Biomedical subjects

Stephen M Strakowski

Publications and source records attributed to Stephen M Strakowski.

70 records · Page 4Linked to original sources

PubMed2003

The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence.

OBJECTIVE: Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania. METHOD: Bipolar disorder patients (N=166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score </=5 and Hamilton Depression Rating Scale score </=8), and functional (regaining of premorbid occupational and residential status). Rates of remission (syndromal recovery sustained >/=8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed. RESULTS: By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse. CONCLUSIONS: Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors.

Adolescent↗

PubMed2003

Atypical antipsychotics in the treatment of bipolar disorder.

Atypical antipsychotic medications are widely used for the treatment of bipolar disorder. Most empirical support suggests that these medications are efficacious in the treatment of acute mania, but there is considerably less support for the utility of these drugs in other phases of bipolar disorder. However, it is likely that several of these drugs will demonstrate efficacy in relapse prevention, and perhaps antidepressant efficacy in bipolar disorder as more studies are conducted. Atypical antipsychotics offer different side effect profiles than older antipsychotics, which may be of benefit for some patients. Consequently, atypical antipsychotics provide an important treatment option for bipolar patients.

Anticonvulsants↗

PubMed2003

Ethnicity and diagnosis in patients with affective disorders.

BACKGROUND: Clinically, African American psychiatric patients are disproportionately diagnosed with schizophrenia compared with white patients. Why this occurs is unknown. Extending prior work, the authors hypothesized that first-rank symptoms distract clinicians so that they fail to identify affective disorders in African Americans. METHOD: 195 African American and white patients with at least 1 psychotic symptom (delusions, hallucinations, or prominent thought disorder) at admission were recruited from January 1, 1998, through May 31, 2001. Each patient received 3 independent DSM-IV diagnoses: a clinical diagnosis, a structured-interview diagnosis, and an expert-consensus diagnosis. The expert-consensus diagnoses were derived from the structured interviews, which were audiotaped and transcribed, and medical records. After reviewing edited transcripts and medical records from which ethnic cues had been eliminated, 2 psychiatrists assigned expert-consensus diagnoses and first-rank symptom ratings. For the 79 patients who received an expert-consensus diagnosis of an affective disorder, clinical variables, diagnoses, and first-rank symptoms were compared between African American (N = 39) and white (N = 40) patients. RESULTS: Seventy-nine (41%) of 195 patients were diagnosed with an affective disorder by expert consensus. African American men with an expert-consensus affective disorder were significantly (p <.03) more likely than other patients to be diagnosed with a schizophrenia spectrum disorder by clinical assessment and structured interview. Although first-rank symptoms were more commonly identified in African American men, this finding did not explain the difference in diagnoses. Post hoc analyses suggested that African American men diagnosed with a schizophrenia spectrum disorder were more likely than other patients to have been identified during structured interview as having psychotic symptoms in the absence of affective symptoms. CONCLUSION: The apparent misdiagnosis of schizophrenia in African-Americans with mood disorders cannot be ascribed to differences in first-rank symptoms. However, it may be due to a perception that psychotic symptoms are more chronic or persistent than affective symptoms in these patients.

Adult↗

PubMed2002

Regional prefrontal gray and white matter abnormalities in bipolar disorder.

BACKGROUND: Previous magnetic resonance imaging (MRI) studies indicate that compared with healthy volunteers, patients with bipolar disorder have structural and functional abnormalities in the prefrontal cortex. The aim of this study was to investigate differences in prefrontal subregions between bipolar patients and healthy subjects. METHODS: Bipolar patients hospitalized for a manic episode (n = 17), and demographically matched healthy volunteers (n = 12) were recruited. Contiguous 1-mm coronal T1-weighted MRI slices were obtained using a Picker 1.5 Tesla scanner. The gray and white matter volumes of five prefrontal subregions of interest were measured: superior, middle, inferior, cingulate, and orbital. RESULTS: Bipolar patients had smaller left prefrontal gray matter volumes, specifically in the middle and superior subregions and smaller right prefrontal gray matter volumes, specifically in the inferior and middle subregions. White matter differences were not observed in any of the prefrontal subregions. CONCLUSIONS: The results suggest that bipolar patients have subregion-specific gray matter volume reductions in the prefrontal cortex as compared to healthy subjects. Further investigations into the role of specific prefrontal subregions in bipolar disorder are warranted.

Adolescent↗

PubMed2002

Neuroanatomic characterization of schizoaffective disorder using MRI: a pilot study.

For over 50 years, there has been uncertainty in the conceptual understanding and neuropathogenesis of the diagnosis of schizoaffective disorder (SCA). In order to better characterize SCA, we performed a quantitative assessment of MRI neuroanatomical structures in patients with SCA (n = 12), compared to patients with bipolar disorder (BPD) (n = 12) and healthy volunteers (HV) (n = 12). Patients diagnosed with SCA exhibited regional abnormalities on the striatum that resemble those seen in BPD. This study suggests that SCA has some neuroanatomical characteristics similar to BPD.

Adult↗

PubMed2002

Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment.

BACKGROUND: Childhood bipolarity (BP) and ADHD frequently co-occur, these children often receive stimulants. METHOD: We retrospectively evaluated 80 adolescents hospitalized with BP, manic or mixed, assessed severity of hospital course, and compared groups according to current/past stimulant or antidepressant treatment. RESULTS: Lifetime ADHD rate was 49%; 35% of patients had exposure to stimulants and 44% to antidepressants. Stimulant-exposed patients were younger than non-exposed (mean+/-S.D.=13.7+/-2 vs. 15.1+/-2 years, Z=-3.1, P=0.002). Only stimulant exposure was associated with worse hospitalization course (MANCOVA, Wilks' Lambda=0.87, F=3.4; df=70; P=0.02). CONCLUSION: Stimulant-exposed BP-adolescents may have more severe illness course not fully explained by ADHD comorbidity. LIMITATIONS: Retrospective methodology and lack of structured interviewing make it difficult to quantify exposure to stimulants and antidepressants.

Adolescent↗

PubMed2002

Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder?

The authors reviewed magnetic resonance imaging volumetric imaging results in major mood disorders, particularly comparing similarities and differences from studies of bipolar disorder and unipolar major depression. Abnormalities of cerebral brain regions appear inconsistently in mood disorders and, when present, typically consist of decreased frontal or prefrontal cortical volumes in both unipolar depression and bipolar disorder. In contrast, subcortical and medial temporal abnormalities are more commonly observed and are different between these two major classes of affective illness. Specifically, whereas structural enlargement of the basal ganglia and amygdala have been observed in bipolar disorder, in unipolar depression, these structures appear to be smaller in patients than healthy subjects. These findings suggest that affective illnesses may share in common an underdeveloped or atrophied prefrontal region, leading to loss of cortical modulation of limbic emotional networks. The effect of this loss results in unipolar depression or cycling (mania with depression) depending on the abnormalities of the subcortical structures involved. The cerebellum may also play a role in the presentation of mood disorders. This hypothesis remains speculative as much more research is needed to specifically examine how morphometric brain abnormalities translate into the neurophysiologic deficits that produce mood disorders.

Bipolar Disorder↗

PubMed2002

Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy.

OBJECTIVES: Proton magnetic resonance spectroscopy (MRS) provides insight into neurochemical processes. Imaging and postmortem studies have implicated abnormalities of structure and function within the frontal lobe. Patients with bipolar disorder having a manic or mixed episode were hypothesized to demonstrate metabolic abnormalities within the frontal lobe. METHODS: Seventeen patients with bipolar disorder type I (ages 16-35 years, mean 22 +/- 7.3 years) hospitalized for a manic (n = 9) or mixed (n = 8) episode and 21 healthy subjects (ages 16-35 years, mean 21.7 +/- 5.2 years) were evaluated with proton MRS. The gray matter medially and white matter laterally within the frontal lobe were sampled. Metabolite concentrations were calculated for each voxel, corrected for cerebral spinal fluid (CSF) contributions to the voxel, and compared between study populations. RESULTS: Patients demonstrated with multivariate analyses of variance (MANOVA) a significant overall difference in gray matter metabolite concentrations compared with healthy subjects. The largest effect sizes for group differences were found with reductions of N-acetyl aspartate (NAA) and Choline (Cho) concentrations (f = 0.41 and 0.37, respectively). A significant group difference with MANOVA in white matter metabolite concentrations was also observed with the largest effect size at f = 0.44 for elevation of the composite amino acid (AA) concentration. CONCLUSIONS: A reduction of NAA within the gray matter of patients suggests neuronal dysfunction. Altered phospholipid metabolism suggestive of a trend toward decreased volume is implicated with a reduction of Cho concentrations. Within white matter, composite concentrations of AAs were elevated in patients indicating altered neurotransmission.

Adolescent↗

PubMed2002

Parental reports of executive dysfunction in adolescents with bipolar disorder.

Bipolar disorder (BPD) is a serious mental illness that affects children and adolescents at a rate similar to that seen in adults. Extremely little is known, however, about cognitive functioning in childhood and adolescent BPD. The present study represents an initial effort to examine executive functioning in adolescents with BPD who are in a manic or mixed mood state, by collecting data from caregivers about the participants' performance on everyday tasks thought to be mediated by executive functioning abilities, using the Behavior Rating Inventory of Executive Function. In comparison to healthy volunteers, adolescents with BPD exhibited significant elevations across all of the measured functional domains. These elevations were evident even in adolescents with BPD who did not have comorbid ADHD, although they were most prominent in those with comorbidity. The findings suggest that adolescents with BPD have functional deficits on tasks requiring executive functioning skills that are not explicable solely on the basis of comorbid ADHD.

Adolescent↗

PubMed2002

Academic and cognitive abilities in children of parents with bipolar disorder: a test of the nonverbal learning disability model.

It has been hypothesized that children who are at genetic risk to develop bipolar disorder demonstrate deficiencies consistent with the syndrome of nonverbal learning disabilities (NLD); however, this hypothesis has never been tested directly. In the present study, a group of at-risk children (AR group; N = 28) was compared to a demographically matched control group of children of healthy parents (HC group; N = 24) for evidence of a constellation of features associated with NLD. Some characteristic features of NLD were evident, including significant Verbal IQ (VIQ) > Performance IQ (PIQ) discrepancies and psychomotor deficits. However, academic deficiencies in mechanical arithmetic relative to reading and spelling abilities were not demonstrated. These findings replicate and extend the current literature on the cognitive functioning of children of parents with Bipolar disorder (BPD). The results, however, do not support the presence of NLD in these children.

Bipolar Disorder↗

PubMed2002

Adjunctive topiramate treatment for pediatric bipolar disorder: a retrospective chart review.

OBJECTIVE: The objective of this study was to evaluate the effectiveness, safety, and tolerability of the anticonvulsant agent, topiramate, as adjunctive treatment for children and adolescents with bipolar disorders. METHODS: The outpatient medical charts of children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of bipolar disorder, type I or II, and who were treated with topiramate were retrospectively reviewed by two child and adolescent psychiatrists using the Clinical Global Impression (CGI) scale and the Clinical Global Assessment Scale (CGAS). Separate CGI ratings were made for mania and overall bipolar illness. RESULTS: Twenty-six patients (mean age 14 +/- 3.5 years) with bipolar disorder, type I (n = 23) or II (n = 3), who had been treated (mean duration 4.1 +/- 6.1 months) with topiramate (mean dose 104 +/- 77 mg/day) were identified. Response rate (defined by a CGI-Improvement score of < or = 2 at endpoint) was 73% for mania and 62% for overall illness. CGAS scores significantly improved from baseline to endpoint. No serious adverse events were reported. CONCLUSIONS: Although controlled trials are necessary, this retrospective study suggests that topiramate is effective and well tolerated as an adjunctive treatment for children and adolescents with bipolar disorder.

Adolescent↗

PubMed2002

A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania.

OBJECTIVES: This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated. METHOD: Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly. RESULTS: The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group. CONCLUSIONS: The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.

Acute Disease↗

PubMed2002

The effect of multiple doses of cimetidine on the steady-state pharmacokinetics of quetiapine in men with selected psychotic disorders.

Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders.

Adult↗

PubMed2002

Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder.

OBJECTIVE: Ventriculomegaly has been reported in bipolar disorder, although whether it occurs at illness onset or progresses during the course of the disorder is unknown. In addition, it is unknown whether ventriculomegaly in bipolar disorder reflects acquired volume loss or underdevelopment of periventricular structures. METHOD: Magnetic resonance imaging was used to measure the volumes of the lateral and third ventricles and periventricular structures (caudate, putamen, thalamus, hippocampus). Patients with DSM-IV bipolar disorder, 18 who were having a first episode and 17 with multiple episodes, were compared with 32 healthy subjects. RESULTS: The lateral ventricles were significantly larger in the patients with multiple-episode bipolar disorder than in the first-episode patients or the healthy subjects, even after periventricular and total cerebral volumes were taken into account. Having larger lateral ventricles was associated with a higher number of prior manic episodes. The multiple-episode patients had a smaller total cerebral volume than the healthy subjects but not the first-episode patients. The putamen was significantly larger in the first-episode patients (and nearly so in the multiple-episode patients) than in the healthy subjects, although there was no difference between patient groups. CONCLUSIONS: Lateral ventriculomegaly was greater in bipolar disorder patients who had had repeated manic episodes, but it does not appear to be secondary to small critical periventricular structures. A larger than normal striatum, which has been reported in previous studies, was observed in first-episode patients. These results support the importance of prospectively studying neuroanatomic changes in bipolar disorder.

Adolescent↗

PubMed2002

Differential prescription of maintenance antipsychotics to African American and white patients with new-onset bipolar disorder.

BACKGROUND: Antipsychotic medications are commonly prescribed as maintenance pharmacotherapy for patients with bipolar disorder. However, double-blind, placebo-controlled studies have yet to demonstrate a significant prophylactic effect of maintenance antipsychotic use in bipolar disorder, and long-term use of antipsychotics may place the patient at risk for neuroleptic-induced tardive dyskinesia. African American patients may be at increased risk because excess antipsychotic prescription appears to be common in this population, although this issue has not been longitudinally studied in bipolar disorder. METHOD: Fifty-eight patients meeting DSM-IV criteria for bipolar I disorder, with manic or mixed episode, were recruited at the time they were admitted for a first psychiatric hospitalization and then received longitudinal follow-up for up to 2 years. Comparisons were made between African American (N = 24) and white (N = 34) patients in medications prescribed and medication compliance after controlling for differences in clinical course. RESULTS: The African American and white patient groups were similar demographically. After controlling for differences in clinical course, African Americans, compared with white patients, (1) received antipsychotics for a significantly greater percentage of follow-up time (F = 7.9, df = 1.52; p < .007), (2) were more likely to receive antipsychotics during periods without psychotic symptoms, and (3) were significantly more likely to receive conventional antipsychotics (chi 2 = 4.0, df = 1, p < .05). African Americans also demonstrated poorer treatment adherence, although that finding did not explain the differences in antipsychotic prescription. CONCLUSION: Even when demographically similar to white patients, African Americans with bipolar disorder may be more likely to receive maintenance antipsychotic treatment. The specific reasons for this finding are not clear, suggesting that studies are warranted that examine clinicians' rationale for differentially prescribing antipsychotics for African American and white patients during the early course of bipolar disorder.

Adolescent↗

PubMed2002

A reevaluation of sustained attention performance in temporal lobe epilepsy.

Reports of normal Continuous Performance Test (CPT) accuracy in patients with temporal lobe epilepsy (TLE) stand in contrast to a demonstration of nonspecific absolute reaction time (RT) deficits in this population. In this study, we examined CPT data from a TLE sample for potential RT deficits across three consecutive blocks of time during the vigil. Seventeen patients with medically intractable epilepsy of temporal lobe origin and 17 healthy volunteers participated. The Conners CPT was used to assess sustained attention over a 14-min vigil. There were no significant group differences in accuracy. There was, however, a significant interaction between groups and time intervals, with disproportionate RT increases for patients at the end of the vigil. These findings are consistent with a report of nonspecific RT deficits in TLE despite normal accuracy scores, and further indicate impaired RT performance over time.

Journal Article↗