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Caleb M Adler

Publications and source records attributed to Caleb M Adler.

At least 19 recordsLinked to original sources

Effects of co-occurring cannabis use disorders on the course of bipolar disorder after a first hospitalization for mania.

CONTEXT: Cannabis use disorders commonly co-occur in bipolar disorder; however, the effects of cannabis abuse on outcome have been minimally studied. OBJECTIVE: To identify how the sequence of the onsets of a cannabis use disorder and bipolar disorder is associated with the subsequent course of each condition. DESIGN: Inception cohort. SETTING: Academic medical center. PATIENTS: Patients (N = 144) were studied who met criteria for bipolar I disorder (manic or mixed), were 12 to 45 years old, and had no previous hospitalizations and minimal previous treatment. Patients were followed up for up to 5 years and included 33 in whom the onset of a cannabis use disorder preceded the onset of bipolar disorder (cannabis first), 36 in whom bipolar disorder onset preceded the onset of cannabis abuse (bipolar first), and 75 with bipolar disorder only. MAIN OUTCOME MEASURES: Symptomatic recovery and recurrence of both conditions and percentage of follow-up time with affective and cannabis use disorder symptoms. RESULTS: The cannabis first group exhibited better recovery than the other groups, although when adjusted for potential mediator variables these results did not persist. Cannabis use was associated with more time in affective episodes and with rapid cycling. Most cannabis use disorders remitted immediately after hospitalization, followed by rapid rates of recurrence. CONCLUSIONS: The effects of the sequence of onsets of bipolar and cannabis use disorders were less pronounced than observed in co-occurring alcohol and bipolar disorders. Aggressive drug abuse treatment immediately after a first psychiatric hospitalization might decrease rates of recurrence and new cases of cannabis use disorder in the course of bipolar disorder.

Adolescent↗

Lithium treatment effects on Myo-inositol in adolescents with bipolar depression.

BACKGROUND: The neurochemical effects of lithium in adolescents with bipolar disorder largely are unknown. This study used proton magnetic resonance spectroscopy (1H MRS) to identify the in vivo effects of lithium on myo-inositol (mI) concentrations in adolescent bipolar depression. METHODS: Twenty-eight adolescents (12-18 years old) with bipolar I disorder, current episode depressed, received open-label lithium 30 mg/kg, adjusted to achieve serum levels of 1.0-1.2 mEq/L. The mI concentrations in the medial as well as the left and right lateral prefrontal cortices were measured at baseline, day 7, and day 42 of treatment. Changes in mI concentrations over time were analyzed. RESULTS: Significant main effects of time were observed for mI concentrations in the medial (p = .03) and right lateral (p = .05) prefrontal cortices. Baseline concentrations of mI were not significantly different from day 7 or day 42 concentrations. However, mI concentrations on day 42 were significantly higher than those on day 7 (p = .02) in both regions. CONCLUSIONS: This study demonstrates that prefrontal mI concentrations do not significantly change from baseline after acute and chronic lithium treatment in adolescents with bipolar depression. Further investigation of the effect of lithium on mI is warranted to better understand possible mechanisms by which lithium exerts antidepressant activity.

Adolescent↗

Voxel-based study of structural changes in first-episode patients with bipolar disorder.

BACKGROUND: Although morphometric studies of bipolar disorder (BD) suggest that neurofunctional abnormalities reflect underlying structural changes, it remains unclear whether abnormalities are present at illness onset or reflect disease progression. Previous voxel-based morphometry (VBM) findings suggest that ventrolateral prefrontal cortex (VLPFC) changes develop over time, whereas morphologic abnormalities elsewhere in the anterior limbic network (ALN) are present early in BD. In this study, we used VBM to explore structural brain changes in first-episode bipolar patients. METHODS: First-episode bipolar (n = 33) and healthy (n = 33) subjects underwent magnetic resonance imaging. Images were normalized and compared on a voxel-by-voxel basis. RESULTS: Bipolar subjects showed no change in VLPFC density or volume. We observed increased volume in left thalamus and fusiform and cerebellum bilaterally; increased gray matter density in anterior cingulate and posterior parietal structures; and increased gray matter volume and density in middle/superior temporal and posterior cingulate gyri. No areas of decreased volume or density were observed. CONCLUSIONS: These data indicate that structural changes are absent from VLPFC early in the course of BD. Morphologic abnormalities are present in other portions of the ALN and in structures previously observed to mediate neurofunctional changes in BD, suggesting that dysfunctional neuronal proliferation or pruning may occur in bipolar patients.

Adolescent↗

The neurophysiology of childhood and adolescent bipolar disorder.

INTRODUCTION: Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early- and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course. METHODS: Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed. RESULTS: Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder. CONCLUSION: Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.

Adolescent↗

Brain network dysfunction in bipolar disorder.

Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.

Affect↗

Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a proton magnetic resonance spectroscopy study.

We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment remitters and nonremitters. Secondary aims of this study were to identify neurochemical predictors of successful olanzapine treatment and other neurochemical effects of olanzapine. In all, 20 adolescents admitted for their first hospitalization for bipolar disorder, type I, manic or mixed and 10 demographically matched healthy subjects were recruited. Manic adolescents were treated with olanzapine monotherapy and scanned at three time points (N = 19). Medial and left and right lateral ventral prefrontal NAA, choline, creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at baseline, prior to receiving medication, and on days 7 and 28 of treatment. Healthy subjects did not receive medication but underwent 1H MRS scans at the same time points to assess for normal variability in metabolites over time. Although there was no overall increase in NAA in manic adolescents following 28 days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a greater increase in medial ventral prefrontal NAA compared with nonremitters (N = 8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic adolescents treated with olanzapine had an increase from baseline to day 7 in medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline. Baseline medial ventral prefrontal choline was greater in olanzapine remitters than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine may lead to increased ventral prefrontal neuronal viability and/or function as compared to unsuccessful treatment with olanzapine. Additionally, olanzapine-induced increases in choline may lead to alteration of abnormalities in cell membrane metabolism or second messenger pathways that are thought to be involved in the pathophysiology of bipolar disorder.

Adolescent↗

The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s).

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders. METHOD: Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point. RESULTS: Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28]. CONCLUSIONS: Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.

Adolescent↗

A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania.

OBJECTIVE: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. METHOD: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days for this double-blind study, which was conducted from July 2002 through January 2004. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) score across the study period. RESULTS: Repeated measures analysis of variance using the last-observation carried forward data indicated no statistically significant group difference in YMRS scores across the 28 days of the study (p = 0.3). Mixed regression analyses (comparison of slopes) revealed that improvement in YMRS scores occurred more rapidly in the quetiapine than in the divalproex group for both the last-observation carried forward (p = 0.01) and observed data (p = 0.03). Response and remission rates were significantly greater in the quetiapine than in the divalproex group (p < .03). Rates of adverse events did not differ significantly between groups. CONCLUSIONS: The results suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms associated with adolescent bipolar disorder; however, a quicker reduction of manic symptoms may occur with quetiapine as compared with divalproex. Quetiapine may be useful as monotherapy for the treatment of adolescents with manic or mixed episodes, although placebo-controlled studies are necessary.

Adolescent↗

Open-label lithium for the treatment of adolescents with bipolar depression.

OBJECTIVES: To investigate the effectiveness and tolerability of lithium for the treatment of acute depression in adolescents with bipolar disorder. We hypothesized that patients receiving open-label treatment with lithium during a 6-week period would experience a statistically and clinically significant decrease in depressive symptoms and tolerate lithium treatment fairly well. METHOD: Twenty-seven adolescents (12-18 years old) with an episode of depression associated with bipolar disorder type I received open-label lithium 30 mg/kg (twice-daily dosing), which was adjusted to achieve a therapeutic serum level (1.0-1.2 mEq/L). Effectiveness measures included the Children's Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP). Adverse events were assessed weekly. RESULTS: Mean CDRS-R scores significantly decreased from baseline to endpoint (mean [SD] change = -25.5 (20.4); p < .001), resulting in a large effect size of 1.7. Response and remission rates (defined by a > or = 50% reduction in CDRS-R score from baseline to endpoint, and a CDRS-R score < or = 28 and a CGI-BP Improvement score of 1 or 2, respectively) were 48% and 30%. Side effects, which were generally mild to moderate in severity, included headache (74%), nausea/vomiting (67%), stomachache (30%), and abdominal cramps (19%). CONCLUSIONS: The findings of this study indicate that lithium may be effective and is relatively well tolerated for the treatment of an acute episode of depression in adolescents with bipolar disorder. Controlled studies of lithium in adolescent bipolar depression are needed.

Adolescent↗

Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study.

OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions that bipolar disorder is characterized by subtle white matter changes. The chronic nature of the study population, however, has limited interpretation of these findings. In this study the authors utilized diffusion tensor imaging to study white matter tracts of adolescents in their first episode of mania to address whether abnormalities are present in early bipolar disorder. METHOD: Eleven medication-naive adolescents in their first episode of mania and 17 healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy and trace apparent diffusion coefficients of prefrontal and posterior regions of interest were compared between groups. RESULTS: Bipolar adolescents showed significantly decreased fractional anisotropy only in superior-frontal white matter tracts. Trace apparent diffusion coefficients did not significantly differ in any regions examined. CONCLUSIONS: These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.

Adolescent↗

Changes in gray matter volume in patients with bipolar disorder.

BACKGROUND: Several lines of evidence suggest the presence of neurofunctional abnormalities in patients with bipolar disorder. These functional abnormalities may stem from structural pathology in these or connected brain regions. Previous studies have generally used a region of interest (ROI) approach to study morphologic changes in bipolar disorder with inconsistent findings among research groups, which may reflect differences in how ROIs are defined. Voxel based morphometry (VBM) allows a more exploratory analysis without the necessity for predefined anatomic boundaries. In this study we utilized VBM to compare gray matter volume between groups of bipolar and healthy subjects. METHODS: Thirty-two patients with bipolar disorder and 27 healthy subjects participated in structural magnetic resonance imaging (MRI) scans. MRI images were segmented, normalized to a standard stereotactic space, and compared on a voxel-by-voxel basis using statistical parametric mapping. RESULTS: Bipolar subjects showed increased gray matter in several regions including portions of anterior cingulate, ventral prefrontal cortex, fusiform gyrus and parts of the primary and supplementary motor cortex. Bipolar subjects showed decreased gray matter volume in superior parietal lobule. CONCLUSIONS: These data support suggestions that neurofunctional deficits are related to structural brain abnormalities in patients with bipolar disorder. The increased gray matter observed in several regions suggests that some affected areas may demonstrate volumetric expansion, at least in some patient populations.

Adult↗

Effects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania.

CONTEXT: Alcohol-use disorders are common co-occurring conditions affecting bipolar patients, and this co-occurrence is negatively associated with outcome. OBJECTIVE: The primary goal of this study was to identify how the relative onsets of alcohol-use and bipolar disorders affect the subsequent courses of illness in patients with both conditions. DESIGN AND SETTING: Inception cohort at an academic medical center. PATIENTS: Patients meeting criteria for type I bipolar disorder, manic or mixed, with ages of 12 to 45 years, no prior hospitalizations, and minimal prior treatment. We enrolled 144 subjects who were followed up for up to 5 years, including 27 subjects in whom the onset of an alcohol-use disorder preceded the onset of bipolar disorder (Alcohol First), 33 subjects in whom bipolar disorder onset preceded or was concurrent with the onset of alcohol abuse (Bipolar First), and 83 subjects with bipolar disorder only (No Alcohol). MAIN OUTCOME MEASURES: Symptomatic recovery and recurrence of both conditions and percentage of follow-up with affective episodes and affective and alcohol-use disorder symptoms. RESULTS: The Alcohol First group was older and more likely to recover and recover more quickly than the other groups. Affective symptomatic recurrence curves were similar among groups. The Bipolar First group spent more time with affective episodes and symptoms of an alcohol-use disorder during follow-up than the Alcohol First group. Hospitalization was associated with a period of decreased alcohol abuse, although recurrence of the alcohol-use disorder was common. CONCLUSIONS: The relative age at onset of alcohol-use and bipolar disorders is associated with differences in the course of both conditions. A first hospitalization for mania is associated with a period of recovery from comorbid alcohol abuse, suggesting this posthospital time may provide an opportunity to treat this co-occurring condition.

Adult↗

Comorbid ADHD is associated with altered patterns of neuronal activation in adolescents with bipolar disorder performing a simple attention task.

OBJECTIVES: Bipolar disorder is increasingly recognized as a significant source of psychiatric morbidity in children and adolescents. Younger bipolar patients symptomatically differ from adults, and frequently present with comorbid disorders, particularly attention-deficit hyperactivity disorder (ADHD). The neurophysiological relationship between these two disorders, however, remains unclear. In this study we utilized functional magnetic resonance imaging (fMRI) to compare activation patterns during performance of a simple attention task between bipolar adolescents with and without ADHD. METHODS: Eleven bipolar adolescents with comorbid ADHD and 15 bipolar adolescents without comorbidity were recruited to participate in fMRI scans. A single-digit continuous performance task alternated with a control task in a block-design paradigm. between-group comparisons were made using voxel-by-voxel analysis. Follow-up correlations were made between performance and activation. RESULTS: Group performance did not significantly differ in percentage correct (p = 0.36) or discriminability (p = 0.11). ADHD comorbidity was associated with less activation in the ventrolateral prefrontal cortex (Brodmann 10) and anterior cingulate, and greater activation in posterior parietal cortex and middle temporal gyrus. Comorbid ADHD was associated with substantial differences in patterns of correlation between performance and voxel-by-voxel activation. CONCLUSIONS: Our findings suggest that comorbid ADHD in bipolar adolescents is associated with activation of alternative pathways during performance of a simple attention task. The pattern of differences suggests that bipolar adolescents with comorbid ADHD demonstrate decreased activation of prefrontal regions, compared with bipolar adolescents without ADHD, and preferentially recruit portions of posterior parietal and temporal cortex.

Adolescent↗

MRI analysis of cerebellar vermal abnormalities in bipolar disorder.

OBJECTIVE: The authors sought to expand previous findings of vermal abnormalities in bipolar disorder patients. METHOD: Magnetic resonance imaging (MRI) morphometry was used to quantify vermal subregion volumes in 18 subjects with first-episode bipolar disorder, 21 subjects with multiple-episode bipolar disorder, and 32 healthy subjects. RESULTS: Vermal subregion V2 volume was significantly smaller in multiple-episode bipolar disorder subjects than in first-episode patients and healthy subjects. Vermal subregion V3 was significantly smaller in multiple-episode bipolar disorder subjects than in healthy subjects. CONCLUSIONS: These results suggest that posterior-inferior cerebellar vermal abnormalities are present in patients with multiple-episode bipolar disorder.

Adult↗

Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task.

BACKGROUND: Bipolar disorder is characterized by disturbed mood homeostasis accompanied by cognitive impairments that appear to persist during euthymia. Cognitive probes, coupled with neuroimaging, provide an approach toward clarifying the neurophysiology of bipolar disorder. METHOD: Sixteen patients with euthymic bipolar disorder and 16 healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a counting Stroop interference task and a control condition. Task performance was correlated with regional brain activation differences between groups, and the effect on brain activation of receiving versus not receiving medications was evaluated. RESULTS: Bipolar patients exhibited impaired task performance relative to the healthy subjects. In addition, the two groups demonstrated significantly different patterns of brain activation during the interference task. Healthy subjects exhibited relatively increased activation in temporal cortical regions, middle frontal gyrus, putamen, and midline cerebellum. Bipolar subjects exhibited relatively greater activation in the medial occipital cortex. The groups demonstrated different associations between task performance and fMRI activation in these brain regions. No differences in activation in these regions were observed between patients who were versus those who were not receiving medications; however, patients receiving medications exhibited greater activation in the anterior cingulate and dorsolateral prefrontal cortex. CONCLUSIONS: These differences suggest that patients with euthymic bipolar disorder fail to activate brain regions associated with performance of an interference task, which may contribute to impaired task performance. Medications do not explain these differences but may influence activation of brain regions primarily associated with performing an interference task.

Adult↗

Parametric neurocognitive task design: a pilot study of sustained attention in adolescents with bipolar disorder.

BACKGROUND: Disruption in attention is one of the core features of bipolar disorder (BP). Therefore, neurocognitive paradigms assessing brain function in response to tasks of increasing attentional difficulty may be useful to clarify the neurophysiology of bipolar disorder. The aim of this study was to obtain pilot performance data using a parametric task of sustained attention that might be useful as an experimental paradigm for future functional neuroimaging studies. We hypothesized that task performance would worsen as task difficulty increased in manic and euthymic bipolar and healthy subjects. Additionally, we hypothesized that the groups would exhibit a similar decline in task performance as level of task difficulty increased and that within each level of task difficulty there would be similar performance among groups. METHODS: A novel parametric Continuous Performance Task-Identical Pairs (CPT-IP) version was administered to manic (N=10) and euthymic (N=10) adolescents with bipolar disorder and healthy controls (N=10). RESULTS: There were no statistically significant group differences in task performance as measured by discriminability, percent correct, false positive hits, and reaction time. However, within each group, performance on all measures worsened with increased attentional difficulty (p<0.0001). There were no statistically significant task difficulty by group interactions. Furthermore, medication exposure and comorbid attention-deficit hyperactivity disorder were not associated with most measures of task performance. However, BP subjects who were treated with medications had slower task performance compared with BP subjects who were unmedicated. LIMITATIONS: Larger studies examining the effects of specific medication classes on task performance are necessary. CONCLUSIONS: The results of this pilot study suggest that manic and euthymic BP patients do not exhibit attentional dysfunction as compared to healthy adolescents using a novel parametric version of the CPT-IP. Furthermore, our parametric CPT-IP version may be useful as a novel parametric neurocognitive paradigm for future functional neuroimaging studies of bipolar adolescents.

Adolescent↗

A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder.

The symptoms of bipolar disorder suggest dysfunction of anterior limbic networks that modulate emotional behavior and that reciprocally interact with dorsal attentional systems. Bipolar patients maintain a constant vulnerability to mood episodes even during euthymia, when symptoms are minimal. Consequently, we predicted that, compared with healthy subjects, bipolar patients would exhibit abnormal activation of regions of the anterior limbic network with corresponding abnormal activation of other cortical areas involved in attentional processing. In all, 10 unmedicated euthymic bipolar patients and 10 group-matched healthy subjects were studied with fMRI while performing the Continuous Performance Task-Identical Pairs version (CPT-IP). fMRI scans were obtained on a 3.0 T Bruker system using an echo planar imaging (EPI) pulse sequence, while subjects performed the CPT-IP and a control condition to contrast group differences in regional brain activation. The euthymic bipolar and healthy subjects performed similarly on the CPT-IP, yet showed significantly different patterns of brain activation. Specifically, bipolar patients exhibited increased activation of limbic, paralimbic, and ventrolateral prefrontal areas, as well as visual associational cortices. Healthy subjects exhibited relatively increased activation in fusiform gyrus and medial prefrontal cortex. In conclusion, these differences suggest that bipolar patients exhibit overactivation of anterior limbic areas with corresponding abnormal activation in visual associational cortical areas, permitting successful performance of an attentional task. Since the differences occurred in euthymia, they may represent trait, rather than state, abnormalities of brain function in bipolar disorder.

Adult↗