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Background: Anticipating diagnostic change from major depressive (MDD) to bipolar disorder (BD) can support better prognosis and treatment, especially of depression but is challenging and reported research results are inconsistent. We therefore assessed clinical characteristics associated with diagnostic change from MDD to BD with antidepressant treatments. Methods: We compared characteristics of 3212 initially MDD patients who became (hypo)manic during antidepressant treatment to those with stable MDD diagnoses as well as with cases of stable, spontaneous BD, using standard bivariate and multivariate statistics. Results: Among MDD patients, 6.69% [CI: 5.85–7.61] changed to BD, mostly type II (BD2, 76.7%). BD‐converters had higher rates of familial mood disorders (74.1% vs. 57.1%) or BD (33.7% vs. 21.0%) and 2.8‐years younger onset than stable MDD patients. They also had more prior depressive recurrences/year, years‐of‐illness, mood‐stabilizer treatment, divorces, fewer children, more suicide attempts and drug‐abuse, and higher intake cyclothymia, YMRS and MDQ scores. Predictors independently associated with diagnostic conversion were: more familial BD, depressions/year, unemployment, cyclothymic temperament, suicidal ideation or acts, and fewer children. BD‐converters vs. spontaneous BD cases had significantly more suicide attempts, BD2 diagnoses, and affected relatives. Converting to vs. spontaneous BD1 was associated with more ADHD, more suicidal ideation or behavior, MDI course, and younger onset; converting to vs. spontaneous BD2 had more episodes/year, unemployment, ADHD, substance abuse, suicidal ideation or attempts, and more relatives with BD. Conclusions: Few (6.69%) initially MDD subjects converted to BD, most (76.7%) to BD2. Independent predictive associations with diagnostic change included: familial BD, more depressions/year, unemployment, cyclothymic temperament, suicidal behavior and fewer children. Notably, several characteristics were stronger among those changing to BD during antidepressant treatment vs. others with spontaneous BD. [ABSTRACT FROM AUTHOR]

Background: Rapid-cycling (RC; ≥ 4 episodes/year) in bipolar disorder (BD) has been recognized since the 1970s and associated with inferior treatment response. However, associations of single years of RC with overall cycling rate, long-term morbidity, and diagnostic subtypes are not clear. Results: We compared descriptive and clinical characteristics in 1261 BD patients with/without RC, based on history and prospective follow-up for several years. RC in any previous year was identified in 9.36% of BD subjects (3.74% in BD1, 15.2% BD2), and somewhat more among women than men. RC-BD subjects had 3.21-fold greater average prospective annual rates of recurrence but not hospitalizations, had less difference in %-time-ill, received more mood-stabilizing treatments, and had greater suicidal risk, lacked familial psychiatric illnesses, had more cyclothymic temperament, were more likely to be married, had more siblings and children, experienced early sexual abuse, but were less likely to abuse drugs (not alcohol) or smoke. In multivariable regression modeling, older age, mood-switching with antidepressants, and BD2 > BD1 diagnosis, as well as more episodes/year were independently associated with RC. Notably, prospective mean recurrence rates were below 4/year in 79.5% of previously RC patients, and below 2/year in 48.1%. Conclusions: Lifetime risk of RC in BD was 9.36%, more likely in women, with older age, and in BD2 > BD1. With RC, recurrence rates were much higher, especially for depression with less effect on %-time ill, suggesting shorter episodes. Variable associations with unfavorable outcomes and prospective recurrence rates well below 4/year in most previously RC patients indicate that RC was not a sustained characteristic and probably was associated with use of antidepressants. [ABSTRACT FROM AUTHOR]

Objective: Compare patients diagnosed as DSM-5 type II bipolar disorder (BD2) vs. major depressive disorder (MDD).Methods: We compared characteristics of 3246 closely and repeatedly evaluated, consenting, adult patient-subjects (n = 706 BD2, 2540 MDD) at a specialty clinic using bivariate methods and multivariable modeling.Results: Factors more associated with BD2 than MDD included: [a] descriptors (more familial psychiatric, mood and bipolar disorders and suicide; younger at onset, diagnosis and first-treatment; more education; more unemployment; fewer marriages and children; higher cyclothymic, hyperthymic and irritable temperament ratings, lower anxious); [b] morbidity (more hypomanic, mixed or panic first episodes; more co-occurring general medical diagnoses, more Cluster B personality disorder diagnoses and ADHD; more alcohol and drug abuse and smoking; shorter depressive episodes and interepisode periods; lower intake ratings of depression and anxiety, higher for hypomania; far more mood-switching with antidepressants; lower %-time depressed; DMI > MDI course-pattern in BD2; more suicide attempts and violent suicidal behavior); [c] item-scores with intake HDRS21 higher for suicidality, paranoia, anhedonia, guilt, and circadian variation; lower somatic anxiety, depressed mood, insight, hypochondriasis, agitation, and insomnia; and [d] treatment (more lithium, mood-stabilizing anticonvulsants and antipsychotics, less antidepressants and benzodiazepines).Conclusions: BD2 and MDD subjects differed greatly in many descriptive, psychopathological and treatment measures, notably including more familial risk, earlier onset, more frequent recurrences and greater suicidal risk with BD2. Such differences can contribute to improving differentiation of the disorders and planning for their treatment. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses., Method: We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications., Results: Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD., Conclusions: The proposed NDP constitutes a promising clinical tool for patient stratification in BD., (Copyright © 2024. Published by Elsevier Inc.)