Onset Of Bipolar Disorder Research Articles

A customized adherence enhancement program for adolescents and young adults with suboptimal adherence and bipolar disorder: Trial design and methodological report

BackgroundThe onset of bipolar disorder (BD) is common during late adolescence and young adulthood (AYA). Suboptimal medication adherence is a critical yet modifiable risk factor for negative outcomes among AYAs with BD. MethodsThis research used an iterative process (e.g., focus groups, advisory board, cognitive interviews) to modify an existing adherence intervention to address suboptimal adherence in AYAs with BD. The modified version of Customized Adherence Enhancement for Adolescents and Young Adults (CAE-AYA) will be compared to an Enhanced Treatment as Usual condition (ETAU) in 40 AYAs intervention using a 6-month prospective, randomized controlled trial (RCT) in a high-risk group of 16–21 year old AYAs with BD with demonstrated non-adherence to their prescribed BD medications. ConclusionsThis report describes the methodology and design of the ImprovinG adhereNce In adolescenTs with bipolar disordEr (IGNITE) study. If successful, the CAE-AYA approach has the potential to advance care for vulnerable youth with BD.

Bipolar spectrum disorders are associated with increased gray matter volume in the medial orbitofrontal cortex and nucleus accumbens.

Elevated sensitivity to rewards prospectively predicts Bipolar Spectrum Disorder (BSD) onset; however, it is unclear whether volumetric abnormalities also reflect BSD risk. BSDs emerge when critical neurodevelopment in frontal and striatal regions occurs in sex-specific ways. The current paper examined the volume of frontal and striatal brain regions in both individuals with and at risk for a BSD with exploratory analyses examining sex-specificity. One hundred fourteen medication-free individuals ages 18-27 at low-risk for BSD (moderate-reward sensitivity; N = 37), at high-risk without a BSD (high-reward sensitivity; N = 47), or with a BSD (N = 30) completed a structural MRI scan of the brain. We examined group differences in gray matter volume in a priori medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAcc) regions-of-interest. The BSD group had enlarged frontostriatal volumes (mOFC, NAcc) compared to low individuals (d = 1.01). The mOFC volume in BSD was larger than low-risk (d = 1.01) and the high-risk groups (d = 0.74). This effect was driven by males with a BSD, who showed an enlarged mOFC compared to low (d = 1.01) and high-risk males (d = 0.74). Males with a BSD also showed a greater NAcc volume compared to males at low-risk (d = 0.49), but not high-risk males. An enlarged frontostriatal volume (averaged mOFC, NAcc) is associated with the presence of a BSD, while subvolumes (mOFC vs. NAcc) showed unique patterning in relation to risk. We report preliminary evidence that sex moderates frontostriatal volume in BSD, highlighting the need for larger longitudinal risk studies examining the role of sex-specific neurodevelopmental trajectories in emerging BSDs.

Depressive and Anxious Temperaments as Predictors of Late Onset Bipolar Disorder? Preliminary Results of a "Real World" Exploratory Study.

IntroductionBipolar disorder (BD) onset typically occurs between 15 and 30 years, being diagnosed under the age of 50 in 90% of cases, named “non-late onset BD” (non-LOBD). However, clinical observation of late-onset BD (LOBD) raised some concern regarding a differential psychopathological pattern, outcomes and treatment, including a specific affective temperament vulnerability. Therefore, an exploratory study in the “real world” was carried out by investigating psychopathological and temperamental features of a psychogeriatric cohort of LOBD and non-LOBD subjects.MethodsA total of 180 patients affected with BD-I, BD-II, and Cyclothymic Disorder were screened in a Mood Disorder Outpatient Service, during the timeframe January 2019-August 2021. Out of 78 enrolled outpatients, 66 (33 non-LOBD, 33 LOBD) were recruited, by the retrospective collection of sociodemographic, cognitive, psychopathological and clinical assessment, including the short-version of the Temperament Evaluation of Memphis, Pisa, and San Diego (TEMPS-M).ResultsLOBD is significantly associated with higher rates of BD-II diagnosis (χ2 = 27.692, p < 0.001), depressive episodes (p = 0.025), mixed states (p = 0.009), predominant depressive and anxious affective temperaments (p < 0.001). Non-LOBD is significantly associated with higher endocrinological (χ2 = 6.988, p = 0.008) and metabolic comorbidity (χ2 = 5.987, p = 0.014), a diagnosis of BD-I, manic episodes, and predominant hyperthymic affective temperaments (p = 0.001). GDS (p < 0.001) and MSRS (p = 0.005) scores were significantly higher in LOBD.ConclusionFurther longitudinal studies with larger sample sizes and a control group are needed to determine whether LOBD may represent a distinct psychopathological entity from non-LOBD and evaluate differences (if any) in terms of prognosis and treatment between non-LOBD and LOBD.

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress-Induced Damage in Patients with Bipolar Disorder.

Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

A comparison of symptoms of bipolar and unipolar depression in postpartum women

BackgroundDistinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders. MethodsWe performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4–6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS). ResultsThe sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse. LimitationsOnly women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data. ConclusionsSeverity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.

Metabolomic Identification of Serum Exosome-Derived Biomarkers for Bipolar Disorder.

Background Exosomes are extracellular vesicles that play important roles in various physiological and pathological functions. Previous studies have demonstrated that exosome-derived contents are promising biomarkers to inform the pathogenesis and diagnosis of major depressive disorder and schizophrenia. Methods We used ultraperformance liquid chromatography-tandem mass spectrometry to analyze the differentially expressed metabolites in serum exosomes of patients with bipolar disorder (BD) and evaluated the potential of exosomal metabolites as biomarkers for BD. Results Our results showed 26 differentially expressed serum exosomal metabolites in patients with BD (n = 32) when compared with healthy control (HC) subjects (n = 40), and these differentially expressed metabolites were enriched in pathways related to sugar metabolism. We then utilized random forest classifier and identified 15 exosomal metabolites that can be used to classify samples from patients with BD and HC subjects with 0.838 accuracy (95% CI, 0.604–1.00) in the training set of participants. These 15 metabolites showed excellent performance in differentiating between patients with BD and HC subjects in the testing set of participants, with 0.971 accuracy (95% CI, 0.865–1.00). Importantly, the 15 exosomal metabolites also showed good to excellent performance in differentiating between BD patients and other major psychiatric diseases (major depressive disorder and schizophrenia). Conclusion Collectively, our findings for the first time revealed a potential role of exosomal metabolite dysregulations in the onset and/or development of BD and suggested that blood exosomal metabolites are strong candidates to inform the diagnosis of BD.

Prof K C Dube Poster Award

Objective-1. To assess the clinical characteristics of late onset bipolar disorder and to compare with adult onset bipolar disorder and 2. To compare the medical co morbidity between age, sex matched healthy control group.Material & method– It was a hospital based, observational, analytical and cross-sectional study conducted in department of Psychiatry in a tertiary care centre. The patients > 60 years presenting with manic features after satisfying the inclusion and exclusion criteria were included in the study group. Control group -1 was selected from patients of adult onset bipolar disorder. YMRS, MMSE were applied for participants in all the groups. Control group -2 was selected from age, sex, education matched normal population and the three groups were compared for co morbidity. Secondary mania cases are excluded from the study.Results– Mean age at onset in the study group was 67.4 years. 63.3% of our patients were female. H/O psychiatric illness in family was more in the control group 1 (53.3%) than in study group (26.7%) (p=0.035). while studying the clinical characteristics, it was found that 86.6% patients in the study group presented with irritability, 73.3% patients were presented with aggression. Whereas in the control group 1 irritability was found in 90%, aggression75%. The difference is not statistically significant. However, the scoring of each symptom showed significant difference. It means presence & severity of delusion is significantly more in young bipolar control group. (p=0.035 for % score, p=0.015 for mean SAPS score). 70% presented with co morbidities.Conclusion– Geriatric mania shows mixed presentation compared to early onset disease. Psychotic features are more common. Late onset mania is less associated with family history. Common co morbidities are DM, HTN, Hypothyroidism, neurologic disorders.

Association of Sociocultural Stressors with Bipolar Disorder Onset in Puerto Rican Youth Growing Up as Members of a Minoritized Ethnic Group: Results from the Boricua Youth Longitudinal Study

Association of Sociocultural Stressors with Bipolar Disorder Onset in Puerto Rican Youth Growing Up as Members of a Minoritized Ethnic Group: Results from the Boricua Youth Longitudinal Study

Factors Associated with Age of Onset of Bipolar Affective Disorder from a Tertiary Care Hospital in Southern India: A Cross-sectional Study

Introduction: Bipolar Affective Disorder (BPAD), is a chronic debilitating disorder. The mean age at onset for BPAD is observed to be around 20-30 years. The Age at Onset (AO) of BPAD is affected by various factors, including gender, family history, substance use, and other environmental factors. Aim: To assess the AO of BPAD in the clinical population and the relationship of socio-demographic and clinical factors with AO. Materials and Methods: A cross-sectional study, was conducted at Department of Psychiatry, Chettinad Hospital and Research Institute, Kelambakkam, Tamil Nadu, India, from January 2020 to January 2021. The socio-demographic details of total of 53 participants suffering from BPAD attending the tertiary care psychiatric setting were collected. The AO of the sample data and its correlation with gender, family history, substance use, marital status, residential background, etc was analysed by using Statistical Package for the Social Sciences (SPSS) version 22.0. Independent t-test and Analysis of Variance (ANOVA) were applied to compare AO among different variables. Pearson’s correlation and multiple linear regression were applied to assess the correlation. Results: Out of the 53 participants, 30 participants (56.6%) were males and 23 (43.4%) were females of which 31 (58.5%) of the participants had a family history of psychiatric illness. Eighteen (33.8%) had some substance use before onset. No substance use was reported by females. The mean AO of the sample was 24±7.8 years. The mean AO was significantly earlier for, males (t= -2.598; p=0.012), those with a family history of psychiatric illness (t=968; p&lt;0.01) and urban dwellers (t=-3.752; p&lt;0.01). Multiple linear regression analysis showed only family history (B=-3.07, p=0.01) and urban background (B=3.60, p=0.01) significantly predicted earlier AO. AO also negatively correlated with number of suicides per person years of illness (r= -0.387; p&lt;0.01), and number of episodes per person years of illness (r=-0.322, p=0.01). Conclusion: Presence of a family history of psychiatric illness and residing in urban areas showed an overall early prediction of AO rather than gender, and other environmental factors. Earlier AO was associated with worse clinical outcomes of BPAD. Knowledge about AO and its factors might help in predicting treatment outcomes, and in planning primary preventive strategies for vulnerable populations.

Abstract- Poster

Background:Lithium continues to be one of first-line prophylactic agents for bipolar disorder (BD) but only about one-third of patients are excellent responders. Studies have described various clinical correlates of treatment response but Indian literature is limited.Aim:to assess the relationship of clinical variables to lithium response in subjects with BD on long-term prophylaxisMethodology:This was a cross-sectional, observational study of 40 subjects, aged 18-60 years, with DSM-5 BD type I, currently in remission. Subjects were included if they were on regular and long-term lithium for atleast one year or more. All subjects were screened using MINI 7.0 to exclude co morbidities and standard scales (YMRS≤4, HAM-D<8) to establish euthymia. Subjects were assessed using clinical proforma, NIMH Life Chart Method, Alda Lithium Response Scale (LRS) and IGSLI scale for typical/atypical features.Results:Mean age for sample was 38.28 ±10.41 years (72.5% males). Mean illness duration was 13.84±9.23 years, with average onset at 24.40±8.21 years. Mean duration on lithium was 5.49±4.11 years (1-18 years) The LRS total (A-B) score showed a significant positive correlation to IGSLI typical features score (p=0.003), time since remission (p=0.034) and a significant negative correlation to IGSLI atypical features score (p=0.019) and age of onset of BD (p=0.037). There was a trend towards poorer lithium response with higher BMI (p=0.052)Conclusion:The clinical course characterized by an early age of onset and more atypical features (via. more manic than depressive episodes, presence of residual symptoms, mood incongruent psychotic features) appear to respond poorer to lithium.

Course and outcome of bipolar I disorder among Indian patients: A retrospective life-chart study.

Indian studies on the course and outcome of bipolar disorder (BD) are scarce and their methodologies vary. Nevertheless, differences from Western ones have been noted. A systematic random sample of 200 patients with BD attending a general hospital psychiatric unit was chosen. They were assessed using the clinician and self-rated versions of the National Institute of Mental Health-Retrospective Life Charts, the lifetime version of the Columbia Suicide Severity Rating Scale, the Medication Adherence Questionnaire, the Indian Disability Evaluation and Assessment Scale, and the Presumptive Stressful Life Events Scale. The mean age of onset of BD was 26 years. About 11%-13% of the illness was spent in acute episodes, mostly in depression (60%). Episode frequency was 0.4-0.6 annually. The first episode was more likely to be manic, and manic episodes outnumbered depressive episodes. The average duration of episodes was 3 months. Depressive episodes were longer and the time spent in depression was greater than mania. Psychotic symptoms (48%), a mania-depression-interval pattern (61%), and recurrent mania (19%) were common while rapid cycling and seasonal patterns were uncommon. Comorbidity (40%), functional impairment (77%), and lifetime nonadherence (58%) were high, whereas lifetime suicide attempts (16%) were low. Stressful life events were very common prior to episodes (80%), particularly early in the illness. This study suggests differences between Indian and Western patients in the demographic profile and the course and outcome of BD. A more benign presentation in the current study including Indian studies is indicated by their later age of presentation and illness onset, higher rates of marriage, education, and employment, a mania predominant course, lower rates of rapid cycling, comorbidity, and suicidal attempts. Factors associated with better outcomes such as longer time to recurrence, Manic Depressive pattern of illness, and low rates of hospitalizations also appear to be commoner in our study and also in other Indian studies.

Abstract- Poster

Background:Lithium continues to be one of first-line prophylactic agents for bipolar disorder (BD) but only about one-third of patients are excellent responders. Studies have described various clinical correlates of treatment response but Indian literature is limited.Aim:to assess the relationship of clinical variables to lithium response in subjects with BD on long-term prophylaxisMethodology:This was a cross-sectional, observational study of 40 subjects, aged 18-60 years, with DSM-5 BD type I, currently in remission. Subjects were included if they were on regular and long-term lithium for atleast one year or more. All subjects were screened using MINI 7.0 to exclude co morbidities and standard scales (YMRS≤4, HAM-D<8) to establish euthymia. Subjects were assessed using clinical proforma, NIMH Life Chart Method, Alda Lithium Response Scale (LRS) and IGSLI scale for typical/atypical features.Results:Mean age for sample was 38.28 ±10.41 years (72.5% males). Mean illness duration was 13.84±9.23 years, with average onset at 24.40±8.21 years. Mean duration on lithium was 5.49±4.11 years (1-18 years) The LRS total (A-B) score showed a significant positive correlation to IGSLI typical features score (p=0.003), time since remission (p=0.034) and a significant negative correlation to IGSLI atypical features score (p=0.019) and age of onset of BD (p=0.037). There was a trend towards poorer lithium response with higher BMI (p=0.052)Conclusion:The clinical course characterized by an early age of onset and more atypical features (via. more manic than depressive episodes, presence of residual symptoms, mood incongruent psychotic features) appear to respond poorer to lithium.

Influence of childhood maltreatment on prevalence, onset, and persistence of psychiatric comorbidities and suicide attempts in bipolar disorders.

Psychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms. We assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses. Psychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD=1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts. Childhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality.

Constrictive Entrapment Neuropathies of a Limb Secondary to Restraint Strapping: A Case Report

Rationale: Entrapment neuropathies are peripheral nerve disorders at specific anatomical locations. They may be caused by trauma in a manner of sprains or bone fracture, but it is often caused by repetitive insults or compression of nerves as they travel through a narrow anatomic space. Pregnancy and pre-existing comorbidities such as diabetes, obesity, cancer, or autoimmune diseases may also cause nerve entrapment. Objective: To highlight the case of a 52-year-old female developing right foot dysesthesia and weakness after continuous restraint strapping from her previous hospitalization. Case: Here we have the case of a 52-year-old Filipino female consulted because of right foot dysesthesia, allodynia, and mild weakness. She had a history of bipolar disorder and recent onset of acute psychosis and overdosing with her irregularly taken maintenance olanzapine tablets. She was put on restraint strapping of the right lower limb in her one-week hospital stay. This resulted in developing restraint marks on her right ankle accompanied by difficulty walking on heels and toes, spontaneous dysesthesia, and touch allodynia of her entire right foot. An electrodiagnosis yielded right lower limb focal neuropathies involving the right fibular nerve, right tibial nerve, right superficial fibular, and right sural nerves. The prescribed amitriptyline and gabapentin for 6 months led to gradual improvement of neuropathic pain. Discussion and Summary: Our case exemplifies focal limb neuropathies from entrapment due to restraint strapping. Electrodiagnostic confirmation of neuropathies of the same limb sensory and motor nerves was mandated to corroborate clinical neuropathic pain and after ruling out other causes of entrapment neuropathies. Prolonged use of neuropathic pain medications were needed to attain relief in this present case. Restrictive strapping is an iatrogenic cause of entrapment neuropathy that is preventable, had there been proper medical attention applied.

Role of Polygenic Risk Score in the Familial Transmission of Bipolar Disorder in Youth

Establishing genetic contributions to the transmission of bipolar disorder (BD) from parents to offspring may inform the risk of developing this disorder and further serve to validate BD in youth. To evaluate the specific association of BD polygenic risk scores (PRSs) on the familial transmission and validity of pediatric BD. This community-based case-control longitudinal study (Pittsburgh Biological Offspring Study) included parents with BD I/II and their offspring and parents without BD (healthy or non-BD psychopathology) and their offspring. Participants were recruited between March 2001 and May 2007, and analysis took place from December 2020 to September 2021. PRSs for BD, major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder. Participants were prospectively evaluated using standardized interviews blind to parental diagnosis. DNA was extracted from saliva and genotyped. PRSs were constructed based on independent large-scale genome-wide association studies. A total of 156 parents with BD I/II and 180 parents without BD (mean [SD] age, 39.6 [7.9] years; 241 female [72%]) as well as 251 offspring of parents with BD and 158 offspring of parents without BD (mean [SD] age, 10.4 [4.7] years; 213 female [52%]) of European ancestry were analyzed. Participants were assessed a mean of 6.7 times during a mean (SD) of 13 (3.4) years of follow-up (84% retention). More offspring of parents with BD developed BD (58 [23.1%] vs 8 [5.1%]; P < .001) and depression (126 [50.2%] vs 52 [32.9%]; P < .001) compared with offspring of parents without BD. BD PRS was higher in both parents and offspring with BD than parents and offspring without BD (parents: odds ratio, 1.50; 95% CI, 1.19-1.89; P < .001; explained 4.8% of the phenotypic variance vs offspring: hazard ratio, 1.34; 95% CI, 1.03-1.7; P = .02; explained 5.0% of the phenotypic variance). BD PRS did not differ across BD subtypes. In a model combining parental and offspring BD PRS, the parental BD PRS association with offspring BD was fully mediated by offspring BD PRS (hazard ratio, 1.40; 95% CI, 1.05-1.86; P = .02). Parental BD had a stronger direct association than parental or offspring BD PRS with offspring BD risk (hazard ratio, 5.21; 95% CI, 1.86-14.62; P = .002), explaining 30% of the variance. Parental and offspring BD PRS explained 6% of the BD onset variance beyond parental diagnosis. There were no significant between-group differences in PRSs for major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder in parents or offspring and they were not significantly associated with BD onset. The findings of this study add to the extant clinical validation of BD in youth. Parental BD and offspring BD PRS independently associated with the risk of BD in offspring. Although this is promising, the association of BD PRS was relatively small and cannot be used alone to determine BD risk until further developments occur.

Association of Etiological Factors for Hypomanic Symptoms, Bipolar Disorder, and Other Severe Mental Illnesses

Subsyndromal hypomanic symptoms are relatively common in the general population and are linked to the onset of bipolar disorder. Little is known about their etiology and whether this is shared with the etiology of bipolar disorder or other mental illnesses. To examine the genetic and environmental architecture of hypomanic symptoms in a nonclinical youth sample and compare estimates at varying severity levels and their association with diagnosed bipolar disorder. This cohort study used phenotypic and genetic data from the Child and Adolescent Twin Study in Sweden and included individuals with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis of psychiatric disorders from national registries for residents of Sweden. Associations between hypomania and polygenic risk scores for bipolar disorder, major depressive disorder and schizophrenia were also investigated. Analysis began November 2018 and ended October 2021. Hypomanic symptoms were assessed using the parent-rated Mood Disorders Questionnaire when the twins were aged 18 years. Bipolar disorder diagnosis and/or lithium prescription were ascertained from national registries for residents of Sweden. Polygenic risk scores for psychiatric disorders were calculated using independent discovery genetic data. A total of 8568 twin pairs aged 18 years (9381 [54.7%] female) were included in the study. The hypomania heritability estimate was 59% (95% CI, 52%-64%) for male individuals and 29% (95% CI, 16%-44%) for female individuals. Unique environmental factors accounted for 41% (95% CI, 36%-47%) of the hypomania variance in male individuals and 45% (95% CI, 40%-50%) in female individuals. Shared environmental factors were only detected for female individuals and explained 26% (95% CI, 13%-38%) of the variance. The heritability estimates were fairly consistent across different hypomania severity groups. Moderate genetic (0.40; 95% CI, 0.21-0.58) and shared environmental (0.41; 95% CI, 0.03-0.75) correlations between hypomania and diagnosed bipolar disorder were found. Hypomania was significantly associated with the polygenic risk scores for schizophrenia (β = 0.08; SE = 0.026; P = .002) and major depressive disorder (β = 0.09; SE = 0.027; P = .001) but not bipolar disorder (β = 0.017; SE = 0.03; P = 0.57) (bipolar disorder I [β = 0.014; SE = 0.029; P = .64] or bipolar disorder II [β = 0.045; SE = 0.027; P = .10]). Higher heritability for hypomania was found for male compared with female individuals. The results highlight the shared etiologies between hypomanic symptoms, bipolar disorder, major depression, and schizophrenia in youths. Future research should focus on identifying specific shared genetic and environmental factors. These findings support a possible dimensional model of bipolar disorder, with hypomania representing a continuous trait underlying the disorder.

Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence.

Cannabis use among people with mood disorders increased in recent years. While comorbidity between cannabis use, cannabis use disorder (CUD), and mood disorders is high, the underlying mechanisms remain unclear. We aimed to evaluate (1) the epidemiological evidence for an association between cannabis use, CUD, and mood disorders; (2) prospective longitudinal, genetic, and neurocognitive evidence of underlying mechanisms; and (3) prognosis and treatment options for individuals with CUD and mood disorders. Narrative review of existing literature is identified through PubMed searches, reviews, and meta-analyses. Evidence was reviewed separately for depression, bipolar disorder, and suicide. Current evidence is limited and mixed but suggestive of a bidirectional relationship between cannabis use, CUD, and the onset of depression. The evidence more consistently points to cannabis use preceding onset of bipolar disorder. Shared neurocognitive mechanisms and underlying genetic and environmental risk factors appear to explain part of the association. However, cannabis use itself may also influence the development of mood disorders, while others may initiate cannabis use to self-medicate symptoms. Comorbid cannabis use and CUD are associated with worse prognosis for depression and bipolar disorder including increased suicidal behaviors. Evidence for targeted treatments is limited. The current evidence base is limited by the lack of well-controlled prospective longitudinal studies and clinical studies including comorbid individuals. Future studies in humans examining the causal pathways and potential mechanisms of the association between cannabis use, CUD, and mood disorder comorbidity are crucial for optimizing harm reduction and treatment strategies.

A commentary on youth onset bipolar disorder.

Given ongoing disagreement about the diagnosis of pediatric bipolar disorder, we sought to illuminate key empirical findings regarding the condition in children and adolescents. We conducted a review of extant studies of the diagnosis, course, and treatment of bipolar disorder in children and adolescents. Bipolar disorder is a lifelong, familial condition with frequent onset in childhood or adolescence. Secular trends indicate that globally, the onset of puberty is occurring earlier, which may contribute to increased identification of mood disorders in younger populations. Despite opinions to the contrary, bipolar disorder has been observed in youth around the world, not just in the U.S. Discrete and episodic manic symptoms occur on a continuum/spectrum of severity and duration. Clinicians may be just as likely to miss mania (false negatives) as overcall it (false positives). As is true in adults, periodicity and heterogeneity are defining features of early onset bipolar disorder. Youth who are misdiagnosed and undiagnosed tend to do poorly over the long term. Youth with and at risk for bipolar disorder are frequently exposed to maltreatment, abuse, and bullying. Fortunately, there are now many evidence-based interventions that have been studied in thousands of youth with or at high risk for bipolar disorder, demonstrating large effect sizes for evaluated treatments versus comparative treatments. Identifying optimal methods for the evaluation and treatment of bipolar disorder in children and adolescents represents important advances in the field. Recognizing the occurrence of mania symptoms in youth is pivotal for improving outcomes in patients living with bipolar disorder.

Bipolar Type I Disorder in Children

Bipolar disorder in children and adolescents is a clinical disorder that causes publicmental health problems that need attention. In the last decade, bipolar disorder inchildren and adolescents has become a trendy field, both in the clinical area and inresearch, especially in terms of diagnosis, which is still controversial. The controversythat remains is whether it is possible to diagnose bipolar disorder in prepubertalchildren. Based on the DSM-IV-TR diagnostic criteria, the prevalence of the bipolardisorder in children scarce rare. Epidemiological studies report the lifetimeprevalence of bipolar I and II disorders in late adolescence is about 1 per cent. Variousstudies in a large population have shown a prevalence rate of 0.1% -2%. The onsetof bipolar disorder in children and adolescents is often accompanied by a more severedisease course, compared to bipolar disorder with onset in adulthood. This casereport presents a case of bipolar 1 in children accompanied by comprehensivemanagement.

Using density of antecedent events and trajectory path analysis to investigate family-correlated patterns of onset of bipolar I disorder: a comparison of cohorts from Europe and USA

BackgroundMajor contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I.MethodsFirst, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R2 goodness of fit analysis).ResultsEarlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R2 analysis was significantly different for the European cohort only.ConclusionsEstimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.