Fronto-limbic brain abnormalities in juvenile onset bipolar disorder.

BACKGROUND: Advances in brain imaging techniques and cognitive neuropsychology have brought new possibilities for the in vivo study of the pathophysiology of neuropsychiatric disorders, including bipolar disorder (BD). Recently, such studies have been extended to the pediatric age range. Here we review the neuroimaging and neuropsychological studies conducted in BD children and adolescents. METHODS: A review of the peer-reviewed published literature was conducted in Medline for the period of 1966 to April 2005. RESULTS: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies suggest abnormalities in fronto-limbic structures in pediatric BD patients, similar to those found in adults. A notable exception in pediatric BD patients is smaller amygdala volumes compared to healthy controls, contrary to what has been reported in most adult studies. CONCLUSIONS: Further research evaluating children and adolescents is needed to study the normal neurodevelopmental process and to answer how and when the illness processes that result in bipolar disorder exert their effects on the developing brain.     

Differences between prepubertal- versus adolescent- onset bipolar disorder in a Spanish clinical sample

Objective To examine patients attended and diagnosed with bipolar disorder (BD) at a child and adolescent psychiatry service; to record age of diagnosis and age of onset, and to study clinical differences between prepubertal and adolescent onset groups. Methods All patients currently attended for BD type I, type II or non specified BD were reviewed and divided into two age groups: prepubertal onset (beginning before age 13) and adolescent onset (beginning at or above age 13). Results The sample were 43 patients with BD. Fourteen (32.6%) with prepubertal onset and 29 (67.4%) with adolescent onset. Time between onset of symptoms and diagnosis was longer in the prepubertal onset group (1.2 years versus 0.8 years respectively, P = .05). Patients with prepubertal onset BD more frequently presented previous symptoms such as irritability and conduct problems and had a higher rate of comorbidity (more frequently attention-deficit/hyperactivity disorder–ADHD). The adolescent onset group more often presented psychotic symptoms. Conclusion The clinical characteristics of patients with bipolar disorder differ according to whether onset is prepubertal or adolescent.     

Juvenile bipolar disorder

OBJECTIVE: Bipolar disorder in children and adolescents is less well studied than bipolar disorder in adults. This review addresses issues related to its underdiagnosis, precursors of bipolarity, comorbidity, natural course and treatment. METHOD: Literature from Medline and other searches, and earlier relevant articles including references from recent review articles on juvenile bipolarity were reviewed. RESULTS: Bipolar disorder in juveniles is underdiagnosed and misdiagnosed on various counts. Few recent studies have reported high rates of comorbid attention deficit and disruptive disorders, prompting some researchers to consider them as probable developmental precursors of juvenile bipolarity. There is also evidence to suggest that some juvenile depression could be pre-bipolar, and that certain temperamental predispositions are probable precursors to bipolarity. Limited data on the natural course and outcome suggest that juvenile bipolar disorder is a highly recurring illness as in adults, and that it is associated with significant functional impairment. The psychopharmacological treatment of juvenile bipolar disorder is remarkably understudied, and treatment is often based on studies of adults. CONCLUSION: There is a need for epidemiological studies of juvenile bipolar disorder. Similarly, there is an urgent need for the methodologically rigorous studies to establish the efficacy of various antimanic drugs. Finally, issues related to comorbidity and temperamental predispositions to juvenile bipolarity need greater clarity, as they may have important treatment and research implications.     

The genetics of pediatric-onset bipolar disorder.

Although bipolar disorder in adults has been extensively studied, early-onset forms of the disorder have received less attention. We review several lines of evidence indicating that pediatric- and early adolescent-onset bipolar disorder cases may prove the most useful for identifying susceptibility genes. Family studies have consistently found a higher rate of bipolar disorder among the relatives of early-onset bipolar disorder patients than in relatives of later-onset cases, which supports the notion of a larger genetic contribution to the early-onset cases. Comorbid pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) may also define a familial subtype of ADHD or bipolar disorder that is strongly influenced by genetic factors and may, therefore, be useful in molecular genetic studies. There are no twin and adoption studies of pediatric bipolar disorder, but the heritability of this subtype is expected to be high given the results from family studies. Thus, pediatric- and early adolescent-onset bipolar disorder may represent a genetically loaded and homogeneous subtype of bipolar disorder, which, if used in genetic linkage and association studies, should increase power to detect risk loci and alleles.     

A prospective 4-5 year follow-up of juvenile onset bipolar disorder

OBJECTIVE: Data on outcome of juvenile onset bipolar disorder is limited. This study examined the course and outcome of bipolar disorder and assessed the rate and predictors of recovery and relapse in a sample of children and adolescents over a 4-5 year period. METHOD: Twenty-five consecutively ascertained subjects (9-16 years) with a diagnosis of mania (mean duration at intake of 4.6 +/- 3.9 weeks), were comprehensively assessed at baseline and at 6-month intervals using the Diagnostic Interview for Children and Adolescents (revised) (DICA-R), the Missouri Assessment for Genetic Interview in Children (MAGIC), the Young's Mania Rating Scale (YMRS) and the Children's Global Assessment (CGAS). The study phenotype required DSM-IV criteria of mania with elation and/or grandiosity as a criterion to distinguish them from those with attention deficit hyperactivity disorder. Subjects received the standard treatment as prescribed by their primary treating team. RESULTS: During the course of the study period, all 25 subjects (100%) recovered from the index episode. The mean time to recovery was 44 +/- 46 days. The mean duration of follow-up was 51.6 +/- 4.1 months. Sixteen subjects (64%) relapsed after a mean period of 18 +/- 16.4 months. A majority of the relapses (72.4%) were while the subjects were on treatment. CONCLUSIONS: Acute juvenile onset mania has a high rate of recovery and low chronicity. The relapse rate was high and most of these occurred in the first 3 years despite aggressive prophylactic treatment. The effectiveness of currently used thymoleptics, in particular lithium, in the prophylaxis of juvenile bipolar disorder needs to be evaluated in controlled studies.     

Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study

Objectives:  To evaluate the efficacy, safety, and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder.
Methods:  This randomized, placebo-controlled, double-blind, 3-arm study (N = 169) included children and adolescents (ages 10–17 years) with a DSM-IV diagnosis of bipolar I disorder, experiencing a manic or mixed episode. Study participants were randomized to placebo (n = 58), risperidone 0.5–2.5 mg/day (n = 50), or risperidone 3–6 mg/day (n = 61) for 3 weeks. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) total score from baseline to end point. Safety assessments included adverse event (AE) monitoring and scores on extrapyramidal symptom rating scales.
Results:  Improvement in mean YMRS total score was significantly greater in risperidone-treated subjects than in placebo-treated subjects [mean change (SD) −9.1 (11.0) for placebo; −18.5 (9.7) for risperidone 0.5–2.5 mg (p < 0.001); −16.5 (10.3) for risperidone 3–6 mg (p < 0.001)]. The most common risperidone-associated AEs were somnolence, headache, and fatigue. Mean (SD) weight gain was 0.7 (1.9) kg, 1.9 (1.7) kg, and 1.4 (2.4) kg in the placebo, risperidone 0.5–2.5 mg, and risperidone 3–6 mg groups, respectively, during this 3-week study.
Conclusions:  At daily doses of 0.5–2.5 mg and 3–6 mg, risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder. Results indicate that risperidone 0.5–2.5 mg has a better benefit–risk profile than risperidone 3–6 mg.     

Combination pharmacotherapy in children and adolescents with bipolar disorder.

BACKGROUND: The purpose of this study was to develop prospective data on the effectiveness of combination pharmacotherapy of children and adolescents with bipolar disorder during a 6-month period of prospective, semi-naturalistic treatment. METHODS: Thirty-five subjects, with a mean age of 11 years, were treated in the extension phase of this study after having received 6-8 weeks of acute treatment with a single mood stabilizer. The extension phase of this study lasted for another 16 weeks, for a total of 24 weeks of prospective treatment. During this study phase, subjects were openly treated, and they could have their acute-phase mood stabilizer switched or augmented with another mood stabilizer, a stimulant, an antidepressant agent, or antipsychotic agent, if they were assessed to be a nonresponder to monotherapy with their initial mood stabilizer. RESULTS: During the extension phase of treatment, 20 of 35 subjects (58%) required treatment with one or two mood stabilizers and either a stimulant, an atypical antipsychotic agent, or an antidepressant agent. The response rate to combination therapy was very good, with 80% of subjects treated responding to combination therapy with two mood stabilizers after not responding to monotherapy with a mood stabilizer. CONCLUSIONS: This study suggests that children and adolescents with bipolar disorder are similar to adults with bipolar disorder, who also frequently require combination therapy.     

Asenapine: a review of acute and extension phase data in bipolar disorder

The second generation atypical antipsychotic, asenapine (Saphris), was approved by the US FDA (August 2009) for the acute treatment of manic or mixed episodes with or without psychotic features associated with bipolar I disorder in adults as well as the acute treatment of schizophrenia. Asenapine exhibits a high affinity for and antagonism at several serotonergic (5-HT(2A-C), 5HT(5A), 5HT(6), 5HT(7)), dopaminergic (D(2), D(3)), alpha-adrenergic (α(1) and α(2)), and histaminergic (H1, H2) receptor subtypes. Asenapine is the first atypical antipsychotic formulated as a fast-dissolving, rapidly absorbed sublingual tablet. Asenapine was evaluated in adults with bipolar I disorder, manic or mixed episodes with or without psychotic features. Two identically designed 3-week registration trials confirmed the efficacy of asenapine relative to placebo in studies that included olanzapine as an active control. The placebo-subtracted rate of EPS (excluding akathisia) is 5% whereas the placebo-subtracted rate of akathisia was 2%. The placebo-subtracted rate of clinically significant weight gain (≥7%) with asenapine was approximately 5% during the 3-week acute mania trials. A 9- extension trial indicated that 19% of asenapine patients will experience clinically significant weight gain. Clinically significant metabolic abnormalities were not observed during the acute and/or extension trials. Asenapine can be associated with somnolence (asenapine 24%, placebo 6%) and does not appear to be associated with clinically significant changes in vital signs, laboratory parameters, or electrocardiographic changes. Bipolar depression and recurrence prevention studies are required to fully characterize this novel agent's position in the treatment of bipolar disorder.     

Initiation of stimulant and antidepressant medication and clinical presentation in juvenile bipolar I disorder

OBJECTIVES: The primary purpose of this study was to examine the extent to which the initiation of stimulant and antidepressant medication was associated with the subsequent onset of juvenile bipolar I disorder (BP I). Another aim was to investigate differences in clinical presentation between youths prescribed stimulant or antidepressant medication before and after the onset of juvenile BP I disorder. METHODS: Youths between the ages of 5 and 17 years meeting full, unmodified DSM-IV diagnostic symptom criteria for BP were included in this study. Data regarding the age of onset of BP I, psychiatric comorbidities, and current symptoms of mania and depression were obtained. Medication history was recorded as part of the assessment interview with parents and youths. RESULTS: Of the 245 youths with BP I, 65% (n = 160) were treated with stimulant medication; 32% (56/173) were treated after the onset of BP I, and 19% (32/173) were treated before the onset of BP I. Forty-six percent (113/245) were treated with antidepressant medication; 33% (67/206) were treated after the onset of BP I, and 3% (7/206) were treated before the onset of BP I. Patients who were treated with stimulants after the onset of BP I were significantly more likely to be younger (p < 0.0001). Patients who were treated with antidepressants before the onset of BP I were significantly more likely to be older and to have lower levels of mania on the Young Mania Rating Scale at assessment (p < 0.01). CONCLUSIONS: Data from this retrospective case series do not support the association between initial stimulant or antidepressant use and the onset of BP I or presenting symptoms of depression or manic symptoms.     

Comorbidity of attention deficit hyperactivity disorder in juvenile bipolar disorder

OBJECTIVE: There is some evidence to suggest that attention deficit hyperactivity disorder (ADHD) and juvenile bipolar disorder could be related. This is based on studies of comorbidity and some preliminary family study data. However, doubts continue to be raised about the relationship between the two disorders. This study examined the comorbidity of disruptive behavior disorders (DBD) that include ADHD, oppositional defiant disorder (ODD) and conduct disorder (CD) in juvenile bipolar disorder. METHOD: Seventy-three subjects with onset of bipolar disorder at age 18 years or younger were evaluated using structured interviews (Missouri Assessment of Genetics Interview for Children, Structured Clinical Interview for DSM-IV Axis I disorders--Clinician Version, and Operational Criteria Checklist for Psychotic Disorders version 3.4). Information was collected from subjects as well as from their parents. Patients with comorbid DBD were compared with patients without DBD. RESULTS: Ten subjects (14%) had one or more comorbid DBD. ADHD, CD, and ODD were present in three (4%), two (3%), and eight (11%) subjects, respectively. Those with DBD had earlier onset of bipolar disorder and spent more time ill compared to those without DBD. CONCLUSIONS: The rates of comorbid DBD in juvenile bipolar disorder are low. The study does not support a definite relationship between ADHD and juvenile bipolar disorder. Higher rates reported previously may be due to differing methods of subject ascertainment. Samples recruited from community and general psychiatric settings may help to clarify the relationship between bipolar disorder and ADHD.     

Verapamil treatment for women with bipolar disorder.

BACKGROUND: Additional pharmacological treatments are needed for patients with bipolar disorder. We describe our experience with verapamil in an inclusive, sequential series of outpatient women (some pregnant) with bipolar disorder. METHODS: All women who were prescribed verapamil for bipolar disorder (n = 37) were included. We used the criterion of 50% reduction in scores on the Mania Rating Scale or the Hamilton Rating Scale for Depression to define response for women who were treated for an acute episode of bipolar hypomania/mania or depression, respectively. For euthymic women who chose verapamil maintenance treatment, we evaluated whether they met criteria for a recurrent episode during therapy. RESULTS: Treatment for acute episodes was initiated in 28 women. Of women with depression and mania, 39% and 100% responded, respectively. Seven of the nine patients (77%) with mixed states responded: all seven improved to response criterion on the mania scale, and two responded on the depression scales as well. Six of eight patients who received continuation therapy remained well. CONCLUSIONS: These data provide evidence that verapamil is effective for mania. The response rate for mania compares favorably to that for other mood stabilizers. After decades of case reports and underpowered clinical trials, we must definitively study verapamil for efficacy and gender specificity in bipolar disorder.     

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.

BACKGROUND: Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI). METHODS: We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions. Twenty-six studies comprising volumetric measurements on up to 404 independent patients with bipolar disorder were included. A meta-analysis was carried out comparing the volumes of regions in bipolar disorder to comparison subjects using a random effects model. RESULTS: Patients with bipolar disorder had enlargement of the right lateral ventricle, but no other regional volumetric deviations which reached significance. Strong heterogeneity existed for several regions, including the third ventricle, left subgenual prefrontal cortex, bilateral amygdala and thalamus. CONCLUSIONS: Regional volume of most structures we studied is preserved in bipolar disorder as a whole, which was significantly associated only with right-sided ventricular enlargement. However the extensive heterogeneity detected indicates the need for further studies to establish if consistent regional brain volume deviation exists in bipolar disorder or in specific clinical subsets of the illness.     

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.     

Social anxiety disorder comorbidity in patients with bipolar disorder: a clinical replication

BACKGROUND: The authors investigated frequency, clinical correlates and onset temporal relationship of social anxiety disorder (SAD) in adult patients with a diagnosis of bipolar I disorder. METHODS: Subjects were 189 patients whose diagnoses were assessed by the Structured Clinical Interview for DSM-III-R-Patient Version. RESULTS: Twenty-four patients (12.7%) met DSM-III-R criteria for lifetime SAD; of these, 19 (10.1% of entire sample) had SAD within the last month. Significantly more bipolar patients with comorbid SAD also had substance use disorders compared to those without. On the HSCL-90, levels of interpersonal sensitivity, obsessiveness, phobic anxiety and paranoid ideation were significantly higher in bipolar patients with SAD than in those without. Bipolar patients with comorbid SAD recalled separation anxiety problems (school refusal) more frequently during childhood than those without. Lifetime SAD comorbidity was associated with an earlier age at onset of syndromal bipolar disorder. Pre-existing OCD tended to delay the onset of bipolarity. CONCLUSIONS: Social anxiety disorder comorbidity is not rare among patients with bipolar disorder and is likely to affect age of onset and phenomenology of bipolar disorder. These findings may influence treatment planning and the possibility of discovering a pathophysiological relationship between SAD and bipolarity.     

Clinical implications of pervasive manic symptoms in children.

BACKGROUND: Prior investigations of cross-informant agreement among parents, teachers, and clinicians about externalizing and internalizing problems have not directly addressed agreement about manic symptoms. METHODS: We identified three groups from a large cohort of youths, aged 8-12 years, treated on an inpatient unit. All 108 participants met criteria for an externalizing disorder, based on a semi-structured diagnostic interview. Of these, 49 did not have manic symptoms endorsed by either the parent or a teacher; 34 had manic symptoms reported by the parent only, and 25 had pervasive manic symptoms (i.e., corroborated by both sources). RESULTS: The "corroborated mania" group consistently showed the most disruptive behavior on the inpatient unit, the worst behavior problems on multiple scales, and the longest admission durations. The "parent-only" group scored in the midrange on all of these measures, with group differences typically representing small to medium effect sizes. The "externalizing only" group consistently scored lowest on all dependent measures, with the differences representing large to extremely large effects when compared with the corroborated mania group and medium effects as compared with the parent-only group. CONCLUSIONS: Youths for whom multiple informants report manic symptoms appear likely to have more severe symptom presentation and more complicated, refractory courses than do youths without manic symptoms.     

Late-onset bipolar disorder due to hyperthyroidism.

OBJECTIVE: Bipolar disorder starts typically in early age and late-onset cases are rare. Late-onset cases are more likely to have comorbid medical illnesses responsible for them. This case report highlights late-onset bipolar disorder due to hyperthyroidism. METHOD: A 65-year-old patient of bipolar disorder has been described. RESULT: Physical examination and laboratory investigations detected presence of hyperthyroidism and the patient was treated with antithyroid and anxiolytics. CONCLUSION: A thorough examination and investigation are required in late-onset cases of bipolar disorder to rule out secondary causes. Definitive antimanic agents or mood stabilizers may not be required in such cases.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

Objective

To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method

Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion

In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder

OBJECTIVES: To examine the rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder (BD). METHODS: Adolescents (n = 80), between the ages of 12 and 21 years (mean = 15.6, standard deviation = 2.3), hospitalized for their initial manic or mixed episode of BD, were evaluated for the incidence of prior juvenile offending (i.e., legal charges). We examined potential psychosocial correlates associated with legal charges using chi-square, t-tests, and discriminant function analyses to determine if there were differences between adolescents who did and did not offend prior to their first manic episode. RESULTS: Juvenile antisocial behaviors were common (55%) for adolescents with newly diagnosed BD. Discriminant function analysis revealed that older age at first treatment (p < 0.01), sexual activity over the previous month (p < 0.05), therapeutic use of stimulants (p < 0.05), and anxiety disorders were the most significant factors to differentiate between bipolar adolescents who offended and those who did not (Wilks' lambda = 0.80, p < 0.005). CONCLUSIONS: Our findings indicate that there are identifiable psychosocial correlates associated with antisocial behaviors in adolescents with newly diagnosed BD that may improve our understanding of juvenile antisocial behaviors.     

A preliminary meta-analysis of the child behavior checklist in pediatric bipolar disorder.

BACKGROUND: A possible explanation for the ongoing controversy surrounding pediatric bipolar disorder is that differences in assessment methodologies lead to conflicting results. One way to address methodological differences in assessment across studies is to use a single standardized assessment of psychopathology to calibrate the findings reported in different studies. To this end, we conducted a meta-analysis of several studies that have employed the Child Behavior Checklist in the assessment of children with a diagnosis of bipolar disorder. METHODS: MEDLINE was searched for all publications that utilized the Child Behavior Checklist in addition to structured diagnostic interviews to assess pediatric bipolar disorder. Random effects models were used to calculate combined estimates of Child Behavior Checklist clinical subscales. RESULTS: Children with bipolar disorder had scaled scores of >70 in the Aggression, Attention Problems, and Anxious/Depressed subscales of the Child Behavior Checklist. The Child Behavior Checklist was useful in distinguishing bipolar from attention-deficit/hyperactivity disorder subjects. CONCLUSIONS: While there was a significant heterogeneity in estimates between studies, a consistent pattern of elevations in inattention/hyperactivity, depression/anxiety, and aggression was identified.     

Association of clinical symptoms and neurocognitive performance in bipolar disorder: a longitudinal study

Chaves OC, Lombardo LE, Bearden CE, Woolsey MD, Martinez DM, Barrett JA, Miller AL, Velligan DI, Glahn DC. Association of clinical symptoms and neurocognitive performance in bipolar disorder: a longitudinal study.
Bipolar Disord 2011: 13: 118–123. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: Despite evidence that individuals with bipolar disorder have neurocognitive impairment that persists during euthymia, the impact of changes in affective symptoms on cognitive function has not been well established. Here, we sought to determine whether specific neurocognitive functions are sensitive to mood changes in individuals with bipolar disorder assessed three months apart without changes in treatment regimen. Methods: A total of 29 individuals with DSM‐IV bipolar disorder and 30 healthy controls participated in the study. All participants received a comprehensive neuropsychological assessment and ratings of depressive [Hamilton Depression Rating Scale (HAMD)] and manic [Young Mania Rating Scale (YMRS)] symptoms at baseline and follow‐up. Changes in symptoms over time were calculated and were examined in relation to changes in neurocognitive performance. Results: At baseline, clinically stable but symptomatic patients were impaired on measures of speed of processing and attention. Over the three‐month follow‐up period, HAMD scores changed by 6 points on average [range: ?10 to +18] and YMRS scores changed by 5.31 points on average [range ?11 to +15]. Changes in depressive symptoms were correlated with poorer verbal fluency, while no relationship between manic symptoms and neuropsychological performance was detected. Conclusions: Individuals with bipolar disorder showed consistent impairment on speed of processing and attention over time, despite significant changes in mood.