Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD)

Sachs, Gary S.; Thase, Michael E.; Otto, Michael W.; Bauer, Mark S.; Miklowitz, David J.; Wisniewski, Stephen R.; Lavori, Philip W.; Lebowitz, Barry D.; Rudorfer, Mathew; Frank, Ellen; Nierenberg, Andrew A.; Fava, Maurizio; Bowden, Charles L.; Ketter, Terence A.; Marangell, Lauren B.; Calabrese, Joseph R.; Kupfer, David J.; Rosenbaum, Jerrold F.

doi:10.1016/s0006-3223(03)00165-3

Cited by 491 publications

(432 citation statements)

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“…The Systematic Treatment Enhancement Program for Bipolar Disorder was a national, longitudinal cohort study designed to examine the effectiveness of treatments and their impact on the course of BP disorder 17 that enrolled 4361 participants across the United States who met the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for BPI, BPII, BP NOS, schizoaffective manic or BP type, or cyclothymic disorder on the basis of diagnostic interviews. Assessment of DSM-IV psychopathology was performed using two semistructured diagnostic interviews: (1) the Affective Disorders Evaluation, which includes mood and psychosis modules adapted from the Structured Clinical Interview for DSM-IV, 18 was administered by treating psychiatrists who were trained and certified in the administration of the interview and (2) the Mini International Neuropsychiatric Interview, 19 a validated structured diagnostic interview, was administered by trained clinical specialists.…”

Section: Step-bd Casesmentioning

confidence: 99%

Whole-genome association study of bipolar disorder

et al. 2008

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We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P = 1.66 Â 10 À7 ) and tetraspanin-8 (TSPAN8; P = 6.11 Â 10 À7 ). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P = 2.04 Â 10 À8 , TSPAN8; P = 7.57 Â 10 À7 and EGFR; P = 8.36 Â 10 À8 ). For replication, we genotyped 304 SNPs in family-based NIMH samples (n = 409 trios) and University of Edinburgh case-control samples (n = 365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

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Section: Step-bd Casesmentioning

confidence: 99%

Whole-genome association study of bipolar disorder

et al. 2008

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“…9 Briefly, the clinical diagnosis of bipolar disorder was established according to the structured interview the Affective Disorder Evaluation (ADE), which has previously been employed in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) project. 10 To minimize interrater variability, a best-estimate diagnosis was achieved by presenting the collected information at a diagnostic case conference where a consensus panel of experienced boardcertified psychiatrists specialized in bipolar disorder made the final diagnostic decision.Cerebrospinal fluid sampling was performed when the participants were in a stable euthymic mood, as judged by a physician. For ethical reasons, patients continued to take their prescribed medications.…”

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confidence: 99%

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Söderlund

Olsson

Samuelsson

et al. 2011

J Psychiatry Neurosci

168

121

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Background:In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention.Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its pathophysiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed. Methods: We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar dis order type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system. Results: The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respect ively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10). Limitations: All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out. Conclusion: Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder. In recent years, a role of the immune system in the pathogenesis of psychiatric diseases has gained increased attention. In this regard, many investigators have focused on cytokines, proteins that directly initiate and control immunological responses. We recently demonstrated a selective activation of brain interleukin (IL)-1β in schizophrenia, 2 a disease that appears similar to bipolar disorder with regard to symptomatology, treatment and risk genes. 3,4 Interestingly, a polymorphism in the promoter region of the IL1B gene has been suggested to comprise a shared genetic susceptibility for bipolar disorder and schizophrenia. 5 Indeed, bipolar disorder appears to be linked to inflammation, as indicated by genetic polymorphisms, gene expression and cytokine activation, 6 although direct evidence for a pathophysiological involvement of the immune system of the brain is still sparse. This may be 115 related to the fact that evaluation of cytokine levels in patients with bipolar disorder has been restricted to serum analyses. The bidirectional communication between the immune system of the brain and that of peripheral organs is complex, 7 and serum cytokines do not predict brain cytokine activation in healthy volunteers. 8 Hence, the immune system of the brain, including local cytokine release from microglia and astrocytes, may be independent of the immune sys...

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“…Participants were enrolled in STEP-BD, a prospective naturalistic study conducted between November 1999 and November 2004 (13). STEP-BD had a total of 22 U.S. participating sites, 13 of which accounted for over 90% of the enrolled participants (14).…”

Section: Methodsmentioning

confidence: 99%

“…After procedures were fully explained, written informed consent was obtained from all participants. STEP-BD methods are described in more detail elsewhere (13,14). …”

Section: Methodsmentioning

confidence: 99%

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One-Year Treatment Outcomes of African-American and Hispanic Patients With Bipolar I or II Disorder in STEP-BD

Gonzalez¹,

Bowden²,

Berman³

et al. 2010

Psychiatric Services

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Objective Few studies have compared treatment outcomes of African-American, Hispanic, and non-Hispanic white patients with bipolar disorder. The U.S. Systematic Treatment Enhancement Program for Bipolar Disorder compared one-year outcomes for bipolar I or II disorder from each of these racial-ethnic groups. Methods African Americans (N=155) were retrospectively compared with a matched group of non-Hispanic whites (N=729), and Hispanics (N=152) were compared with a separate matched group of non-Hispanic whites (N=822). Response and recovery outcomes were examined. Survival analysis was used to compare time to treatment response for depression (Montgomery-Asberg Depression Rating Scale) and mania (Young Mania Rating Scale) as well as global assessment of functioning (Global Assessment of Functioning). Results For manic and depressive symptoms, time to response and proportion of responders were similar across groups. Over the study year the proportion of days well was similar across groups. A smaller proportion of African Americans met criteria for improved global functioning. Depression response among African Americans with psychotic symptoms was slower than the response among African Americans without psychotic symptoms and among non-Hispanic whites with or without psychotic symptoms. No differences between Hispanics and non-Hispanic whites in response times and recovery were observed. Conclusions Results are consistent with U.S. clinical trials for other psychiatric disorders, which have reported similar outcomes for ratings of primary symptoms. Baseline psychotic symptoms are likely a significant contributor when African Americans with bipolar disorder are slow to recover. These results may be less generalizable to uninsured patients.

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Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD)

Cited by 491 publications

References 42 publications

Whole-genome association study of bipolar disorder

Whole-genome association study of bipolar disorder

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

One-Year Treatment Outcomes of African-American and Hispanic Patients With Bipolar I or II Disorder in STEP-BD

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