders have not well studied.ObjectivesNonetheless the casual relation or stressor effects of Covid-19 pandemic on chronic psychiatric illness is not known yet. The present study is aimed to investigate the effects of pandemic as a triggering factor in first episode Bipolar disorder (BD) patients that onset after pandemic.MethodsThe study included a total sample of 55 patients diagnosed with first episode BD according to DSM-5 criteria.The two groups of patients that illness onset was before (BP)and after pandemic (AP), were investigated and compared for psychopathology and life evet stressors. Impact of Event Scale-Revised (IES-R) for PTSD symptoms, Generalize Anxiety Disorder scale for anxiety symptoms, The Montgomery–Åsberg Depression Rating Scale (MADRS) to examine depressive symptoms; and Young Mania rating Scale (YMRS) for manic symptoms, Brief Psychiatric Rating Scale-18 (BPRS) was used for psychotic symptoms.ResultsThe statistical analyses were performed using the Statistical Package for Social Science, version 26. Thirty-five patients that illness onset before pandemic and 20 patients that illness onset after pandemic were compared.The significant differences were come up in some clinical features between the two groups. The alcohol and substance abuse were higher in AP group. The severity of psychotic and manic symptoms were higher in AP group. The hospitalization was higher in AP group. The number of stressor events was higher and PTSD symptoms was more severe in the AP group also.ConclusionsThe effects of Covid-19 pandemic seems have a triggering role in onset of first episode BD. This effect whether cause biological or psychological stress in onset of illness is not known yet. The casual phenomenon of Covid-19 pandemic should be investigated for chronic psychiatric illness as BD in future studies.Disclosure of InterestNone Declared

Course of bipolar disorder in patients with Childhood maltreatment

IntroductionPatients with mood disorders have the greater frequency of childhood trauma compared with the general population, and adverse childhood experiences can exert a negative impact on their clinical course. Therefore, many studies confirmed the relationship between childhood traumas and the disadvantageous features of the illness course.ObjectivesThe aim of this study was to determine the impact of negative childhood experiences on the clinical course of bipolar disorder.MethodsIt was a cross-sectional descriptive and analytical study involving patients diagnosed with bipolar disorder and followed in the psychiatric department at the University Hospital of Sfax (Tunisia).Personal information form and Childhood trauma questionnaire (CTQ) were used for data acquisition. Euthymia was defined as a score on the Montgomery-Åsberg Depression Rating Scale (MADRS) not higher than 14 and by a score on the Young Mania Rating Scale (YMRS) not higher than seven.ResultsWe included 35 patients. Their mean age was 46.69 ± 12.01 years with a sex ratio (M/F)=0.45.The average onset of bipolar disorder was 28.37±10.26 years and the average disease duration was 18.26 ± 11.55 years.Almost the third of our population had a suicidal attempt (31.42%) and a violence history (28.57%). A family history of bipolar disorder was found in 57.14% of the patients.The patients have been hospitalized at least once in 42.85% of cases.Our patients have presented psychotic symptoms in 51.42% of cases and mixed characteristics in 57.14% of cases.Emotional, physical and sexual abuse were reported by 42.85%, 37.14% , 31,42% of patients, respectively, while 74,28% and 42.85% of patients reported physical neglect and emotional neglect.Early age at illness onset was significantly associated with total CTQ score (p=0.014) and the subtype sexual abuse (p=0.009). The presence of psychotic symptomswas significantly associated with total CTQ score (p=0.003) and emotional neglect (p=0.025). Physical neglect was associated with mixed characteristics (p=0.015). Emotional abuse was associated with a greater number of hospitalisations (p=0.023).ConclusionsOur results suggest that childhood trauma is associated with a more severe course of bipolar illness. Clinical assessment of patients with bipolar disorder should include investigation of exposure to childhood trauma in order to determine appropriate therapeutic strategies.Disclosure of InterestNone Declared

New-Onset Bipolar Disorder in Late Life: a case report and review of literature

IntroductionThe elderly represents the fastest growing group of the population. It is fair to assume that the portion of old age patients suffering from bipolar disorder will grow in a similar manner. Elderly patients represent approximately 25% of the bipolar population. Summarizing, 5–10% of patients were 50 years of age when they experienced their first manic episode, constituting the subgroup of late onset bipolar disorder (LOBD).ObjectivesThe purpose of this case report and literature review is to emphasise the importance of LOBD in old population and to highlight its still sparse-knowledge.MethodsDescriptive case study and review of literature (Arnold,I. et al. Old Age Bipolar Disorder—Epidemiology, Aetiology and Treatment. Medicina 2021,57,587; Baldessarini et al. Onset-age of bipolar disorders at six international sites. J Affect Disord 2010;121(1-2):143-6).ResultsA 60-year-old woman is brought to the emergency department for evaluation by her family. Over the past 7 days, the patient has become increasingly irritable and argumentative, is sleeping less, is talking faster than usual and has begun to express paranoid concerns about her students “stealing my exam”. The patient is a university professor.In the assessment interview she is hyperverbal, expansive, and grandiose. The family has also just recently discovered that she has spent a large sum of money on the Internet.She has no history of psychiatric contact or substance use disorders; however, she has a family history of severe depression.In the absence of any plausible non-psychiatric condition that could mimic or induce mania, the working diagnosis is bipolar I disorder, most recent episode (MRE) manic with psychotic features.Image:Image 2:ConclusionsThe share of older age bipolar disorder will grow constantly in the next decades and further research on this neglected patient group is urgently required.Disclosure of InterestNone Declared

Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study.

Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways. We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning. A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions. Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers.

Bipolar disorder and sexuality: a preliminary qualitative pilot study

BackgroundIndividuals with mental health disorders have a higher risk of sexual problems impacting intimate relations and quality of life. For individuals with bipolar disorder (BD) the mood shifts might to a particular degree affect their sexual function with possible hypersexual interest during manic episodes and low sexual interest during depressive episodes. The diagnosis is often given in late adolescence, which may impact sexual identity and development. Only a few studies have looked at BD and sexual life, with no qualitative research on the topic.We conducted a qualitative pilot study exploring sexuality in connection to mood swings in five participants with BD.ResultsThematic content analysis revealed five themes: (1) sexual drive and impulses, (2) sexual behavior, (3) thoughts and feelings in relation to sexual issues, (4) intimate relationships, and (5) sexuality and identity. During manic episodes the participants described having a higher sexual drive, leading for some to more sexual interactions. During depressed episodes, the sexual drive in the three female participants was low, however, in the two men, rather than a reduced sexual drive, a more self-destructive way of engaging in sex prevailed. The sexual outgoing behavior during manic phases was described as joyful, with no feelings of shame connected to it. However, the shifts in sexual drive connected to mood shifts affected the participants’ relationships negatively. Further, all the participants described having outgoing sexual behavior in their youth.ConclusionsOverall, changes in sexual drive may act as a trigger or early warning symptoms of new episodes, pinpointing the clinical relevance of addressing sexuality in individuals with BD. In general, sexual drive followed affective episodes. However, during depressive episodes sex could be, instead of reduced drive, associated with negative feelings.All participants described having an outgoing sexual behavior in their youth before the onset of BD, which might be essential to consider if there is a clinical suspension of BD in an individual.

Postpartum-onset obsessive-compulsive disorder: A harbinger of bipolar disorder.

Postpartum-onset obsessive-compulsive disorder: A harbinger of bipolar disorder.

Outcome Prediction for Patients with Bipolar Disorder Using Prodromal and Onset Data

Background: Predicting the outcomes of serious mental illnesses including bipolar disorder (BD) is clinically beneficial, yet difficult. Objectives: This study aimed to predict hospitalization and mortality for patients with incident BD using a deep neural network approach. Methods: We randomly sampled 20,000 US Veterans with BD. Data on patients’ prior hospitalizations, diagnoses, procedures, medications, note types, vital signs, lab results, and BD symptoms that occurred within 1 year before and at the onset of the incident BD were extracted as features. We then created novel temporal images of patient clinical features both during the prodromal period and at the time of the disease onset. Using each temporal image as a feature, we trained and tested deep neural network learning models to predict the 1-year combined outcome of hospitalization and mortality. Results: The models achieved accuracies of 0.766–0.949 and AUCs of 0.745–0.806 for the combined outcomes. The AUC for predicting mortality was 0.814, while its highest and lowest values for predicting different types of hospitalization were 90.4% and 70.1%, suggesting that some outcomes were more difficult to predict than others. Conclusion: Deep learning using temporal graphics of clinical history is a new and promising analytical approach for mental health outcome prediction.

Depression and suicidal ideation among Pakistani rural areas women during flood disaster

Whether a history of premenstrual dysphoric disorder (PMDD) is associated with a subsequent risk of major affective disorders remains unclear. This study aimed to examine the risk of unipolar depression and bipolar disorder in women with PMDD compared with those without PMDD. This study used data from the Taiwan National Health Insurance Research Database. Women who were diagnosed with PMDD and had no history of any major affective disorder were included. The controls were women without PMDD matched for demographics and physical and psychiatric comorbidities. Cox regression was used to estimate the risk of unipolar depression and bipolar disorder. We included 8222 women with PMDD and 32,888 matched controls. After adjusting for potential confounders, we found that the women with PMDD were associated with a higher risk of unipolar depression [hazard ratio (HR) 2.58; 95 % confidence interval (CI), 2.23–2.98] and bipolar disorder (HR 2.50; 95 % CI 1.62–3.88) than the controls. The PMDD group had a younger age at the diagnosis of unipolar depression (37.11 vs 41.59 years) and bipolar disorder (35.59 vs 42.02 years, p = 0.002), and shorter duration between enrollment and onset of unipolar depression (2.97 vs 5.33 years, p < 0.001) and bipolar disorder (3.05 vs 5.57 years, p < 0.001). Our results showed a strong association between PMDD and major affective disorders. Healthcare workers should be aware of patients with PMDD and the risk of developing major affective mental disorders.

Contrasting genetic burden for bipolar disorder: early onset versus late onset in an older adults bipolar disorder (OABD) sample

Contrasting genetic burden for bipolar disorder: early onset versus late onset in an older adults bipolar disorder (OABD) sample

Risks of major affective disorders following a diagnosis of premenstrual dysphoric disorder: A nationwide longitudinal study.

Whether a history of premenstrual dysphoric disorder (PMDD) is associated with a subsequent risk of major affective disorders remains unclear. This study aimed to examine the risk of unipolar depression and bipolar disorder in women with PMDD compared with those without PMDD. This study used data from the Taiwan National Health Insurance Research Database. Women who were diagnosed with PMDD and had no history of any major affective disorder were included. The controls were women without PMDD matched for demographics and physical and psychiatric comorbidities. Cox regression was used to estimate the risk of unipolar depression and bipolar disorder. We included 8222 women with PMDD and 32,888 matched controls. After adjusting for potential confounders, we found that the women with PMDD were associated with a higher risk of unipolar depression [hazard ratio (HR) 2.58; 95% confidence interval (CI), 2.23-2.98] and bipolar disorder (HR 2.50; 95% CI 1.62-3.88) than the controls. The PMDD group had a younger age at the diagnosis of unipolar depression (37.11 vs 41.59 years) and bipolar disorder (35.59 vs 42.02 years, p=0.002), and shorter duration between enrollment and onset of unipolar depression (2.97 vs 5.33 years, p<0.001) and bipolar disorder (3.05 vs 5.57 years, p<0.001). Our results showed a strong association between PMDD and major affective disorders. Healthcare workers should be aware of patients with PMDD and the risk of developing major affective mental disorders.

Atypical Symptoms of Early Onset Bipolar Disorder

Juvenile bipolar disorder can be a challenging diagnosis, given its atypical presentation and tendency to have other comorbid psychiatric disorders. In this case study, we describe a case of a young patient with some atypical symptoms of early-onset bipolar disorder.

Course of subthreshold manic symptoms and related risk factors in the general population: A three-year follow-up study.

Subthreshold manic symptoms (subM) are a risk factor for the onset and recurrence of bipolar disorder (BD). Individuals with subM may benefit from preventive interventions, however, their development is hampered by a lack of knowledge on subM prevalence and subsequent course. This study examines subM characteristics, course, and risk factors for an unfavourable course. In a Dutch representative, population-based sample aged 18-64 (N= 4618), we assessed subM, defined as the occurrence of manic core symptoms (elation/irritability), without meeting full DSM-IV criteria for BD I or II in the past 3 years. Comparison groups had either no manic symptoms (noM) or hypomania/mania in the context of BD (mBD) in the past 3 years. Furthermore, we differentiated a mild and moderate type of subM, based on the number of manic symptoms. A subsequent three-year course was assessed prospectively. SubM had a three-year prevalence of 4.9%. Its prevalence, characteristics, and course were in between noM and mBD, and there were few differences between mild and moderate subM. Over the 3-year follow-up, 25.0% of individuals with subM had persistent subM and another 6.1% transitioned to mBD. Eleven significant risk factors for this unfavourable course were found. The most important were a history of depression/dysthymia (OR 3.75, p≤ 0.001), living alone (OR 2.61, p≤ 0.01) and elevated neuroticism score (OR 1.21, p≤ 0.001). This study supports the validity and clinical relevance of subM as a BD prodrome. It demonstrates that subM symptoms often persist or increase during follow-up and identifies 11 risk factors that are associated with an unfavourable course.

Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents.

Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endophenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hippocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder. Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n=41) and symptomatic offspring (SO) (n=39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up. We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left posterior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively). The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.

Clinical correlates of late-onset versus early-onset bipolar disorder in a global sample of older adults.

Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50years old) we aim to characterize the sociodemographic and clinical presentation of LOBD (≥40years at BD onset) compared to early-onset BD (EOBD: <40years at BD onset). The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data on 437 older age bipolar disorder participants. We compared LOBD versus EOBD on depression, mania, functionality, and physical comorbidities. Exploratory analyses were performed on participants with BD onset ≥50years old. LOBD (n=105) did not differ from EOBD (n=332) on depression, mania, global functioning, nor employment status (p>0.05). Late-onset bipolar disorder was associated with higher endocrine comorbidities (odds ratio=1.48, [95%CI=1.0,12.1], p=0.03). This difference did not remain significant when subjects with BD onset ≥50years old were analyzed. This study is limited by the retrospective nature of the variable age of onset and the differences in evaluation methods across studies (partially overcame by harmonization processes). The present analysis is in favor of the hypothesis that LOBD might represent a similar clinical phenotype as classic EOBD with respect to core BD symptomatology, functionality, and comorbid physical conditions. Large-scale global collaboration to improve our understanding of BD across the lifespan is needed.

The interplay of daily affect and impulsivity measured by mobile surveys in bipolar disorder

BackgroundImpulsivity is a prominent feature of bipolar disorder associated with various negative sequelae; moreover, it may be a precursor to shifts in affect or mood, but little is known about its association with affect on a day-to-day timescale. Ecological momentary assessments (a method that captures moment-to-moment ratings of psychological states by repeatedly sampling the same individual) of impulsivity and affect using mobile surveys allow for more nuanced examination of mechanisms of mood and behavior dysregulation. However, few existing studies have validated an ecological momentary assessment of impulsivity in bipolar disorder and examined its time-lagged associations with positive and negative affect. 70 participants with bipolar disorder and 102 healthy comparisons participated in an intensive longitudinal study: they underwent 14 days of ecological momentary assessment data collection annually for 1–4 years. Multiple measures of impulsivity and affect were collected using self-report, behavioral, and ecological momentary assessment modalities; these measures were compared, and levels of impulsivity were compared between bipolar disorder and healthy comparison groups. Time-lagged analyses using daily means explored the next-day predictive relationship of impulsivity on positive/negative affect, and vice versa.ResultsThe ecological momentary measure of impulsivity was moderately correlated with the self-report but not behavioral impulsivity measure. Bipolar disorder participants evinced higher self-report, behavioral, and daily impulsivity than healthy comparison participants. Time-lagged analyses revealed a bi-directional association between high impulsivity and high next-day negative (but not positive) affect. Post hoc analyses showed that impulsivity specifically predicted next-day anger and anxiety.ConclusionsOur multimodal assessment of impulsivity allowed for an examination of the day-to-day course of impulsivity and affect, crucial steps toward understanding the mechanisms of mood symptom and episode onset in bipolar disorder.

Adolescent cannabis use and the later onset of bipolar disorder: protocol for a systematic review and meta-analysis of prospective cohort studies.

Cannabis is used by adolescents worldwide. Adolescents are more susceptible to the psychological effects of cannabis because their brains are still developing. Cannabis use in adolescents has been reportedly associated with later onset of bipolar disorder. The purpose of this study is to systematically review and analyze longitudinal prospective cohort studies of cannabis use during adolescence and evaluate the risk of developing bipolar disorder. We defined the participants, exposures, comparisons, and outcomes (PECO) as follows: (P) adolescents in the 10-19-year age group at the baseline survey; (E) cannabis use at least once during lifetime; (C) never-used cannabis over lifetime; and (O) the onset of bipolar disorder. A systematic search for published prospective cohort studies will be conducted by using the following electronic databases: PubMed, EMBASE, PsycINFO, and Japan Medical Abstracts Society. The quality assessment will be performed by using Risk Of Bias In Non-randomized Studies - of Interventions. Meta-analysis will be done if the included studies that exist are more than three. Heterogeneity will be assessed using Cochran's Q test and I2 . Funnel plots and Egger's test will be done to assess publication bias. This study will clarify the association between adolescent cannabis use and the subsequent development of bipolar disorder, which could be useful for future research directions and policy making.

High incidence of PTSD diagnosis and trauma-related symptoms in a trauma exposed bipolar I and II sample.

Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (https://clinicaltrials.gov; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients.

Mood Instability in Youth at High Risk for Bipolar Disorder.

Mood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD, we examined the association between mood instability and symptomatic, psychosocial, and familial functioning over an average of 2 years. Youth (aged 9-17 years) with major depressive disorder or other specified BD, current mood symptoms, and a family history of BD were rated by parents on a mood instability scale. Participants were randomly assigned to 4 months of family-focused therapy or enhanced care psychoeducation, both with medication management as needed. Independent evaluators rated youth every 4-6 months for up to 4 years on symptom severity and psychosocial functioning, whereas parents rated mood instability of the youth and levels of family conflict. High-risk youth (N= 114; mean age 13.3 ± 2.6 years; 72 female) were followed for an average of 104.3 ± 65.8 weeks (range, 0-255 weeks) after randomization. Youth with other specified BD (vs major depressive disorder), younger age, earlier symptom onset, more severe mood symptoms, lower psychosocial functioning, and more familial conflict over time had higher mood instability ratings throughout the study period. Mood instability mediated the association between baseline diagnosis and mother/offspring conflict at follow-up (Z= 2.88, p= .004, αβ= 0.19, 95% CI= 0.06-0.32). Psychosocial interventions did not moderate these associations. A questionnaire measure of mood instability tracked closely with symptomatic, psychosocial, and family functioning in youth at high risk for BD. Interventions that are successful in reducing mood instability may enhance long-term outcomes among high-risk youth. Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

25.2 41030: Risk Factors of Mood Disorders and Predictors of the Conversion From MDD to Bipolar Disorders in a Prospective High-Risk Cohort Study

Using prospective data on the offspring of patients with unipolar and bipolar mood disorders as well as clinical controls, our aims were to identify the risk factors for: 1) the onset of bipolar disorder (BPD) and MDD; and 2) conversion from MDD to BPD.