An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential

Objectives:  Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups.
Methods:  P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM-IV criteria and the Structured Clinical Interview for DSM-IV; and from 56 healthy controls.
Results:  The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups ( F _3,204 = 5.47, p = 0.001, and post-hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group ( F _3,204 = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups.
Conclusions:  The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.     

Short-term course of neuropsychological abilities in middle-aged and older adults with bipolar disorder

Objectives:  There are few longitudinal studies of neurocognition in bipolar disorder, and the short-term course of cognitive deficits in later-life bipolar disorder is unknown.
Methods:  We administered a battery of neurocognitive tests, repeated 1–3 years after baseline, to 35 community-dwelling outpatients with bipolar disorder (mean age = 58), and compared their performance on a composite measure of cognitive functioning to that of demographically matched samples of normal comparison subjects (NCs; n = 35) and patients with schizophrenia (n = 35). Using regression analyses, we examined group differences in baseline performance, trajectory of change over time, and variability in performance across time. Within the bipolar group, we examined the impact of baseline severity and change in severity of psychiatric symptoms on intra-individual change in neurocognitive performance.
Results:  At baseline, the group with bipolar disorder differed in overall neurocognitive functioning from the NCs, but did not differ significantly from the schizophrenia group. The bipolar group did not differ from the NCs or schizophrenia group in the mean trajectory of change between time-points, but the bipolar patients showed more intra-individual variability over time than the NCs or schizophrenia group. In the bipolar group, change in neurocognitive function was not related to baseline or change in psychiatric symptom severity.
Conclusions:  Middle-aged and older community-dwelling adults with bipolar disorder have greater short-term variability in level of neurocognitive functioning relative to NCs or people with schizophrenia. The developmental course of and risk factors for cognitive deficits in bipolar disorder should be examined in future longitudinal studies.     

White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging

Objectives:  Strong qualitative and quantitative evidence exists of white matter abnormalities in both schizophrenia and bipolar disorder (BD). Diffusion tensor imaging (DTI) studies suggest altered connectivity in both disorders. We aim to address the diagnostic specificity of white matter abnormalities in these disorders.
Methods:  DTI was used to assess white matter integrity in clinically stable patients with familial BD (n = 42) and familial schizophrenia (n = 28), and in controls (n = 38). Differences in fractional anisotropy (FA) were measured using voxel-based morphometry and automated region of interest analysis.
Results:  Reduced FA was found in the anterior limb of the internal capsule (ALIC), anterior thalamic radiation (ATR), and in the region of the uncinate fasciculus in patients with BD and those with schizophrenia compared with controls. A direct comparison between patient groups found no significant differences in these regions. None of the findings were associated with psychotropic medication.
Conclusions:  Reduced integrity of the ALIC, uncinate fasciculus, and ATR regions is common to both schizophrenia and BD. These results imply an overlap in white matter pathology, possibly relating to risk factors common to both disorders.     

Oxcarbazepine add-on in the treatment of refractory bipolar disorder

Objective:  To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions.
Methods:  We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales.
Results:  OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 ± 556.11 mg/day and the mean duration of follow-up was 31.60 ± 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects.
Conclusion:  OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.     

Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study

Objective:  Symptoms of bipolar disorder are increasingly recognized among children and adolescents, but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms.
Methods:  We examined prospective outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II outpatients participating in a multicenter clinical effectiveness study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Age at illness onset was identified retrospectively by clinician assessment at study entry.
Results:  Compared to patients with onset of mood symptoms after age 18 years (n = 1,187), those with onset before age 13 years (n = 1,068) experienced earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over the two-year follow-up. Outcomes for those with onset between age 13 and 18 years (n = 1,403) were generally intermediate between these two groups.
Conclusion:  Consistent with previous reports in smaller cohorts, adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence, chronicity of mood symptoms, and functional impairment during prospective observation.     

A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states

Objective:  Asenapine is approved for bipolar disorder and schizophrenia. This was a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for treating acute bipolar mania.
Methods:  After a single-blind placebo run-in period, adults (n = 488) experiencing manic or mixed episodes were randomized to flexible-dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1; 5–20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating Scale (YMRS) total score from baseline to day 21, was assessed using analysis of covariance with last observation carried forward [(LOCF); primary analysis]. A mixed model for repeated measures [(MMRM); prespecified secondary analysis] was also used to assess efficacy. Tolerability and safety assessments included adverse events, physical examinations, extrapyramidal symptom ratings, and laboratory values.
Results:  Mean daily dosages were asenapine 18.2 mg and olanzapine 15.8 mg. Significantly greater least squares (LS) mean ± SE changes in YMRS scores were observed on day 2 with asenapine (−3.0 ± 0.4) and olanzapine (−3.4 ± 0.4) versus placebo (−1.5 ± 0.5, both p < 0.01) and were maintained until day 21 (−10.8 ± 0.8 with asenapine, −12.6 ± 0.8 with olanzapine; both p ≤ 0.0001 versus placebo, −5.5 ± 1.1) with LOCF. The results of MMRM analyses were consistent with those of LOCF. Asenapine had a modest impact on weight and metabolic measures.
Conclusions:  These results indicate that asenapine is rapidly acting, efficacious, and well tolerated for patients with bipolar I disorder experiencing an acute manic episode.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Ten-year diagnostic consistency of bipolar disorder in a first-admission sample

Ruggero CJ, Carlson GA, Kotov R, Bromet EJ. Ten-year diagnostic consistency of bipolar disorder in a first-admission sample.
Bipolar Disord 2010: 12: 21–31. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.
Objectives:  A number of reports have examined the stability of the diagnosis of schizophrenia, but fewer studies have considered the long-term consistency of a bipolar diagnosis or factors that influence the likelihood of a diagnostic change. The present study sought to estimate how consistently a bipolar diagnosis was made across a 10-year period and factors associated with consistency, particularly demographic and clinical characteristics, childhood-related factors, and illness course.
Methods:  The sample included 195 first-admission patients presenting with psychosis who were assessed soon after hospitalization and at 6-month, 2-year, and 10-year follow-up and diagnosed with bipolar disorder on at least one of these assessments. Diagnoses were made using best-estimate procedures and were blind to all previous consensus diagnoses. Respondents who were consistently diagnosed with bipolar disorder were compared to those whose diagnosis shifted across assessments.
Results:  Overall, 50.3% (n = 98) of the 195 respondents were diagnosed with bipolar disorder at every available assessment, but 49.7% (n = 97) had a diagnostic shift to a non-bipolar disorder at least once over the course of the 10-year study. Childhood psychopathology and poorer illness course were among the few variables associated with increased odds of a change in diagnosis.
Conclusions:  Even with optimal assessment practices, misdiagnosis of bipolar disorder is common, with complex clinical presentations often making it difficult to consistently diagnose the disorder over the long term.     

Psychotherapy as monotherapy for the treatment of bipolar II depression: a proof of concept study

Objectives:  We conducted a proof of concept study to determine the feasibility of using an individual psychotherapy, Interpersonal and Social Rhythm Therapy (IPSRT), as monotherapy for the acute treatment of bipolar II depression.
Methods:  Unmedicated individuals (n = 17) meeting DSM-IV criteria for bipolar II disorder and currently depressed received weekly psychotherapy (IPSRT) for 12 weeks. After 12 weeks of acute treatment, individuals received an additional 8 weeks of follow-up treatment consisting of continued weekly IPSRT with supplementary lamotrogine for IPSRT non-responders.
Results:  By week 12, 41% (n = 7) of the sample responded to IPSRT monotherapy (defined as ≥50% reduction in depression scores without an increase in mania scores), 41% (n = 7) dropped out of or were removed from the study, and 18% (n = 3) did not respond to treatment. By week 20, 53% (n = 9) had achieved a response and 29% (n = 5) achieved a full remission of symptoms.
Conclusions:  Interpersonal and Social Rhythm Therapy appears to be a promising intervention for a subset of individuals with bipolar II depression. A randomized controlled trial is needed to systematically evaluate the efficacy of IPSRT as an acute monotherapy for bipolar II depression.     

Clinical characteristics of unipolar disorder and bipolar disorder according to the lifetime presence of recurrent panic attacks

Objectives:  The frequent comorbidity of panic and affective disorders has been described in previous studies. However, it is not clear how panic disorder comorbidity in unipolar disorder and bipolar disorder is related to illness course.
Methods:  We compared lifetime clinical characteristics of illness and items of symptomatology in samples of individuals with bipolar I disorder (n = 290) and unipolar disorder (n = 335) according to the lifetime presence of recurrent panic attacks.
Results:  We found significant differences in clinical course of illness characteristics that were shared across the unipolar and bipolar samples according to the lifetime presence of panic attacks. We also found a number of differences according to the presence of panic attacks that may be specific to the diagnostic group.
Conclusions:  Distinguishing patients who have mood disorder diagnoses, especially bipolar I disorder, according to the lifetime presence of panic attacks may not only be of use in clinical practice, but may also be informative for aetiological research, such as molecular genetic studies.