Willem A. Nolen

The Stanley Foundation Bipolar Treatment Outcome Network: II. Demographics and illness characteristics of the first 261 patients

BACKGROUNDnSince recent NIMH Bipolar Disorder Workshops highlighted the dearth of longitudinal and controlled studies of bipolar illness, the Stanley Foundation Bipolar Network (SFBN) has recruited a large cohort of patients with bipolar disorder to begin to address these issues. This report describes the demographics and course of illness characteristics of this study population.nnnMETHODSnThe first 261 outpatients to be diagnosed by the Structured Clinical Interview for DSM-IV (SCID) and complete a detailed patient and a brief clinician questionnaire are described. All patients met DSM-IV criteria for bipolar I (n=211), bipolar II (n=42), or NOS (n=5) or schizoaffective (n=3), bipolar type. Chi-square and t-tests were used to examine statistically significant associations among important demographic and descriptive items.nnnRESULTSnThe general demographic and illness characteristics were similar to those in many bipolar clinical samples and not dissimilar from those reported in epidemiological surveys. The majority of patients had been hospitalized, with almost half reporting a worsening of illness over time, and two-thirds were not asymptomatic between episodes. First treatment for patients had been delayed by an average of 10 years from illness onset (by SCID). Almost a third of patients had attempted suicide at least once, and 30% reported current suicidal ideation at study entry. A total of 62% reported moderate to severe impact of the illness on occupational functioning. Early onset bipolar illness (< or =17 years old) was associated with increased frequency of mood switches, worsening course of illness, and history of early abuse (physical, verbal, or sexual).nnnCONCLUSIONnThe SFBN represents a sample of predominantly BP I patients largely recruited from the community who will be followed in detail longitudinally, participate in clinical trials, and thus help advance our understanding and treatment of this life-threatening medical disorder. While there is a broad range of illness characteristics and severity, the majority of patients have been severely impacted by their illness despite the availability of multiple conventional treatment approaches in the community. These data further underscore the need for development of new and earlier treatment interventions.nnnLIMITATIONnThe SFBN population is limited by the lack of random selection and represents a cohort willing to be treated and followed intensively in academic tertiary referral centers. While its characteristics are similar to many clinical study populations, the generalizability to non-clinic populations remains uncertain.

Early physical and sexual abuse associated with an adverse course of bipolar illness

BACKGROUNDnThere is growing awareness of the association between physical and sexual abuse and subsequent development of psychopathology, but little is known, however, about their relationship to the longitudinal course of bipolar disorder.nnnMETHODSnWe evaluated 631 outpatients with bipolar I or II disorder for general demographics, a history of physical or sexual abuse as a child or adolescent, course of illness variables, and prior suicide attempts, as well as SCID-derived Axis I and patient endorsed Axis II comorbidity.nnnRESULTSnThose who endorsed a history of child or adolescent physical or sexual abuse, compared with those who did not, had a history of an earlier onset of bipolar illness, an increased number of Axis I, II, and III comorbid disorders, including drug and alcohol abuse, faster cycling frequencies, a higher rate of suicide attempts, and more psychosocial stressors occurring before the first and most recent affective episode. The retrospectively reported associations of early abuse with a more severe course of illness were validated prospectively.nnnCONCLUSIONSnGreater appreciation of the association of early traumatic experiences and an adverse course of bipolar illness should lead to preventive and early intervention approaches that may lessen the associated risk of a poor outcome.

High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure

BACKGROUNDnWe assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and thyroid failure in outpatients with bipolar disorder compared with two control groups.nnnMETHODSnThe TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226), a population control group (n = 252), and psychiatric inpatients of any diagnosis (n = 3190) were measured. Thyroid failure was defined as a raised thyroid stimulating hormone level, previously diagnosed hypothyroidism, or both. Subjects were compared with attention to age, gender, and exposure to lithium.nnnRESULTSnThe TPO-Abs were more prevalent in bipolar patients (28%) than population and psychiatric controls (3-18%). The presence of TPO-Abs in bipolar patients was associated with thyroid failure, but not with age, gender, mood state, rapid cycling, or lithium exposure. Thyroid failure was present in 17% of bipolar patients and more prevalent in women. It was associated with lithium exposure, especially in the presence of TPO-Abs, but not with current rapid cycling, although an association may have been masked by thyroid hormone replacement.nnnCONCLUSIONSnThyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment. These variables appear to be independent risk factors for the development of hypothyroidism, especially in women with bipolar disorder.

Prevalence of Psychopathology in Children of a Bipolar Parent

OBJECTIVEnTo determine psychopathology in adolescent children of a bipolar parent living in the Netherlands, using multiple sources of information (self-, parent, and teacher reports).nnnMETHODnProblem behavior in 140 offspring (aged 12-21 years) of 86 bipolar parents was assessed with the Child Behavior Checklist (CBCL), the Teachers Report Form (TRF), and the Youth Self-Report (YSR) between 1997 and 1999. All adolescents, bipolar parents, and their available spouses were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL).nnnRESULTSnHigher problem scores were found for 8 of the 11 CBCL scales for girls and 4 of the 11 CBCL scales for boys, compared with a Dutch normative sample, and 1 Young Adult Self-Report (YASR) scale for girls compared with an American normative sample. Lower problem scores were found on 4 YSR and 4 YASR scales for boys, 1 TRF scale for girls, and 1 TRF scale for boys. The prevalence of current DSM-IV diagnoses in the offspring was 29% and of life-time DSM-IV diagnoses, 44%.nnnCONCLUSIONSnThe prevalence of problem behavior and DSM-IV diagnoses found in our sample did not support the notion that the level of psychopathology in children aged 12 to 21 years of bipolar parents is highly elevated. This study, similar to prior studies, suffers from lack of information on the representativeness of the sample and a rather low response rate.

Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM TM -p) for longitudinal assessment of bipolar illness

BACKGROUNDnSystematic and accurate depiction of a patients course of illness is crucial for assessing the efficacy of maintenance treatments for bipolar disorder. This need to rate the long-term prospective course of illness led to the development of the National Institute of Mental Health prospective Life Chart Methodology (NIMH-LCM-p or LCM). The NIMH-LCM-p allows for the daily assessment of mood and episode severity based on the degree of mood associated functional impairment. We have previously presented preliminary evidence of the reliability and validity of the LCM, and its utility in clinical trials. This study is a further and more extensive validation of the clinician rated NIMH-LCM-p.nnnMETHODSnSubjects included 270 bipolar patients from the five sites participating in the Stanley Foundation Bipolar Network. Daily prospective LCM ratings on the clinician form were initiated upon entry, in addition to at least monthly ratings with the Inventory of Depressive Symptomatology-clinician rated (IDS-C), the Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). We correlated appropriate measures and time domains of the LCM with the IDS-C, YMRS and GAF.nnnRESULTSnSeverity of depression on the LCM and on the IDS-C were highly correlated in 270 patients (r = -0.785, P < 0.001). Similarly, a strong correlation was found between LCM mania and the YMRS (r = 0.656, P < 0.001) and between the LCM average severity of illness and the GAF (r = -0.732, P < 0.001).nnnCONCLUSIONSnThese data further demonstrate the validity and potential utility of the NIMH-LCM-p for the detailed daily longitudinal assessment of manic and depressive severity and course, and response to treatment.

Prevalence of bipolar disorder in the general population: a Reappraisal Study of the Netherlands Mental Health Survey and Incidence Study

Objective:u2002 The Netherlands Mental Health Survey and Incidence Study (NEMESIS) is a Dutch population study using a fully structured interview (Composite International Diagnostic Interview, CIDI), administered by trained interviewers. Based on all three assessments of NEMESIS, 2.4% of the respondents were identified with lifetime bipolar disorder (DSM‐III‐R).

A high prevalence of organ-specific autoimmunity in patients with bipolar disorder

BACKGROUNDnIn a previous study, we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in patients with bipolar disorder. Here we report the prevalence of other organ-specific autoantibodies: H/K adenosine triphosphatase (ATPA), glutamic acid decarboxylase-65 (GAD65A), and GAD-67 (GAD67A).nnnMETHODSnATPA, GAD65A, and GAD67A were determined (via a commercially available enzyme linked immunosorbent assay for ATPA, and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder, in 74 patients with DSM-IV schizophrenia, and in 220 healthy control subjects.nnnRESULTSnThe positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients compared with those in healthy control subjects (11.7 vs. 6.1% and 11.3 vs. 2.6% respectively; p <.05). Schizophrenia patients did not show such statistically higher prevalence. The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium. Interestingly, the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder. The level of TPOA was negatively correlated with the serum level of sIL-2R, a measure of T cell activation.nnnCONCLUSIONnBipolar disorder is associated with organ-specific autoimmunity to the antigens TPO, H/K ATPase, and GAD65.

Earlier onset of bipolar disorder in children by antidepressants or stimulants? An hypothesis.

Among adults and adolescents, bipolar disorder (BD) has a similar prevalence in the US and in the Netherlands. However, among pre-pubertal children, BD is frequently diagnosed in the US and seldomly in the Netherlands. This suggests that, among children, the prevalence of BD is lower in the Netherlands than in the US, indicating an earlier onset of BD in the US than in the Netherlands. It is hypothesized that this may be related to the greater use of antidepressants and stimulants for depression or attention deficit disorder with hyperactivity by US children. In those children who are genetically at risk to develop BD, these drugs may lead to a switch into mania.

The Stanley Foundation Bipolar Network. 2. Preliminary summary of demographics, course of illness and response to novel treatments.

BACKGROUNDnThe Stanley Foundation Bipolar Network (SFBN) evaluates treatments, course and clinical and neurobiological markers of response in bipolar illness.nnnAIMSnTo give a preliminary summary of emerging findings in these areas.nnnMETHODnStudies with established and potentially antimanic, antidepressant and mood-stabilising agents range from open case series to double-blind randomised clinical trials, and use the same core assessment methodology, thereby optimising the comparability of the outcomes. The National Institute of Mental Health Life Chart Method is the core instrument for retrospective and prospective longitudinal illness description.nnnRESULTSnThe first groups of patients enrolled show a considerable degree of past and present symptomatology, psychiatric comorbidity and functional impairment. There are associations of both genetic and early environmental factors with more severe courses of illness. Open case series with add-on olanzapine, lamotrigine, gabapentin or topiramate show a differential spectrum of effectiveness in refractory patients.nnnCONCLUSIONSnThe SFBN provides important new data for the understanding and treatment of bipolar disorder.

The societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands

Objective:u2002 To assess the societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands.