Bipolar NOS Research Articles

Differential Patterns of Abnormal Activity and Connectivity in the Amygdala–Prefrontal Circuitry in Bipolar-I and Bipolar-NOS Youth

The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Participants (18 BP-I youth, 16 BP-NOS youth, and 18 HC) underwent functional magnetic resonance imaging while performing two emotional-face gender labeling tasks (happy/neutral, fearful/neutral). Analyses focused on a priori neural regions supporting emotion processing (amygdala) and emotion regulation (ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC). Connectivity analyses used VMPFC as a seed region. During the happy-face task, BP-I youth had greater amygdala, VMPFC, and DLPFC activity to happy faces whereas BP-NOS youth had reduced VMPFC and DLPFC activity to neutral faces relative to HC, and reduced amygdala, VMPFC, and DLPFC activity to neutral faces versus BP-I. During the fearful-face task, BP-I youth had reduced DLPFC activity to fearful faces whereas BP-NOS youth had reduced DLPFC activity to neutral faces relative to HC. BP-NOS youth showed greater VMPFC-DLPFC connectivity to happy faces relative to HC and BP-I youth. BP-I youth showed reduced VMPFC-amygdala connectivity to fearful faces relative to HC and BP-NOS youth. This is the first study to document differential patterns of abnormal neural activity in, and connectivity between, neural regions supporting emotion processing and regulation in BP-NOS versus BP-I youth. Findings suggest that despite similarities in symptom presentation, there are differential patterns of abnormal neural functioning in BP-NOS and BP-I relative to HC, which might reflect an "intermediate state" in the course of BP-I illness. Future longitudinal studies are needed to relate these findings with future conversion to BP-I/II.

Progression along the bipolar spectrum: a longitudinal study of predictors of conversion from bipolar spectrum conditions to bipolar I and II disorders

Little longitudinal research has examined progression to more severe bipolar disorders in individuals with soft bipolar spectrum conditions. We examine rates and predictors of progression to bipolar I and II diagnoses in a nonpatient sample of college-age participants (n = 201) with high General Behavior Inventory scores and childhood or adolescent onset of soft bipolar spectrum disorders followed longitudinally for 4.5 years from the Longitudinal Investigation of Bipolar Spectrum (LIBS) project. Of 57 individuals with initial cyclothymia or bipolar disorder not otherwise specified (BiNOS) diagnoses, 42.1% progressed to a bipolar II diagnosis and 10.5% progressed to a bipolar I diagnosis. Of 144 individuals with initial bipolar II diagnoses, 17.4% progressed to a bipolar I diagnosis. Consistent with hypotheses derived from the clinical literature and the Behavioral Approach System (BAS) model of bipolar disorder, and controlling for relevant variables (length of follow-up, initial depressive and hypomanic symptoms, treatment-seeking, and family history), high BAS sensitivity (especially BAS Fun Seeking) predicted a greater likelihood of progression to bipolar II disorder, whereas early age of onset and high impulsivity predicted a greater likelihood of progression to bipolar I (high BAS sensitivity and Fun-Seeking also predicted progression to bipolar I when family history was not controlled). The interaction of high BAS and high Behavioral Inhibition System (BIS) sensitivities also predicted greater likelihood of progression to bipolar I. We discuss implications of the findings for the bipolar spectrum concept, the BAS model of bipolar disorder, and early intervention efforts.

Stutter Exacerbated by Lithium in a Pediatric Patient with Bipolar Disorder

To report the first known case of a lithium-exacerbated stutter in a pediatric patient. A 10-year-old male with a history of developmental stuttering, bipolar disorder not otherwise specified (NOS), attention-deficit/hyperactivity disorder, and conduct disorder was admitted to the psychiatric hospital because of recurrent suicidal ideations and increased physical aggression toward staff at his residential facility. The patient was being treated with lithium at initial dose of 150 mg/day at bedtime for bipolar disorder NOS. When the lithium dose was increased to 900 mg twice daily to better control the bipolar symptoms, his developmental stutter worsened intensely. When the lithium dose was reduced to 600 mg in the morning and 900 mg at night, the stutter returned to baseline. No other medication changes were made during this interval. His serum lithium concentration was 0.62 mEq/L at baseline, 1.24 mEq/L during the height of his exacerbated stutter, and returned to 0.64 mEq/L after dose reduction. To our knowledge, only 1 case of lithium-exacerbated stutter has been reported in the literature, and this was in an adult. The developmental stutter of our pediatric patient worsened when he was treated with higher doses of lithium. He was on stable doses of his other medications during the adjustments to the lithium dose, making it less likely that the stutter was due to one of these medications. However, it is possible that the exacerbation involved an interaction between lithium and one or several of the other medications. Based on the Naranjo probability scale, this case represents a probable adverse drug reaction. Clinicians should be aware that an additional adverse effect of lithium may be an exacerbation of stutter.

Course of Subthreshold Bipolar Disorder in Youth: Diagnostic Progression From Bipolar Disorder Not Otherwise Specified

To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.

Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?

The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.

Bipolar disorder co-morbidity in children with attention deficit hyperactivity disorder

The present study aimed at: (1) exploring rate and clinical features of superimposed bipolar disorder (BD) in Italian children with attention deficit hyperactivity disorder (ADHD), compared with a community sample, matched for age and gender; (2) exploring predictors of BD in ADHD children, by comparing ADHD children with or without superimposed BD. We studied 173 consecutive drug-naïve outpatients with ADHD (156 males and 17 females, mean age of 9.2±2.3years, age range 6–17.5years), diagnosed with a clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)); the control group consisted of a community-based sample of 100 healthy children. The rate of children with a diagnosis of BD was higher in the ADHD group (29/173, 16.7%) compared with controls (1/100, 1%), (P<0.001). Among the 29 children with ADHD+BD, 16 (55.2%) had a Bipolar Disorder-Not Otherwise Specified (BD-NOS), and 11 (37.9%) showed ultrarapid cycling. Compared with children with ADHD without BD, they showed a higher rate of combined sub-type (21/29, 72.4%), a higher score at ADHD-Rating Scale (total score and hyperactivity subscale), higher rates of major depression, oppositional defiant disorder and conduct disorder. In summary, children with ADHD present a higher risk for developing a superimposed BD. The identification of clinical features with an increased risk of BD can improve diagnosis, prognosis and treatments.

Late-life bipolar depression due to the soft form of bipolar disorder compared to unipolar depression: An inpatient chart review study

BackgroundSeveral studies have been conducted regarding the clinical features of the manic state in elderly patients with bipolar disorder; however, little information is available about bipolar depression in these patients, especially depression related to bipolar II disorder (BP-II) and bipolar disorder not otherwise specified (BP-NOS). MethodsA chart review study of 87 patients (age≥60 years) hospitalized due to a major depressive episode (MDE) was conducted. ResultsThirty-two (36.8%) and 55 (63.2%) patients were diagnosed with bipolar disorder and major depressive disorder (MDD), respectively. BP-II/BP-NOS accounted for 81.3% of bipolar disorder and 29.9% of MDE. Of the 26 BP-II/BP-NOS patients, 73% had been initially diagnosed with MDD (61.0%) or others (12.0%). Compared to MDD patients, BP-II/BP-NOS patients showed a significantly younger age-at-onset of the first MDE (median, 52 vs. 66 years, p=0.000) and significantly more frequent MDEs (median, 3 vs. 1, p=0.000). The depressed mixed state (DMX) was observed in 61.5% of BP-II/BP-NOS patients in contrast to only 16.4% of MDD patients (p=0.000). The multiple logistic regression analysis revealed that younger age at onset of first MDE and DMX were independent markers of bipolarity. LimitationsCertain features were retrospectively specified by a single reviewer. ConclusionLate-life depression due to BP-II/BP-NOS is generally misdiagnosed, but should never be neglected in elderly inpatients. Some features of the depression suggest bipolarity. In particular, DMX was found to be an independent marker of bipolarity, which supports the mixed nature of this disorder across generations.

Multinutrient Supplement as Treatment: Literature Review and Case Report of a 12-Year-Old Boy with Bipolar Disorder

Early-onset bipolar disorder has significant morbidity and mortality. Development of safe, effective treatments to which patients will adhere is critical. Pharmacologic interventions for childhood bipolar spectrum disorders are limited and are associated with significant risk for adverse events. Diet and nutrition research suggests vitamins, minerals, and other nutrients are important underpinnings of general physical and mental health; furthermore, they may even be useful in treating mood dysregulation by providing a more favorable risk-benefit ratio than contemporary psychotropic agents. This article reviews the literature on multinutrient supplementation and mental health, and examines a case study of a 12-year-old boy with bipolar disorder and co-morbid diagnoses treated for 6 years with conventional medication and finally a multinutrient supplement. The multinutrient supplement in this case study is EMPowerplus (EMP+), a 36-ingredient supplement containing 16 minerals, 14 vitamins, 3 amino acids, and 3 antioxidants. It was used to treat a 12-year-old boy initially diagnosed with bipolar disorder not otherwise specified (BP-NOS) at age 6, and whose diagnosis evolved by age 10 to bipolar I (BP-I), mixed, with psychotic features. He also met criteria for generalized anxiety disorder by age 8 and obsessive-compulsive disorder by age 10. After 6 years of conventional treatment (ages 6-12), he received 14 months of EMP+. Symptom manifestation over 7 years is described in conjunction with treatment history. EMP+ resulted in outcome superior to conventional treatment. This report adds to accumulating preliminary evidence that further basic science and clinical studies of multinutrient supplements are warranted.

Low-dose quetiapine for patients with dysregulation of hyperthymic and cyclothymic temperaments

Patients with hyperthymic and cyclothymic temperaments often develop symptoms that fail to meet diagnostic criteria for bipolar disorders. These patients can be conceived as having bipolar disorder NOS (not otherwise specified), a bipolar spectrum disorder, cyclothymic disorder or cluster B personality traits. Here, we describe four of these patients with mild to moderate symptoms affecting mood, behaviour, emotional reactivity and sleep. Treatment with low-dose quetiapine (25-75 mg/day at night) lead to sustained symptom remission. Two of them were on quetiapine monotherapy. Such low doses occupy a minority of D2 and 5-HT2 receptors, which may nevertheless be of therapeutic value in mild cases. Alternatively, other mechanisms more likely to occur at low doses, such as antagonism of H1, alpha(1B)-adrenergic and other serotonin receptors, as well as reduction cortisol secretion, may be involved in the therapeutic efficacy of quetiapine.

Quetiapine in post-transplant acute mania/bipolar disorder NOS

There is no medication specifically approved for the treatment of bipolar disorder not otherwise specified (BD-NOS), substance-induced mood disorders and mood disorders due to a general medical condition. We report the case of a man whose post-transplant BD-NOS was treated successfully with quetiapine. Mr G, a 58-year-old man with cystic fibrosis and no history of psychiatric disorders, as documented by a pre-transplant SCID evaluation, received lung transplantation in December 2004. The patient underwent the post-transplant course with no medical or psychiatric complications until 6 wk after the transplant, when he developed decreased need for sleep, euphoria, irritability, grandiosity, pressured speech, flights of ideas, increased sexual drive, mystical and grandiose delusions. His symptoms led him to a poor adherence to the post-transplant immunosuppressant treatment and to other …

Bipolar Disorder not Otherwise Specified: Comparison with Bipolar Disorder I/II and Major Depression

To compare the personality, clinical and comorbidity characteristics of subjects meeting diagnostic criteria for bipolar disorder not otherwise specified (BDNOS) to those with major depression and bipolar I or II disorder. A family-based study was undertaken on the molecular genetics of depression and personality, in which the proband had been treated for depression, regardless of history, of hypomania or mania. The 25 subjects with BDNOS were different to the 297 subjects with major depression and similar to 75 subjects with bipolar I or II disorder on social phobia, obsessive-compulsive disorder and substance dependence comorbidity. The BDNOS subjects also had personality traits more akin to the bipolar I or II disorder subjects, especially borderline personality traits and self transcendence. Subjects with BDNOS, based on a history of 1-3 day recurrent hypomanias, should be included within a broader bipolar spectrum.

It May Be Time to Rethink Bipolar Classification in Youth

It May Be Time to Rethink Bipolar Classification in Youth

Phenomenology of Children and Adolescents With Bipolar Spectrum Disorders

Children and adolescents who present with manic symptoms frequently do not meet the full DSM-IV criteria for bipolar I disorder (BP-I). To assess the clinical presentation and family history of children and adolescents with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise specified (BP-NOS). Subjects and their primary caretaker were assessed by semistructured interview, and family psychiatric history was obtained from interview of the primary caretaker. Outpatient and inpatient units at 3 university centers. A total of 438 children and adolescents (mean +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n = 153). Lifetime psychiatric history and family history of psychiatric disorders. Youth with BP-NOS were not diagnosed as having BP-I primarily because they did not meet the DSM-IV duration criteria for a manic or mixed episode. There were no significant differences among the BP-I and BP-NOS groups in age of onset, duration of illness, lifetime rates of comorbid diagnoses, suicidal ideation and major depression, family history, and the types of manic symptoms that were present during the most serious lifetime episode. Compared with youth with BP-NOS, subjects with BP-I had more severe manic symptoms, greater overall functional impairment, and higher rates of hospitalization, psychosis, and suicide attempts. Elevated mood was present in 81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP-II had higher rates of comorbid anxiety disorders compared with the other 2 groups and had less functional impairment and lower rates of psychiatric hospitalization than the subjects with BP-I. Children and adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with that of youth with BP-I. Elevated mood is a common feature of youth with BP-spectrum illness.

Declarative memory impairment in pediatric bipolar disorder

Impaired verbal declarative memory has been proposed as a trait marker for adult bipolar disorder. However, similar impairments in juvenile-onset bipolar disorder have not been yet documented. Here, we assessed declarative memory in a large sample of clinically well-characterized children with bipolar disorder. Forty-one children and adolescents with bipolar disorder [21 bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar disorder, not otherwise specified (BP-NOS)] and 17 demographically matched healthy participants completed a standardized learning and memory test. BP-I children recalled and recognized significantly fewer words than healthy subjects, whereas children with BP-II and BP-NOS did not differ from controls. However, individuals with BP-NOS made more perseverative errors and intrusions than the other groups. Severity of mood symptomatology was not associated with memory performance in any bipolar subtype. Findings suggest that declarative memory impairments in juvenile BP-I are similar to those seen in the adult form of the illness. These impairments do not appear to be secondary to clinical state; rather, they may reflect trait-related impairments. Distinct performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined phenotype is significantly heterogeneous, and may not be informative for pathogenetic investigations of bipolar disorder.