Family History Of Bipolar Disorder Research Articles

Bipolar disorders following initial depression: Modeling predictive clinical factors

ObjectiveMost first lifetime episodes among persons eventually diagnosed with bipolar disorder are depressive, often with years of delay to a final differentiation from unipolar major depression. To support early differentiation, we tested several predictive factors for association with later diagnoses of bipolar disorder. MethodWith data from mood-disorder patients with first-lifetime episodes of major depression, we used multivariate, logistic modeling and Bayesian methods including Receiver Operating Characteristic curves to evaluate ability of one or more selected factors to differentiate patients who later met DSM-IV-TR diagnostic criteria for bipolar disorder and not unipolar major depressive disorder. ResultsWe analyzed data from 2146 patients (642 bipolar, 1504 unipolar) at risk for 13 years following initial depressive episodes. In multivariate modeling for 812 subjects with information on all clinical factors considered, seven significantly and independently differentiated bipolar from unipolar disorders, ranking (by significance): (a) ≥4 previous depressive episodes, (b) suicidal acts, (c) cyclothymic temperament, (d) family history of bipolar disorder, (e) substance-abuse, (f) younger-at-onset, or onset-age <25, and (g) male sex; four of these (c, d, f, g) can be identified at illness-onset. Bayesian analysis indicated optimal sensitivity and specificity at 2–4 factors/person and correct classification of 64–67% of cases, and ROC analysis of factors/person yielded a significant area-under-the-curve of 0.72 [CI: 0.68–0.75]. ConclusionsIn multivariate modeling, 7 factors were significantly and independently associated with bipolar disorder diagnosed up to 13 years after initial depression.

Differences between patients with borderline personality disorder who do and do not have a family history of bipolar disorder

Diagnostic confusion sometimes exists between bipolar disorder and borderline personality disorder (BPD). To improve the recognition of bipolar disorder researchers have identified nondiagnostic factors that point toward bipolar disorder. One such factor is the presence of a family history of bipolar disorder. In the current report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we compared the demographic, clinical, and psychosocial characteristics of patients with BPD who did and did not have a family history of bipolar disorder. A large sample of psychiatric outpatients were interviewed with semi-structured interviews. Three hundred seventeen patients without bipolar disorder were diagnosed with DSM-IV borderline personality disorder. Slightly less than 10% of the 317 patients with BPD (9.5%, n=30) reported a family history of bipolar disorder in their first-degree relatives. There were no differences between groups in any specific Axis I or Axis II disorder. The patients with a positive family history were significantly less likely to report excessive or inappropriate anger, but there was no difference in the frequency of other criteria for BPD such as affective instability, impulsivity, or suicidal behavior. The patients with a positive family history reported a significantly higher rate of increased appetite and fatigue. There was no difference in overall severity of depression, scores on the Global Assessment of Functioning, history of psychiatric hospitalizations, suicide attempts, time unemployed due to psychiatric reasons during the 5years before the evaluation, and ratings of current and adolescent social functioning. There was no difference on any of the 5 subscales of the childhood trauma questionnaire. Overall, we found few differences between BPD patients with and without a family history of bipolar disorder thereby suggesting that a positive family history of bipolar disorder was not a useful marker for occult bipolar disorder in these patients.

Misdiagnosis of Bipolar Depression in Primary Care Practices

Misdiagnosis of bipolar disorder is too frequent in primary care practices. Early diagnosis of the disease is crucial for appropriate treatment and optimal outcomes, yet patients may go years without a proper diagnosis. Misdiagnosis of unipolar depression may occur when patients with depressive symptomatology report no manic or hypomanic episodes. Furthermore, bipolar disease may begin as depression and develop into bipolar disorder. Primary care physicians can watch for several red flags in patients with depressive episodes, such as poor functioning in social and work arenas, risky behaviors, and legal issues. Other warning signs include a family history of bipolar disorder, psychosis at the index depressive episode, young age at onset of depression, and either antidepressant resistance or antidepressant-induced mania or hypomania. Correct and timely recognition of bipolar disorder by primary care physicians can provide long-lasting benefits for the patient.

CVS to phase out tobacco sales, launch smoking cessation program

Calling the decision "simply the right thing to do for the good of our customers and our company," CVS Caremark will stop selling all tobacco products at its more than 7,600 CVS/pharmacy locations by October 1. The February 5 announcement came a week after the U.S. Surgeon General issued renewed warnings about tobacco use on the 50th anniversary of the Surgeon General's landmark report linking smoking and poor health.

Improving the Early Recognition and Diagnosis of Bipolar Disorder

Article AbstractMisdiagnosis of bipolar disorder is widespread, in part because of the overwhelming presence of depressive symptoms. In general, patients tend to seek help during a depressive episode rather than a manic one, leading clinicians to inaccurately provide a unipolar diagnosis rather than one of bipolar depression. To aid in making a bipolar diagnosis, clinicians can watch for several red flags in patients with depressive episodes, such as earlier age at onset, family history of bipolar disorder, and the presence of psychotic features. Other tools to identify bipolar disorder include the updated DSM-5 as well as evidence on the relationship between bipolar disorder and metabolic syndrome. A correct and timely diagnosis of bipolar disorder is crucial for the well-being and proper treatment of the patient.See the entire activity.

Disruptive Mood Dysregulation Disorder and Chronic Irritability in Youth at Familial Risk for Bipolar Disorder

Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in the DSM-5. Youth with a family history of bipolar disorder (BD) are at increased risk for BD and non-bipolar psychopathology. No studies to date have examined rates of DMDD among offspring of parents with BD. This study examines the risk for DMDD in offspring of parents with BD compared to community controls and considers rates of chronic irritability (independent of a DMDD diagnosis) across diagnoses in youth with parents with BD. Modified DMDD criteria were applied post hoc to 375 offspring of parents with BD and 241 offspring, aged 6 to 17 years, of community control parents. We calculated odds ratios using generalized linear mixed models.Inaddition, we explored associations with a severe chronic irritability phenotype andvariousdiagnoses in the high-risk cohort. Offspring of parents with BD were more likely to meet criteria for DMDD than were the offspring of community control parents (Odds ratio [OR]= 8.3, 6.7% vs. 0.8%), even when controlling for demographic variables and comorbid parental diagnoses (OR= 5.4). They also had higher rates of chronic irritability compared to community controls (12.5% vs. 2.5%, χ(2)= 18.8, p< .005). Within the offspring of parents withBD, the chronic irritability phenotype was frequently present in offspring with diagnosesofBD,depression, attention-deficit/hyperactivity disorder, and disruptive behavior disorders. Like other non-BD diagnoses, family history of BD increases the risk for DMDD. Severe chronic irritability and temper tantrums are the core features of DMDD, and are associated with mood and behavioral disorders in youth at risk for BD.

Adjustment Difficulties and Caregiving Burdens Faced by College Students with a Parent with Bipolar or Depressive Disorders

College campuses often host students who come from families where one or more parent has been affected by a bipolar or depressive disorder. The present study sought to determine whether these students face unique challenges in college, including increased adjustment difficulties as well as greater caregiving burden associated with their parents’ illness. Participants (N = 89) were undergraduate students at a large public university in the South (27 had a parent with bipolar disorder; 30 had a parent with major depressive disorder [MDD]; 32 had no parent history of a mood disorder). Semistructured interviews were used to assess student symptoms of mood disorders and mood disorder symptoms within their immediate family. Self-report measures were used to assess college adjustment and levels of caregiving burden faced by the students. We found that students with a family history of bipolar disorder and MDD had significantly greater difficulty adjusting to college. These difficulties persisted even after controlling for whether the student themselves had been affected by a mood disorder. The students of a parent with either bipolar disorder or MDD also reported significantly more burden associated with caring for their parents. College campus mental health professionals need to be aware that students with a parent with bipolar disorder or MDD face unique challenges adjusting to college that are only partially related to an increased risk for mood disorders.

Clinical Lycanthropy: Delusional Misidentification of the “Self”

Clinical Lycanthropy: Delusional Misidentification of the “Self”

Evaluating differential developmental trajectories to adolescent-onset mood and psychotic disorders

BackgroundIt is an open question as to whether differential developmental trajectories, potentially representing underlying pathophysiological processes, can form the basis of a more useful typology in young persons who present for mental health care.MethodsA cohort of 605 young people was recruited from youth mental health services that target the early phases of anxiety, mood or psychotic disorders. Participants were assigned to one of three clinical sub-types (anxious-depression; mania-fatigue; developmental-psychotic) according to putative developmental trajectories.ResultsThe distribution of subtypes was: 51% anxiety-depression, 25% mania-fatigue and 24% developmental-psychotic, with key differences in demographic, clinical, family history and neuropsychological characteristics. When analyses were limited to 286 cases with ‘attenuated’ or sub-threshold syndromes, the pattern of differences was similar. Multinomial logistic regression demonstrated that compared to the developmental-psychotic subtype, both the mania-fatigue and anxiety-depression subtypes were younger and more depressed at presentation, but less functionally impaired. Other discriminating variables between the developmental-psychotic and mania-fatigue sub-types were that the latter were significantly more likely to have a family history of bipolar disorder but have less likelihood of impaired verbal learning; whilst the anxious-depression group were more anxious, more likely to have a family history of depression, and had a higher premorbid IQ level.ConclusionsThis cross-sectional evaluation provides preliminary support for differing developmental trajectories in young persons presenting for mental health care. Prospective follow-up is needed to examine the predictive validity of this approach and its relationships to underlying pathophysiological mechanisms.

Treatment Challenges of Atypical Depression: A Case Report

Symptoms such as mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity are classified as atypical features of a major depressive episode. If these symptoms are concurrent with an episode of hypomania, the patient would be diagnosed with having a depressive episode in the continuum of bipolar II disorder. Because patients may have subsequent depressive episodes for years without any symptoms of hypomania, and because they can function unequivocally within the community due to the nature of the disorder, the diagnosis of a bipolar disorder often gets misclassified as one of a unipolar etiol ogy. Most evidence-based literature states the complexity of this diagnosis due to the subtlety of the presenting symptoms, and it is usually only with a thorough patient history that a clinician can diagnose a patient with bipolar II disorder when the chief complaint is atypical depression. An integrative approach to classifying the depression in terms of polarity requires the clinician to consider the longitudinal course of the patient’s illness; the tendency for depression to recur; the onset, prominence, and severity of depressive episodes; and whether there is a family history of bipolar disorder. It is essential to distinguish between unipolar and bipolar depression in order to treat current episodes and prevent further depressive episodes. The firstline treatment for unipolar depression with atypical features is monoamine oxidase inhibitors (MAOIs), whereas first-line treatment for bipolar depres sion is a mood stabilizer that may be augmented with an antidepressant. CASE

Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution

BackgroundHighly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of ‘soft bipolarity’. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. MethodsOur primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. ResultsEpisodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10−7), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10−6 after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LimitationsEpisode count was self-reported and, therefore, subject to recall bias. ConclusionsOur findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a ‘soft bipolar spectrum’ but await replication in larger cohorts.

A prospective study of diagnostic conversion of major depressive disorder to bipolar disorder in pregnancy and postpartum

The aim of the present study was to determine the rate of, and risk factors for, a change in diagnosis from major depressive disorder to bipolar disorder, and from bipolar II disorder to bipolar I disorder in pregnancy and postpartum. Patients with a prior history of major depressive disorder or bipolar II disorder were recruited between 24 and 28 weeks' gestation and followed through to one year postpartum. Diagnostic interviews were conducted using the Structured Clinical Interview for DSM-IV at study intake and repeated using the Mini-International Psychiatric Interview at one, three, six, and 12 months after childbirth. Fisher's exact test was used to assess the association between various risk factors and diagnostic switch. A total of 146 participants completed the intake interview and at least one follow-up interview postpartum. Of these, 92 were diagnosed with major depressive disorder and 54 with bipolar II disorder at intake. Six women (6.52%) experienced a diagnostic change from major depressive disorder to bipolar II disorder during the first six months after childbirth. There were no cases of switching to bipolar I disorder, but in one participant the diagnosis changed from bipolar II disorder to bipolar I disorder during the three months after childbirth. Bipolar switch was associated with a family history of bipolar disorder. The postpartum period appears to be a time of high risk for a new onset of hypomania in women with major depressive disorder. Our rate of diagnostic switching to bipolar II disorder (6.52%) is at least 11- to 18-fold higher than the rates of switching in similar studies conducted in both men and women.

Memantine in the management of affective recurrences of bipolar disorders after the discontinuation of long-term lithium treatment: three case histories

Discontinuation of long-term lithium treatment leads to early and severe affective recurrences [Baldessarini et al. 1999], and to a bipolar disorder course more severe than that before lithium treatment with an increased risk of suicide [Post, 2012], which is often resistant not only to other mood stabilizers, but also to the reinstitution of lithium treatment at the prior effective serum lithium level [Post, 2012]. Unfortunately, the currently available lithium-alternative mood stabilizers are of limited (anticonvulsants) [Geddes et al. 2010; Kessing et al. 2011; Greil and Kleindiest, 1999], or questionable (atypical neuroleptics) [Goodwin et al. 2011] efficacy. We have recently provided clinical observations strongly suggesting that memantine, a noncompetitive N-methyl D-aspartate receptor antagonist, has a clinically relevant antimanic and a sustained mood-stabilizing effect in treatment-resistant bipolar disorder with excellent safety and tolerability [Koukopoulos et al. 2010, 2012; Sani et al. 2012; Serra et al. 2013]. More recently we have observed a long-lasting mood-stabilizing effect of memantine after lithium discontinuation in a bipolar I patient [Serra et al. 2013]. In order to evaluate further the effect of memantine in the prophylaxis of affective recurrences occurring after long-term lithium discontinuation, we administered the drug to three patients who had to discontinue lithium because of severe renal complications (two patients) or excessive tremor (one patient). These case histories confirm our previous observations, and suggest that memantine may be considered a useful lithium substitute to prevent the affective recurrences after lithium discontinuation. Case 1 Woman born in 1930, suffering from a bipolar II disorder with rapid cycling course. She has a family history of bipolar disorder. Her first affective episode was a depression in May 1979 (aged 49 years), followed by a hypomania until January 1980. She started lithium prophylaxis and had a very good response to lithium. In June 2009 lithium was gradually reduced to 150 mg every 2 days (serum lithium level 0.2 mmol/L) and then withdrawn because of renal impairment. After we had obtained the informed written consent, she was put on 20 mg/day memantine and lamotrigine (250 mg/day). She started with rapid cycling recurrences until May 2010. Since then she has been well and stable on memantine 20 mg/day, lamotrigine 250 mg/day and lithium 150 mg every 2 days (lithium serum level 0.2 mmol/L).

Major Depressive Disorder: Long-Term Course, Treatment, and Complications

Major Depressive Disorder: Long-Term Course, Treatment, and Complications

Bipolar II disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation

The neurobiological substrate of bipolar II disorder (BD-II) remains largely unknown. A few previous studies have found evidence for cerebral cortical thinning in mixed samples of BD-II and bipolar I disorder patients; however, no study of cortical thickness or surface area has been limited to BD-II. In the present study, we compared magnetic resonance imaging (MRI)-based indices of cortical thickness and surface area between individuals with BD-II and healthy controls. Thirty-six individuals with a DSM-IV diagnosis of BD-II and 42 controls underwent 3T MRI. Comparisons of thickness and relative surface areal expansion across the cerebral cortical mantle were performed using Freesurfer. Individuals with BD-II showed significant thinning in two prefrontal clusters primarily comprising the left subgenual anterior cingulate cortex, left perigenual ventromedial prefrontal cortex (PFC), bilateral dorsomedial PFC, and bilateral dorsolateral PFC (p < 0.0002 for both clusters, cluster size corrected) and in a left temporal cluster involving the superior, middle, and inferior temporal gyrus (p = 0.006, cluster size corrected). No group differences in cortical surface area were found. No significant effect of medication, mood state, illness duration, or family history of bipolar disorders on cortical thinning was observed. These results indicate that BD-II is associated with thinning of prefrontal and temporal cortices implicated in the expression and regulation of negative and positive affect. Longitudinal studies are needed to clarify whether cortical thinning is a stable trait of BD-II, an illness effect that might progress during the course of the disease, or a combination of the two.

A Case of Amelioration of Venlafaxine-Discontinuation “Brain Shivers” With Atomoxetine

To the Editor: Antidepressant discontinuation syndrome is a common syndrome seen following abrupt termination of treatment with a serotonin reuptake inhibitor.1 It occurs at rates ranging from 17.2% to as high as 78% with venlafaxine.2,3 There is, however, little literature on “brain shivers,”4,5 a common antidepressant-discontinuation symptom described by patients taking venlafaxine, duloxetine, citalopram, and paroxetine. Much of the information comes from Internet blogs and Web sites.6–8 The symptom is described variously as “an electrical shock–like sensation in the brain,” “the sensation of the brain shivering,” “brain zaps,” “brain shocks,” “brain shivers,” “head shocks,” or “cranial zings.” The etiology of the symptom is not known, and there is no known treatment for this distressing symptom. We describe a case in which “brain shivers” occurred as part of venlafaxine discontinuation syndrome and abated with atomoxetine treatment. Case report. Mr A, a 34-year-old man, presented with DSM-IV major depressive disorder (MDD) that responded well to venlafaxine (300 mg/d). He achieved remission except for seasonal exacerbations during autumn during the next 4 years. In view of a family history of bipolar disorder, it was decided to add lamotrigine and taper venlafaxine. Mr A maintained remission on venlafaxine (37.5 mg/d) and lamotrigine (200 mg/d) without seasonal exacerbations. Mr A abruptly discontinued venlafaxine 37.5 mg/d. On the second day following discontinuation, he reported feeling an unpleasant sensation of “electricity in the head” that “felt like the brain was shaking inside the skull.” Mr A was also noticed to demonstrate emotional incontinence and complained of anhedonia, anxiety, tinnitus, headache, nausea, and increased sensitivity to noise. Since the “brain shivers” were the most distressing symptom, a trial of atomoxetine 40 mg/d was attempted based on the hypothesis that the symptom was a result of noradrenergic imbalance.9 An immediate improvement in “brain shivers” was reported within 2 or 3 hours of taking the first dose. Over the next 3 days, Mr A reported further improvement in “brain shivers” and anhedonia although emotional incontinence and increased sensitivity to noise persisted. Given the severity of other withdrawal symptoms, venlafaxine (37.5 mg/d) was reinstated and atomoxetine was stopped. All withdrawal symptoms disappeared during the next day. The case adds to the interesting speculation about the noradrenergic imbalance as the basis of “brain shivers.”9 “Brain shivers,” conceptually related to Lhermitte’s phenomenon,10 have also been reported with the noradrenergic drug 3,4-methylenedioxy-N-methylamphetamine (MDMA). The psychotropic effects of MDMA are mediated via norepinephrine transporter11 and results in an increase in synaptic norepinephrine levels. Venlafaxine’s affinity for norepinephrine transporter (K[i] = 2,984 nM),12 is 103-fold lower than that of atomoxetine (K[i] = 5 nM),13 yet venlafaxine causes an increase (242%)14 in synaptic norepinephrine levels comparable to that by atomoxetine (290% ± 33%).13 Curiously, chronic treatment with venlafaxine does not reduce norepinephrine transporter binding sites.15 These facts point to the possibility that increases in synaptic norepinephrine are due to norepinephrine transporter reversal, akin to dopamine transporter reversal associated with amphetamine.16 Abrupt withdrawal of venlafaxine would hence result in paradoxical increase in synaptic norepinephrine via efflux through norepinephrine transporter channels, which is normalized by atomoxetine’s norepinephrine transporter blockade. This speculation of the noradrenergic basis of “brain shivers” warrants further study.

Risk factors for secondary substance use disorders in people with childhood and adolescent-onset bipolar disorder: Opportunities for prevention

BackgroundCompared to other mental illnesses, bipolar disorder is associated with a disproportionately high rate of substance use disorders (SUDs), and the co-occurrence is associated with significant morbidity and mortality. Early diagnosis of primary bipolar disorder may provide opportunities for SUD prevention, but little is known about the risk factors for secondary SUD among individuals with bipolar disorder. The purposes of this study were to describe the population of people with childhood and adolescent-onset primary bipolar disorder, and to identify risk factors for secondary SUD in this population. MethodsUsing data collected from the National Comorbidity Survey Replication study, we identified 158 individuals with childhood-onset (<13years) or adolescent-onset (13–18years) primary bipolar disorder (I, II or subthreshold). Survival analysis was used to identify risk factors for SUD. ResultsCompared to adolescent-onset, people with childhood-onset bipolar disorder had increased likelihoods of attention deficit hyperactivity disorder (ADHD) (adjusted odds ratio=2.81) and suicide attempt (aOR=3.61). Males were more likely than females to develop SUD, and did so at a faster rate. Hazard ratios of risk factors for SUD were: lifetime oppositional defiant disorder (2.048), any lifetime anxiety disorder (3.077), adolescent-onset bipolar disorder (1.653), and suicide attempt (15.424). SUD was not predicted by bipolar disorder type, family history of bipolar disorder, hospitalization for a mood episode, ADHD or conduct disorder. ConclusionsAs clinicians struggle to help individuals with bipolar disorder, this study provides information that might be useful in identifying individuals at higher risk for SUD. Future research can examine whether targeting these risk factors may help prevent secondary SUD.

Identifying antecedent and illness course variables differentiating bipolar I, bipolar II and unipolar disorders

BackgroundClinical differentiation of bipolar conditions (and especially bipolar II disorder) from unipolar conditions is not always straightforward. We sought to identify illness antecedents and correlates that may assist their differentiation and complement clinical symptoms. MethodsWe undertook detailed comparative analyses of comprehensive data obtained from patients diagnosed with a bipolar or unipolar mood disorder. ResultsThe sample comprised 138 bipolar (45 bipolar I and 93 bipolar II) and 214 unipolar participants. Univariate analyses identified numerous differentiating variables, while multivariate analyses generated a refined variable list to determine discriminatory capacity. Controlling for all other factors, those with a bipolar (I or II) condition were more likely than the unipolar sub-set to report a family history of bipolar disorder, experiencing bullying at school, to make a suicide/self-harm attempt, and be less likely to be clinically judged as having ‘problematic’ personality traits. Factors differentiating bipolar II from unipolar sub-sets included the aforementioned variables, as well as higher rates of lifetime heavy drinking and female gender, and briefer depressive episodes in the bipolar II group. Bipolar I and II sub-sets differentiated solely by higher rates of hospitalization in the former group. LimitationsSome study variables (e.g., hospitalization) may merely reflect DSM-IV diagnostic criteria or consequences rather than illness antecedents or correlates. Other self-reported variables (e.g., bullying) are subject to memory biases, and may reflect higher-order variables (e.g., early problematic personality traits). ConclusionsStudy findings provide assistance to determining non-symptom features that may improve discrimination of the bipolar disorders from themselves and from unipolar conditions.

Reduced Inferior Frontal Gyrus Activation During Response Inhibition to Emotional Stimuli in Youth at High Risk of Bipolar Disorder

Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.

A comprehensive analysis of features that suggest bipolarity in patients with a major depressive episode: Which is the best combination to predict soft bipolarity diagnosis?

BackgroundThe study aimed to identify specific predictors of soft bipolarity (bipolar II disorder or bipolar disorder not otherwise specified) in depressed patients and to evaluate the global predictive performance of combinations of these predictors. MethodsSubjects included 199 patients with a major depressive episode (MDE) due to soft bipolarity or major depressive disorder. Independent predictors of soft bipolar diagnosis were extracted from 12 previously proposed bipolar features using multiple logistic regression analyses, and the global performance of the combination of these predictors was evaluated using a receiver operating characteristic (ROC) curve. ResultsRecurrent MDEs, family history of bipolar disorders in first-degree relatives, cyclothymic temperament, early age at onset of first MDE, and depressive mixed state were independent predictors of soft bipolarity diagnosis [odds ratio (95% confidence interval): 11.22 (2.19–57.63), 8.82 (1.31–59.15), 7.32 (2.22–24.19), 6.22 (1.58–24.57), and 5.57 (1.91–16.30), respectively]. The area under the ROC curve for the relationship between soft bipolarity diagnosis and the number of these five predictors in each patient was 0.911 (highly accurate). The presence of one or more predictors in each patient resulted in highest sensitivity (92.5%) and good specificity (73.1%), whereas that of two or more predictors resulted in good sensitivity (70.0%) and highest specificity (97.5%) for soft bipolarity diagnosis. LimitationsStructured/semistructured interviews were not used. Tools for temperament assessments were different between institutions. ConclusionsA combination of these predictors was quite helpful for a precise diagnosis of soft bipolarity in patients with depression.