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Stephen M Strakowski

Publications and source records attributed to Stephen M Strakowski.

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↗

Child behavior checklist profiles of children and adolescents with and at high risk for developing bipolar disorder.

In order to recognize behavioral patterns in children and adolescents at risk for developing bipolar disorder, this study examined Child Behavior Checklist (CBCL) profiles of bipolar offspring both with (BD group) and without ("at-risk" or AR group) bipolar disorder themselves. The BD youth had three CBCL subscale T scores > or = 70 (attention problems, delinquent behavior, and aggression) and scored significantly higher than healthy comparison youth on all CBCL subscales. AR youth did not have any T scores > or = 70; however, they scored higher than healthy comparisons in the anxiety/depression, attention problems, aggression, and withdrawal subscales. AR and BD youth differed significantly on all scales except somatic complaints and anxiety/depression.

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↗

Obstetrical complications in children at high risk for bipolar disorder.

OBJECTIVE: To examine obstetrical complications as a risk factor for developing bipolar disorder (BPD). We hypothesized that children with a bipolar parent would be at greater risk for obstetrical complications than demographically matched children of healthy adults. Additionally, within this "at-risk" (AR) sample, we hypothesized that obstetrical complications would be associated with the development of psychiatric disorders. METHODS: The Washington University in St. Louis Kiddie-Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS) was administered to children (AR) who had at least one parent with BPD (N=36) and children of healthy parents (HC) (N=27), by raters who were blind to diagnostic category. To assess obstetrical risk history, the Rochester Research Obstetrical Scale (ROS) was administered to parents of AR and HC children. RESULTS: Children at familial risk for BPD had greater total (p=0.02) and prenatal (p=0.006) obstetrical complication scores than children of healthy parents. However, obstetrical complications were not associated with the development of affective, anxiety, or disruptive behavioral disorders within the at-risk group. CONCLUSION: Our data suggest that compared with children of families without BPD, children of parents with BPD may be at greater risk for obstetrical complications, particularly those that occur during the prenatal period; however, at this early follow-up period factors other than obstetrical complications appear to contribute to the differences in rates of psychiatric disorders between these groups.

Adolescent↗

Fast spectroscopic imaging using online optimal sparse k-space acquisition and projections onto convex sets reconstruction.

Long acquisition times, low resolution, and voxel contamination are major difficulties in the application of magnetic resonance spectroscopic imaging (MRSI). To overcome these difficulties, an online-optimized acquisition of k-space, termed sequential forward array selection (SFAS), was developed to reduce acquisition time without sacrificing spatial resolution. A 2D proton MRSI region of interest (ROI) was defined from a scout image and used to create a region of support (ROS) image. The ROS was then used to optimize and obtain a subset of k-space (i.e., a subset of nonuniform phase encodings) and hence reduce the acquisition time for MRSI. Reconstruction and processing software was developed in-house to process and reconstruct MRSI using the projections onto convex sets method. Phantom and in vivo studies showed that good-quality MRS images are obtainable with an approximately 80% reduction of data acquisition time. The reduction of the acquisition time depends on the area ratio of ROS to FOV (i.e., the smaller the ratio, the greater the time reduction). It is also possible to obtain higher-resolution MRS images within a reasonable time using this approach. MRSI with a resolution of 64 x 64 is possible with the acquisition time of the same as 24 x 24 using the traditional full k-space method.

Algorithms↗

Cortical reorganization following modified constraint-induced movement therapy: a study of 4 patients with chronic stroke.

OBJECTIVE: To determine whether cortical changes occur following participation in a program of modified constraint-induced movement therapy (mCIMT). DESIGN: Pre-post, case series. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Two men and 2 women with unilateral stroke occurring more than 1 year prior to study entry and moderate stable motor deficits. INTERVENTION: Subjects participated in mCIMT, comprised of structured, 30-minute therapy sessions emphasizing affected arm use in valued activities, which occurred 3 days a week for 10 weeks. Their unaffected arms were restrained 5 days a week for 5 hours. MAIN OUTCOME MEASURES: The Action Research Arm Test (ARAT), upper-extremity portion of the Fugl-Meyer Assessment (FMA), Motor Activity Log (MAL), and functional magnetic resonance imaging (fMRI) at 4T were administered before and after mCIMT. RESULTS: Three subjects exhibited score increases on the MAL, ARAT, and FMA, representing increased affected arm use, impairment, and function. These subjects reported new ability to perform valued activities with the affected hand, such as writing. These subjects also displayed cortical reorganization on fMRI. One subject exhibited minimal affected arm use changes, modest function changes, and no cortical fMRI changes. CONCLUSIONS: Increased affected arm use during mCIMT appears to induce cortical reorganization, as measured by fMRI. In patients who responded to mCIMT, cortical reorganization was positively related to degree of increase in affected arm use and ability. Because mCIMT is more easily administered than longer duration protocols, mCIMT may be a more practicable way of studying plasticity.

Adult↗

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↗

Preliminary study of relationships among measures of depressive symptoms in adolescents with bipolar disorder.

PURPOSE: The aim of this study was to explore relationships between the Children's Depression Rating Scale-Revised (CDRS-R) and Hamilton Rating Scale for Depression (HAM-D) in adolescent bipolar disorder. We hypothesized that CDRS-R and HAM-D scores would be significantly correlated and both scales would be sensitive to change resulting from treatment. METHODS: Data from a randomized, double-blind, placebo-controlled study of quetiapine with divalproex versus divalproex alone (n = 30) and an open-label study of lithium (n = 27) were used. Assessments using the CDRS-R and HAM-D were completed separately without any dependence on ratings from the alternate rating scale or specific order. All raters for symptom rating scales were blinded to the study for which they were completing a patient assessment and the intent to conduct these post hoc analyses and were different from those who performed diagnostic interviews. Relationships between these measures were assessed using the Pearson correlation coefficient, and receiver operator characteristic curves evaluated the ability of CDRS-R and HAM-D scores to predict the level of global improvement. RESULTS: The mean (+/- standard deviation) age of subjects was 15.0 +/- 1.6 years. Baseline CDRS-R and HAM-D scores were moderately correlated (r = 0.63; p < 0.001), while week 6 scores showed stronger correlation (r = 0.88; p < 0.001). Both measures showed significant main effects for time on treatment (CDRS-R: F(3.4,191.2) = 39.4, p < 0.001; HAM-D: F(3.9,217.9) = 38.5, p < 0.001). A CDRS-R score of 30.5 and HAM-D score of 7.5 represent the highest sensitivity and specificity in classifying responders and nonresponders. A 42.2% and 60.6% reduction in baseline CDRS-R and HAM-D scores, respectively, provided the highest sensitivity and specificity. CONCLUSIONS: Our preliminary results demonstrated that CDRS-R and HAM-D scores were significantly correlated, suggesting that either measure may be used to assess depressive symptoms in studies of adolescent bipolar disorder. Limitations to this study included a relatively small pooled sample, variation in clinician judgment, and study design not specific for the comparison of rating scales. Studies with methods specific to evaluate and compare these rating scales and larger patient samples from multiple treatment sites are needed to confirm these findings.

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↗

Stability of estimated IQ across mood state in patients with bipolar disorder.

OBJECTIVES: The goal of this study was to assess the impact of mania symptoms on the stability of the American version of the National Adult Reading Test (ANART), a measure that provides a putative estimate of premorbid intellectual functioning. METHODS: The ANART was administered to a sample of 10 inpatients with bipolar disorder who were experiencing an acute episode of mania. During a subsequent follow-up visit during which these individuals exhibited at most minimal mood symptoms, the ANART was re-administered. RESULTS: ANART estimated intelligence quotient (IQ) scores during mania and affective stability were assessed in the 10 patients using a paired sample t-test. Within-subject performance across the two mood states did not significantly differ [t(9) = -1.24, p = 0.25]. Additionally, the greatest individual difference across mood states was only 3.68 points, and the average estimated IQ difference across mood states was 1.66. CONCLUSIONS: While the results are preliminary and based on a small sample, the highly consistent scores achieved across mood states in this study suggest that the ANART is a reliable indicator of premorbid IQ.

Acute Disease↗

Phenomenology associated with age at onset in patients with bipolar disorder at their first psychiatric hospitalization.

OBJECTIVE: To compare the clinical presentation of patients with early-onset (age <18 years) and typical-onset (age 20-30 years) bipolar disorder at the time of first hospitalization. METHODS: Patients, aged 12-45 years at their first psychiatric hospitalization, with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were evaluated on measures of manic, depressive, and positive psychotic symptoms. Differences in symptom profiles between early- and typical-onset groups were examined. RESULTS: One hundred three early-onset and 58 typical-onset patients were compared. Mixed episodes were more common in the early-onset group, while psychotic features and current substance use were more common in the typical-onset group. There was no significant difference in manic symptom severity ratings between early- and typical-onset groups (F = 1.8, df = 11, 144, p = 0.06). However, these groups differed in depressive (F = 4.2, df = 16, 139, p < 0.001) and positive psychotic (F = 2.8, df = 16, 139, p = 0.001) symptom profiles. Typical-onset bipolar patients reported more severe weight loss and formal thought disorder compared with early-onset patients. CONCLUSIONS: Depressive and positive psychotic symptoms may differ in association with age at onset among patients with bipolar disorder. Additional studies are necessary to determine whether homogeneous phenotypes of bipolar disorder can be delineated based upon age at onset.

Adolescent↗

Ethnic differences in symptom presentation of youths with bipolar disorder.

OBJECTIVE: To compare symptom profiles of African-American and white adolescents with a diagnosis of bipolar disorder. METHOD: Adolescents, aged 12-18 years at their first psychiatric hospitalization, with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were evaluated on measures of manic, depressive, and positive symptoms of psychosis. Ethnic differences in symptom profiles were examined using multivariate analysis of covariance, and specific symptoms contributing to the difference were analyzed. RESULTS: Ethnic differences existed in manic and positive symptom profiles, but not depressive symptoms. Compared with the white cohort, African-American youths were diagnosed more frequently as having psychotic features, and had higher ratings for auditory hallucinations. CONCLUSIONS: Similar to adults, symptom expression in adolescent bipolar disorder may differ between ethnic groups. Future studies are needed to replicate these findings and explore possible explanations.

Adolescent↗