Bipolar NOS Research Articles

Do prospective longitudinal studies of bipolar disorder support the hypothesis of neuroprogression?

IntroductionBipolar I disorder is a mental disorder with the risk of severe clinical outcomes. Bipolar disorder was initially defined based on having a better outcome than schizophrenia. However, while recent longer-term findings in schizophrenia do not support neuroprogression, bipolar disorder is increasingly depicted as having neuroprogressive elements. There are, however, remarkably few prospective longitudinal studies of representative bipolar I cohorts followed from the first treatment.ObjectivesTo study the clinical development of a representative cohort of bipolar disorder patients recruited at their first treatment.MethodsPatients with DSM-IV Bipolar I or Bipolar NOS were consecutively recruited from in-and outpatient units in the larger Oslo area during their first treatment year and extensively clinically characterized at baseline. They then participated in personal one- and ten-year follow-ups.ResultsSixty-nine patients participated in the 10-year follow-up. Age at follow-up was 39.0 (+ 9.6) years, 59% were females. A total of 12% had unipolar mania, 58% had psychotic bipolar disorder, and 20% had experienced rapid cycling. At follow-up, 75% were in full affective remission, 60% had regained full functioning, and 54% were in stable full recovery.Mood episode relapses clustered around the first episode. Despite occasional relapses, 2/3 were mainly euthymic during the follow-up period. A small sub-group was highly affected from the first 2-3 years of treatment, but there were no apparent signs of kindling effects or indications of neuroprogressionConclusionsThe follow-up of this cohort of first-treatment Bipolar I patients does not support the hypothesis of neuroprogression.Disclosure of InterestNone Declared

Premorbid characteristics of patients with DSM-IV psychotic disorders

IntroductionPsychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group. MethodsWe included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ). ResultsParticipants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F2, 1029 = 7.81, p < 0.001, pη2 = 0.015). Premorbid social adjustment was significantly worse in the SSD group compared to the PBD group (F2, 1024 = 3.10, p = 0.045, pη2 = 0.006), with PNOS in the middle position. Significantly more of the participants with PNOS (17.5%) and SSD (11.5%) used cannabis before the age of 16 compared with PBD (5.3%, Wald χ2 = 6.86, p = 0.03). There were no significant differences between the three groups regarding mean CTQ scores or in the proportion of participants who had experienced at least one type of childhood adversity. ConclusionsParticipants with PNOS appear as more similar to participants with SSD than to those with PBD regarding early premorbid adjustment and early cannabis use. The results indicate that many conditions classified as PNOS have functional impairments and problematic substance use from an early age. The prevalence of childhood adversities are high in all three groups.

Evaluation of Clinical Parameters of Patients with Bipolar Disorder According to Gender and Family History

Background: Family history is one of the most important known risk factors for the occurrence of bipolar disorder (BD). Identifying clustering factors in BD families may facilitate the identification of the hereditary sub-phenotypes of the disorder and might reveal the underlying genetic features. This retrospective study aimed to investigate the effect of family history and gender on the clinical features of the disease in a large BD sample followed in a specialized mood center in Turkey. Methods: Research was carried out by reviewing the medical files of patients diagnosed with bipolar disorder who were followed up in the Rasit Tahsin Mood Clinic. Family histories and other demographic and clinical information of the patients were retrieved from the Mood Disorders Patient Registration Form (SKIP-TURK) completed for each patient. A patient’s family history was considered positive if any diagnosis of mood disorders and/or psychotic disorders was present in their first and/or second-degree relatives. Results: Family history was positive in 64.5% (n = 474) of 735 patients whose family history was recorded. Female patients made up 59.9% of the sample. Eighty point three percent (n = 590) of the patients were diagnosed with type 1 BD, 8.4% (n = 62) with type 2 BD, 11.3% (n = 83) with bipolar disorder not otherwise specified (BD-NOS). In the sample divided into 4 groups according to gender and family history, differences in the age at onset of the illness (F = 3.662, p = .012) were found to be statistically significant. In post hoc analysis, a significant difference was obtained between female patients without a positive family history and patients with a relevant family history. Regardless of family history status, the type of first episode in male patients tended to be hypomania/mania. Regarding treatment preferences, there was no significant difference between patients with and without a positive family history. Conclusions: In the literature, some studies evaluating the familial burden only included first-degree relatives, while others considered first- and second-degree relatives, and some studies defined the family history including only relatives with mood disorders, while others would include any psychiatric disease. In the present study, family history of those diagnosed with mood disorders and/or psychotic disorders in their first- and/or second-degree relatives was considered positive. This study provides valuable information by evaluating the effect of family history and gender on the clinical features of the disease in a large BD sample in Turkey.

Clinical features and patterns of psychopharmacological prescription in bipolar patients with vs without anxiety disorders at onset.

Up to just over half of bipolar disorder (BD) patients report at least one-lifetime anxiety disorder (AD). In some, anxiety represents the earliest psychiatric manifestation, prior to any mood episode. We sought to investigate prevalence of AD subtypes as first psychiatric manifestations and AD's relations with duration of untreated illness (DUI) and treatment among BD outpatients. We recruited patients referred to the Centre for the Treatment of Depressive Disorders in Milan, diagnosed with BD-I, BD-II, BD not otherwise specified (BD-NOS) and cyclothymia according to Diagnostic and Statistical Manual fourth edition-text revision criteria. Several clinical characteristics were assessed through retrospective chart review and/or direct patient interviews. Based on presence/absence of an AD at psychiatric onset, eligible subjects were stratified into two groups (A+ and A-) and clinical features were compared between these groups and between BD subtypes. We analysed 260 BD patients (77 BD-I, 122 BD-II, 45 BD-NOS and 16 cyclothymia). An AD was the first psychiatric manifestation in 69 patients (26.5%). BD-II and BD-NOS more frequently had an AD at psychiatric onset, with panic disorder being the most common AD. Among A+ vs A-, age at BD onset was younger, duration of untreated BD illness (DUI) was longer, and a mood stabilizer/antipsychotic was less often prescribed at psychiatric onset. Considering BD in its longitudinal course, over one in four BD patients presenting with an AD at psychiatric onset belatedly access adequate treatment, with subsequent prolonged DUI and prospective worse outcome compared to patients with a mood episode at psychiatric onset.

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder

BackgroundMost previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities.AimsTo study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance.MethodsA nationwide non-interventional study using psychiatrists’ and patients’ surveys.Results839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance.ConclusionIn contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.

A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths at Genetic High Risk for Bipolar Disorder.

To determine if acute treatment with aripiprazole (APZ) would be superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering from "cyclotaxia." This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17 years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive either APZ or placebo. Eligible participants had at least one parent with BPD, another first- or second-degree relative afflicted with a mood disorder, and also had not responded to psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1 mg/kg/day and could be increased by approximately 0.05 mg/kg/day at each study visit. Patients were seen weekly for 4 weeks and then every other week thereafter for 12 weeks. The primary outcome measure was mean change from baseline on Young Mania Rating Scale (YMRS) total score. A total of 59 patients (30 APZ, 29 placebo) aged 11.8 (SD = 2.7) years were randomized and returned for at least one postbaseline assessment. The mean total daily doses of active APZ and placebo were 7.1 mg (SD = 3.7) and 7.4 mg (SD = 4.2), respectively. At the 12-week time point, APZ was superior to placebo on the primary outcome measure (p < 0.005). Most adverse events were mild and transient in nature. There was a significant difference in weight gain from baseline between patients who received APZ (2.3 kg [SD = 3.3]) and those who received placebo (0.7 kg [SD = 1.8]). This double-blind trial found that APZ was significantly more efficacious than placebo in reducing symptoms of mania in children and adolescents with cyclotaxia.

A Case of Bipolar Affective Disorder Not Otherwise Specified Or Cyclothymia

The symptoms of mood disorders can be highly variable from person to person, and there are some differences in the present systems of classification to view some of the presentations of Bipolar Disorder Not Otherwise Specified (BPAD-NOS) and cyclothymia. This case highlights one of such presentations.Health Renaissance 2014;12(3): 221-223

Disruptive Mood Dysregulation Disorder and Bipolar Disorder Not Otherwise Specified: Fraternal or Identical Twins?

The purpose of this study was to examine similarities and differences between disruptive mood dysregulation disorder (DMDD) and bipolar disorder not otherwise specified (BP-NOS) in baseline sociodemographic and clinical characteristics and 36 month course of irritability in children 6-12.9 years of age. A total of 140 children with DMDD and 77 children with BP-NOS from the Longitudinal Assessment of Manic Symptoms cohort were assessed at baseline, then reassessed every 6 months for 36 months. Groups were similar on most sociodemographic and baseline clinical variables other than most unfiltered (i.e., interviewer-rated regardless of occurrence during a mood episode) Young Mania Rating Scale (YMRS) and parent-reported General Behavior Inventory-10 Item Mania (PGBI-10M) items. Children with DMDD received lower scores on every item (including irritability) except impaired insight; differences were significant except for sexual interest and disruptive-aggressive behavior. Children with DMDD received lower scores on eight of 10 PGBI-10M items, the other two items rated irritability. Youth with DMDD were significantly less likely to have a biological parent with a bipolar diagnosis than were youth with BP-NOS. Children with DMDD were more likely to be male and older than children with BP-NOS, both small effect sizes, but had nearly double the rate of disruptive behavior disorders (large effect). Caregiver ratings of irritability based on the Child and Adolescent Symptom Inventory-4R (CASI-4R) were comparable at baseline; the DMDD group had a small but significantly steeper decline in scores over 36 months relative to the BP-NOS group (b = -0.24, SE = 0.12, 95% CI -0.48 to -0.0004). Trajectories for both groups were fairly stable, in the midrange of possible scores. In a sample selected for elevated symptoms of mania, twice as many children were diagnosed with DMDD than with BP-NOS. Children with DMDD and BP-NOS are similar on most characteristics other than manic symptoms, per se, and parental history of bipolar disorder. Chronic irritability is common in both groups. Comprehensive evaluations are needed to diagnose appropriately. Clinicians should not assume that chronic irritability leads exclusively to a DMDD diagnosis.

Negative cognitive styles synergistically predict suicidal ideation in bipolar spectrum disorders: A 3-year prospective study

Rates of suicidal ideation and behavior are extremely high in bipolar spectrum disorders (BSDs). However, relatively little work has evaluated potentially synergistic relationships between cognitive and emotion-regulatory processes proposed by theoretical models of suicidality in BSDs. The present study evaluated whether negative cognitive style and subtypes of rumination would exacerbate the impact of self-criticism on suicidal ideation in a prospective study of individuals with BSDs. Seventy-two young adults with BSDs (bipolar II, bipolar NOS, or cyclothymia) completed diagnostic interviews and trait measures of self-criticism, negative cognitive style, and brooding and reflective rumination at a baseline assessment. The occurrence of suicidal ideation was assessed as part of diagnostic interviews completed every 4 months for an average of 3 years of follow-up. Negative cognitive style and reflective rumination strengthened the association between self-criticism and the prospective occurrence of suicidal ideation across follow-up. Individuals with high levels of self-criticism in conjunction with negative cognitive style or reflective rumination were most likely to experience the onset of suicidal ideation. Self-criticism may work synergistically with negative cognitive style and rumination to confer risk for suicidal ideation in bipolar spectrum disorders. These results support theoretical models of suicidality in BSDs and indicate that evaluating and understanding negative cognitive styles may help to identify individuals who are at risk of suicide.

Irritability as a criterion in diagnosis of child and adolescent bipolar disorder: thorny road ahead.

Byline: M. Reddy Diagnostic and Statistical Manual of Mental Disorders, 5 [sup]th edition (DSM 5) [sup][1] of bipolar disorder (BD) makes it necessary to meet the following criteria for a manic episode: distinct period of abnormally and persistently elevated, expansive, OR IRRITABLE MOOD… lasting at least one week and present most of the day, nearly everyday…. It is elation or irritation, along with three or four other symptoms. DSM 5 criteria for BD are applicable to all age groups with the same weightage. Irritable occupies a prominent place in the diagnostic criteria of many other disorders, especially childhood and adolescent disorders like oppositional defiant disorder; intermittent explosive disorder; conduct disorder; disruptive mood dysregulation disorder (DMDD); other and unspecified disruptive, impulse control, and conduct disorders; and attention deficit/hyperactivity disorder (ADHD) in the classificatory systems. With irritable sharing space in the diagnostic criteria of BD and several childhood and adolescent diagnostic disorders, there looms a possibility of over diagnosis of childhood adolescent bipolar disorder. misdiagnosis, whenever it occurs, hopefully less often, leads to a major therapeutic mismatch resulting in polypharmacy and treatment failures. National Institute of Mental Health research roundtable on prepubertal bipolar disorder, 2001 recommends that patients with grandiosity/elation be classified as bipolar I and irritability/rage be classified as bipolar NOS (DSM IV TR). There was always a doubt about reliability of irritability as a symptom criterion in the of mania as shown in this USA-UK study: USA-UK project (2005) Elation/grandiose - mania - 96.4% USA and 88.9% UK Irritability/rage - mania - 86.2% USA and 31.1% UK There is rather unacceptable poor concordance, with irritability as the criterion. A few valid arguments that merit attention are the following: *That delusions/hallucinations occur only in BD (true, but a significant majority of patients with BD do not have delusions/hallucinations). *Family H/O of BD favors of bipolar illness (yes, very valuable supporting point in those who have a family history). *BD is an episodic disorder, whereas other childhood disorders outlined above are all continuous in course. Is it true? Let us look at the existing data. Evidence Age of onset The greatest frequency of first attacks falls, however, in the period of development with its increased emotional excitability between the fifteenth and twentieth In rare cases, the first beginnings can be traced back even to before the tenth year…. - Kraepelin, 1921 In 28% of the BD patients recruited into the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, age at onset was younger than 13, and in the Bipolar Collaborative Network study, 15% of patients had illness onset before the age of 13 years. younger age of onset in BD seems to be a well-documented fact. Diagnosis Some studies have defined mania by the presence of highly labile moods with intense irritability, rage, explosiveness and destructiveness; extreme agitation, and behavioral dysregulation. [sup][2],[3],[4],[5] picture that emerges from several independent research groups is that prepubertal children with BD typically have multiple daily mood swings and that irritability is much more common than euphoria. [sup][6],[7] Course Studies indicate a highly pernicious course with substantial chronicity. In 81% of a well-defined group of patients, Geller et al . [sup][6] reported continuous daily cycling from mania or hypomania to euthymia or depression. In this study, 1-year mania recovery rate stood at 37%. …

Effects of Comorbid Anxiety Disorders on the Longitudinal Course of Pediatric Bipolar Disorders

To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP). As part of the Course and Outcome of Bipolar Youth study, 413 youth, who were 7 through 17 years or age and who met criteria for DSM-IV BP-I (n= 244), BP-II (n= 28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n= 141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed. At intake and during the follow-up, 62% of youth with BP met criteria for at least 1 anxiety disorder. About 50% of the BP youth with anxiety had≥2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with≥2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety. Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, and more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youthwith anxiety are warranted.

Comparison of clinical characteristics of bipolar and depressive disorders in Korean clinical sample of youth: a retrospective chart review

The purpose of this study was to compare the clinical characteristics of bipolar disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of major depressive disorder (MDD) in a clinical sample of Korean children and adolescents. This study was a cross-sectional review of longitudinal observational data. Two psychiatrists retrospectively reviewed the medical records of 198 children and adolescents (age 6-18) that were diagnosed as having bipolar or depressive disorders from March 2010 to February 2012 at Department of Psychiatry of Asan Medical Center, Seoul, Korea. Every subject's diagnoses were reviewed and confirmed. BD I, II and MDD were assessed according to the Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made in demographic information, clinical characteristics, family history, and psychiatric comorbidities at baseline and during observation. Among 198 subjects, 20 (10.1%) subjects were diagnosed as having BD I, 10 (5.1%) as BD II, 25 (12.6%) as BD NOS and 143 (73.7%) as MDD. BD depression was associated with mood change while taking an antidepressant, familial bipolarity, aggressive behaviors, and atypical features. Comorbid obsessive-compulsive disorder tended to be higher in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD than in BD depression. In children and adolescents, bipolar depression is distinct from unipolar depression in family history, comorbidity, and clinical characteristics.

Association between the so-called “activation syndrome” and bipolar II disorder, a related disorder, and bipolar suggestive features in outpatients with depression

BackgroundActivation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression. MethodsThe frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively. ResultsOf 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS. LimitationsThis is a retrospective and naturalistic study; therefore, patient selection bias could have occurred. ConclusionsCautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar–bipolar dichotomy. Prospective studies are needed to confirm these results.

Occupational outcome in bipolar disorder is not predicted by premorbid functioning and intelligence

Bipolar disorder (BD), over the long term, can manifest a variety of outcomes depending on a number of different conditions. There is a need for further knowledge regarding preventive factors as well as predictors of the disabling course of the disorder. Studies regarding the impact on functional outcome of premorbid and current general intellectual function [intelligence quotient (IQ)] and premorbid functioning in BD patients are sparse. The present study addressed the role of premorbid functioning [assessed with the Premorbid Adjustment Scale (PAS)], intelligence, course of illness, and sociodemographics on occupational outcome in BD. Bipolar disorder patients were recruited consecutively from psychiatric units (outpatient and inpatient) in four major hospitals in Oslo, Norway [(N = 226: 64.4% bipolar I disorder (BD-I); 30.1% bipolar II disorder (BD-II); 5.5% bipolar disorder not otherwise specified (BD-NOS); 38.6% males]. The associations between current IQ, premorbid IQ [assessed using the National Adult Reading Test (NART)], PAS, clinical and sociodemographic characteristics, and receipt of disability benefit were analysed using descriptive statistics and logistic regression analyses. The number of hospitalizations for depressive episodes and illness duration was associated with a higher risk of receipt of disability benefit. PAS, premorbid and current IQ, as well as decline in IQ, did not explain the higher risk of receipt of disability benefits. Severe clinical course of BD was associated with receipt of disability benefit. Occupational outcome was unrelated to PAS, premorbid and current IQ, as well as decline in IQ. This suggests that the persistence of severe clinical symptoms, rather than global cognitive functioning, determines occupational outcome in BD and emphasizes the protective potential of early and continuous clinical treatment.

Phenomenology of bipolar disorder not otherwise specified in youth: a comparison of clinical characteristics across the spectrum of manic symptoms

Controversy surrounds the diagnostic categorization of children with episodic moods that cause impairment, but do not meet DSM-IV criteria for bipolar I (BD-I) or bipolar II (BD-II) disorder. This study aimed to characterize the degree to which these children, who meet criteria for bipolar disorder not otherwise specified (BD-NOS), are similar to those with full syndromal BD, versus those with no bipolar spectrum diagnosis (no BSD). Children aged 6-12 years were recruited from nine outpatient clinics, preferentially selected for higher scores on a 10-item screen for manic symptoms. Interviews with the children and their primary caregivers assessed a wide array of clinical variables, as well as family history. A total of 707 children [mean ± standard deviation (SD) 9.4 ± 1.9 years old] were evaluated at baseline, and were diagnosed with BD-I (n = 71), BD-II (n = 3), BD-NOS (including cyclothymia; n = 88), or no BSD (n = 545). Compared to BD-I, the BD-NOS group had less severe past functional impairment. However, current symptom severity and functional impairment did not differ between BD-NOS and BD-I, even though both groups were significantly more symptomatic and impaired than the no BSD group. Parental psychiatric history was similar for the BD-NOS and BD-I groups, and both were more likely than the no BSD group to have a parent with a history of mania. Rates of elated mood did not differ between BD-NOS and BD-I youth. Children with BD-NOS and BD-I are quite similar, but different from the no BSD group, on many phenomenological measures. These findings support the hypothesis that BD-NOS is on the same spectrum as BD-I.

Onset of Abnormal Movements and Cardiovascular Symptoms after Acute Change in Complex Polypharmacy in a Child with Attention-Deficit/Hyperactivity Disorder and Mood Symptoms

T. was being treated in the community for diagnoses of attentiondeficit/hyperactivity disorder (ADHD) and bipolar disorder, not otherwise specified (BD-NOS). T.’s mother reported that T. had had many ADHD symptoms present since kindergarten, including difficulty with concentration and completion of tasks, inattention, restlessness, impulsivity, frequent interruption of conversations, and need for constant redirection. T. also was reported to have other behavioral problems, including refusal to follow directions and aggressive behavior toward family members, including slamming or punching objects. In the previous few months, he was reported to have become more oppositional and more disrespectful, and he had attempted to set fires and been cruel to animals. T.’s mother also reported that T. had experienced difficulty with emotional regulation, and had threatened to hurt himself in the past when angry. He also reportedly had had brief crying spells when he was upset. His mood was reported to be irritable when he did not have his desires fulfilled; T. himself reported his mood as ‘‘sad and mad’’ most of the time. His mother reported that he had experienced difficulty sleeping, typically going to bed at 1:30 a.m. and waking up at 6:30 a.m. T. was reported to have nightmares at times, but he was not able to recall the content. His mother denied that he had demonstrated grandiosity, elevated mood, racing thoughts, or pressured speech. There was no history of suicidal ideation, suicide attempts, or psychotic symptoms. There was no history of abuse, trauma, tics, obsessive compulsive and anxiety symptoms, or use of substances. T. had been treated for his aggressive behavior by an outpatient child and adolescent psychiatrist with aripiprazole 5mg by mouth (p.o.) daily for a total of 1.5 years. Two months prior to his ED presentation, aripiprazole had been discontinued because of reported weight gain (1.81 kg in 1.5 years) and ineffectiveness at decreasing aggressive episodes. Lithium CR 300 mg p.o. daily was subsequently started to address the continued aggressive behavior to self and others. One month prior to the ED presentation, guanfacine extended release 2 mg p.o. daily was started. Four days prior to his ED presentation, T.’s psychiatrist had recommended several changes in his medication regimen to target what his mother called ‘‘spasm attacks.’’ These attacks were described by mother as T. hitting and slamming objects, punching holes into walls, attempting to physically harm family members with knives and shovels, and attempting to harm himself by placing his head outside or attempting to get out of a moving car. These symptoms had been escalating over the past few months. Recommended medication changes included discontinuation of guanfacine extended release 2 mg, an increase in lithium CR to 450 mg from 300 mg, and initiation of risperidone 1 mg and lisdexamfetamine (LDX) 50 mg. T.’s mother reportedly did not feel comfortable with the multiple medication changes recommended, so she only stopped the guanfacine extended release and increased the lithium CR. In the 2 days following the lithium CR increase and guanfacine extended release discontinuation, T. reportedly experienced no adverse effects. On the day of his ED presentation, his mother had started the LDX 50 mg in the a.m.; 45 minutes after starting the medication, T.’s mother reported that T. was rubbing his chest and complaining of chest pain. He would not eat, which was very unusual for him, and he reportedly started to gasp for air. T. was taken to a nearby family practice clinic for evaluation. There had been no past history of abnormal movements, shortness of breath, or chest pain.

Conversion from bipolar disorder not otherwise specified (BP-NOS) to bipolar I or II in youth with family history as a predictor of conversion

BackgroundBipolar disorder-not otherwise specified (BD-NOS) is an imprecise, heterogeneous diagnosis that is unstable in youth. This study reports rates of conversion from BD-NOS to BD-I or II in children aged 8–12, and investigates the impact of family history of bipolar disorder and depression on conversion. MethodsAs part of the Multi-Family Psychoeducational Psychotherapy (MF-PEP) study, 27 children (6–12 years of age) diagnosed with BD-NOS at baseline were reassessed every 6 months over an 18-month period. Family history of bipolar disorder and depression was assessed at baseline. ResultsOne-third of the sample converted from BD-NOS to BD-I or II over 18-months. Having a first-degree relative with symptoms of bipolar disorder and having a loaded pedigree for diagnosis of depression each were associated with conversion from BD-NOS to BD-I or II (odds ratio range: 1.09–3.14; relative risk range: 1.06–2.34). LimitationsThis study had very low power (range: 10–45) given the small sample size, precluding statistical significance of non-parametric Fisher's Exact test findings. ConclusionsThis study replicates the previous finding of a high rate of conversion from BD-NOS to BD-I or II among youth, and suggests conversion is related to symptoms of bipolar disorder or depression diagnoses in the family history. Additional research is warranted in a larger sample with a longer follow-up period.

Pilot study of the efficacy of double-blind, placebo-controlled one-week olanzapine stabilization therapy in heterogeneous symptomatic bipolar disorder patients

BackgroundOlanzapine has demonstrated efficacy in acute mania and bipolar I disorder (BDI) maintenance, but efficacy in brief therapy in more diverse populations, including patients with bipolar II disorder (BDII)/bipolar disorder not otherwise specified (BDNOS) with syndromal/subsyndromal depressive/mood elevation symptoms and taking/not taking concurrent medications remains to be established. MethodsFifty adult outpatients (24 BD1, 22 BDII, 4 BDNOS, mean ± SD age 40.8 ± 11.5 years, 28.1% female, already taking 1.1 ± 1.2 [median 1] prescription psychotropics) with 17-item Hamilton Depression Rating Scale (HDRS) ≥10 and/or Young Mania Rating Scale (YMRS) ≥10 and ≤24, were randomized to double-blind olanzapine (2.5–20 mg/day) versus placebo for one week. ResultsAmong 45 patients with post-baseline ratings, olanzapine (9.0 ± 5.8 mg/day, n = 23) compared to placebo (n = 22) tended to yield greater Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (−1.4 ± 0.9 versus −0.8 ± 1.1, p = 0.08) and Hamilton Anxiety Scale (−7.9 ± 6.3 versus −3.8 ± 6.1, p = 0.07) improvements, and YMRS/HDRS remission rate (47.8% versus 22.7%, p = 0.08), but significantly increased median weight (+2 versus −1 lbs, p = 0.001), and rates of excessive appetite (54.2% versus 22.7%, p = 0.04) and tremor (50.0% versus 9.1% p = 0.004). Number Needed to Treat and 95% Confidence Interval for YMRS/HDRS remission were 4 (1–∞). Numbers Needed to Harm for excessive appetite and tremor were 4 (1–21) and 3 (1–6), respectively. ConclusionsOlanzapine tended to yield affective improvement and significantly increased weight, appetite, and tremor. Larger controlled studies appear feasible and warranted to assess brief olanzapine therapy in heterogeneous symptomatic bipolar disorder patients.

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.

Sleep Disturbances in Pediatric Bipolar Disorder: A Comparison between Bipolar I and Bipolar NOS

Introduction: The diagnosis of bipolar disorder (BD) in youths has been controversial, especially for the subtype BD not otherwise specified (BD-NOS). In spite of growing evidence that sleep is a core feature of BD, few studies characterize and compare sleep disturbances in youth with BD type I (BD-I) and BD-NOS. Sleep disturbances are frequently reported in clinical descriptions of children and adolescents with BD, however the reporting of the frequency and characteristics of sleep symptoms in youth with BD-NOS and BD-I during episodes remain poor. This study compares symptom of sleep disturbance as occurring in manic and depressive episodes in BD-I and BD-NOS youth using Kiddie-schedule for affective disorders and schizophrenia, present and lifetime version (K-SADS-PL) interview data. The study also addresses whether symptoms of sleep disturbance vary in different age groups. Materials and Methods: The sample consisted of 70 children and adolescent outpatients at an urban specialty clinic (42M/28F, 10.8 ± 3.6 years old) including 24 BD-I and 46 BD-NOS assessed using K-SADS-PL-parent interview. Results: Sleep disturbances including insomnia and decreased need for sleep were reported by 84.3% of the sample. Enuresis was diagnosed in 27% of sample. There were no significant differences in frequency of sleep symptoms between BD-I and BD-NOS. Regardless of BD subtype, current functioning was negatively correlated with decreased need for sleep but not insomnia, and regardless of BD subtype. Conclusion: The majority of youth with BD presents with sleep symptoms during mood episodes. BD-NOS presents with the same proportion of sleep symptoms as BD-I in our sample.