Risk factors for major depression during midlife among a community sample of women with and without prior major depression: are they the same or different?

BACKGROUND: Women's vulnerability for a first lifetime-onset of major depressive disorder (MDD) during midlife is substantial. It is unclear whether risk factors differ for first lifetime-onset and recurrent MDD. Identifying these risk factors can provide more focused depression screening and earlier intervention. This study aims to evaluate whether lifetime psychiatric and health histories, personality traits, menopausal status and factors that vary over time, e.g. symptoms, are independent risk factors for first-onset or recurrent MDD across 13 annual follow-ups. METHOD: Four hundred and forty-three women, aged 42-52 years, enrolled in the Study of Women's Health Across the Nation in Pittsburgh and participated in the Mental Health Study. Psychiatric interviews obtained information on lifetime psychiatric disorders at baseline and on occurrences of MDD episodes annually. Psychosocial and health-related data were collected annually. Cox multivariable analyses were conducted separately for women with and without a MDD history at baseline. RESULTS: Women without lifetime MDD at baseline had a lower risk of developing MDD during midlife than those with a prior MDD history (28% v. 59%) and their risk profiles differed. Health conditions prior to baseline and during follow-ups perception of functioning (ps < 0.05) and vasomotor symptoms (VMS) (p = 0.08) were risk factors for first lifetime-onset MDD. Being peri- and post-menopausal, psychological symptoms and a prior anxiety disorder were predominant risk factors for MDD recurrence. CONCLUSIONS: The menopausal transition warrants attention as a period of vulnerability to MDD recurrence, while health factors and VMS should be considered important risk factors for first lifetime-onset of MDD during midlife.

Do anxiety symptoms predict major depressive disorder in midlife women? The Study of Women's Health Across the Nation (SWAN) Mental Health Study (MHS).

BACKGROUND: In women, anxiety symptoms are common and increase during midlife, but little is known about whether these symptoms predict onsets of major depressive disorder (MDD) episodes. We examined whether anxiety symptoms are associated with subsequent episodes of MDD in midlife African-American and Caucasian women, and whether they confer a different risk for first versus recurrent MDD episodes. METHOD: A longitudinal analysis was conducted using 12 years of data from the Study of Women's Health Across the Nation (SWAN) Mental Health Study (MHS). The baseline sample comprised 425 Caucasian (n=278) and African American (n=147) community-dwelling women, aged 46.1±2.5 years. Anxiety symptoms measured annually using a self-report questionnaire were examined in relation to MDD episodes in the subsequent year, assessed with the SCID. Multivariable models were estimated with random effects logistic regression. RESULTS: Higher anxiety symptoms scores were associated with a significantly higher adjusted odds of developing an episode of MDD at the subsequent annual visit [odds ratio (OR) 1.47, p=0.01], specifically for a recurrent episode (OR 1.49, p=0.03) but non-significant for a first episode (OR 1.32, p=0.27). There were no significant racial effects in the association between anxiety symptoms and subsequent MDD episodes. CONCLUSIONS: Anxiety symptoms often precede MDD and may increase the vulnerability of midlife women to depressive episodes, particularly recurrences. Women with anxiety symptoms should be monitored clinically during the ensuing year for the development of an MDD episode.

Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders. METHOD: Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women's Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually. RESULTS: Women were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study. CONCLUSIONS: The risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.

Factors Influencing Longitudinal Stair Climb Performance from Midlife to Early Late Life: The Study of Women's Health Across the Nation Chicago and Michigan Sites.

OBJECTIVES: To quantify the longitudinal change in stair climb performance (a measure indicative of both physical function and muscle power), determine whether physical activity is related to slower decline in performance, and to identify factors that modify the longitudinal change in performance among women from midlife to late life. DESIGN: Longitudinal cohort study with up to 15 study visits. SETTING: Two sites of the Study of Women's Health Across the Nation. PARTICIPANTS: Black (n=411) and white (N=419) women followed from median age 47.0 (44.6-49.6) to 62.0 (55.8-65.3) years. INTERVENTIONS: N/A. MEASUREMENTS: Performance on a stair climb test (ascend/descend 4 steps, 3 cycles) was timed. Physical activity (PA) was assessed using the Kaiser Physical Activity Survey (KPAS; possible range 0-15 points). Sociodemographic and health factors were assessed via self-report. BMI was calculated with measured height and weight. Mixed-effects regression modeled longitudinal change in stair climb performance. RESULTS: Average baseline stair climb time was 18.12 seconds (95% CI: 17.83-18.41), with 0.98% (95% CI: 0.84%-1.11%) annual slowing. In fully adjusted models, higher levels of PA were associated with faster stair climb times (2.09% faster per point higher, 95% CI: -2.87%- -1.30%), and black women had 5.22% (95% CI: 2.43%-8.01%) slower performance compared to white women. Smoking, financial strain, diabetes, osteoarthritis, fair/poor health, and stroke were associated with 3.36% (95% CI: 0.07%-6.65%), 7.56% (95% CI: 4.75%-10.37%), 8.40% (95% CI: 2.89%-13.92%), 8.46% (95% CI: 5.12%-11.79%), 9.16% (95% CI: 4.72%-13.60%), and 16.94% (95% CI: 5.37%-28.51%) slower performance, respectively. In separate models, higher BMI (per 1-unit), osteoarthritis, fair/poor health, and diabetes, were each associated with 0.06% (95% CI:0.04%-0.08%), 0.48% (95% CI:0.12%-0.84%), 0.81% (95% CI:0.35%-1.28%), and 0.84% (95% CI:0.22%-1.46%), additional slowing per year over time. CONCLUSION: Significant declines in function were evident as women transitioned from midlife to early late life. Declines were amplified by indicators of poor health, emphasizing the importance of health in midlife for promoting healthy aging.

REM latency and the recovery from depression: getting over divorce.

OBJECTIVE: The authors' goal was to address five questions: 1) What is the frequency of early REM sleep in subjects in the process of divorce who meet diagnostic criteria for major depressive disorder? 2) What is the frequency of this sign in subjects in the process of divorce who are not depressed? 3) How often does this sign persist following remission of depressive symptoms? 4) What is the predictive value of early REM sleep among depressed subjects for later adjustment to the process of divorce? and 5) What is the role of a family history of depression or alcoholism in the presence and persistence of early REM sleep? METHOD: Two hundred fourteen volunteers undergoing marital separation were recruited; 70 of these subjects were selected for a 3-night sleep study. Forty of the 70 subjects met criteria for depression and 30 did not; 61 (87%) returned for repeat studies 1 year later. RESULTS: Fifteen (38%) of the 40 depressed subjects had short REM latency. Seven of these continued to have short REM latency 1 year later, but none of these met the criteria for depression at that time. A higher proportion of these subjects had made a good adjustment to their new life than did depressed subjects whose initial and follow-up REM latencies fell within the normal range. CONCLUSIONS: These data suggest that depressed individuals with normal REM latency may need more aggressive treatment intervention.

Predicting the "revolving door" phenomenon among patients with schizophrenic, schizoaffective, and affective disorders.

OBJECTIVE: A subpopulation of chronically mentally ill patients, sometimes referred to as "revolving door" patients, are frequently readmitted to psychiatric units. This study examined the relationships among demographic features, diagnostic characteristics, and frequency of hospitalization of patients from four state hospitals. METHOD: Two semistructured, standardized instruments, the Schedule for Affective Disorders and Schizophrenia and a life events history, were administered to 135 inpatients who met the Research Diagnostic Criteria for schizophrenia (N = 56), schizoaffective disorder (N = 33), unipolar major depressive disorder (N = 23), and bipolar disorder (N = 23). Criminal history was assessed by arrest records. The main outcome measure was the number of hospitalizations. RESULTS: Chi-square and trend test analyses indicated that substance abuse and noncompliance with medication regimens were significantly associated with higher frequencies of hospitalization. A multiple regression model, which included alcohol/drug problems, medication noncompliance, and six sociodemographic and diagnostic variables (age, gender, race, marital status, years of education, and diagnosis) accounted for a significant proportion of the ability to predict frequency of hospitalization. Half of this predictability was due to the relationship of substance abuse and medication noncompliance with number of hospitalizations. CONCLUSIONS: Alcohol/drug problems and noncompliance with medication were the most important factors related to frequency of hospitalization. Preventing these behaviors through patient education may reduce rehospitalization rates.

Anxiety syndromes and their relationship to depressive illness.

The DSM-III categories of anxiety disorder are reviewed, and a study of anxiety symptoms in subjects with RDC-defined major depression is described. Anxiety appears to be common in major depression; 29% of the sample studied had a history of panic attacks, and moderate psychic anxiety was reported in 62%. Analysis by depressive subtypes showed no differences for the bipolar/unipolar distinction. However, significant differences in anxiety symptoms were seen in the primary vs. secondary and, more strikingly, endogenous vs. nonendogenous categories. The presence/severity of anxiety symptoms thus appears to be an important factor in the clinical management of major depression and may eventually serve as a guide to choosing among the increasing number of available antidepressant medications.

The long-term management of bipolar disorders with lithium, carbamazepine, and antidepressants.

Carbamazepine is gaining recognition as a valuable drug in the treatment of patients with bipolar disorders who fail to respond to lithium. Clinical experience in the treatment of 90 bipolar patients is described: 48% responded to lithium alone or in combination with other standard drug treatments. A subgroup of 34 lithium nonresponders were treated with carbamazepine; of these, 17 (50%) responded to carbamazepine and 5 responded to carbamazepine plus lithium, for a total response rate of 65%. Issues of side effects, blood levels, and compliance are discussed. These observations support the efficacy and safety of carbamazepine and suggest the need for well-controlled double-blind studies.

Alprazolam and depression: a review of risks and benefits.

Therapeutic efficacy for depression and panic disorder has been demonstrated with the triazolobenzodiazepine alprazolam. However, potentially serious adverse events, including depression and suicide attempts, have been reported in patients taking this medication. In this paper, reports addressing the association between each of these two events and benzodiazepine use in general and, more specifically, alprazolam use, are reviewed. We conclude that while these adverse events do occur in patients taking alprazolam, the causal relationship remains unclear and requires further study. Fortunately, these events are observed only rarely, so the prudent clinician may continue to safely prescribe this useful medication.

Suicide: a four-pathway clinical-biochemical model.

This chapter, based on a review of recent research as well as data presented in this report, proposes four hypothetical pathways leading to suicide in clinical depression: (1) an acute pathway involving severe anxiety/agitation associated with high brain corticotrophin-releasing factor (CRF or CRH) levels, (2) trait baseline and reactivity hopelessness, (3) severe anhedonia, and (4) trait impulsiveness associated with low brain serotonin turnover and low total cholesterol as a possible peripheral correlate. Clinical research showing evidence for acute versus chronic high-risk suicide factors and other studies linking severe anxiety/agitation to high CRF levels will be presented as associated with acute suicidal risk, which is potentially reversible with recognition and treatment. Evidence for anhedonia severity as a risk factor and trait, as well as evidence that baseline hopelessness and sensitivity are traits related to chronic suicide risk, will be presented. Finally, evidence relating low serum cholesterol to suicide in depressed inpatients will be presented in the context of literature suggesting a relationship between low serum cholesterol and violent death and suicide in population studies. Data suggesting a relationship between low serum cholesterol and decreased CSF 5-HIAA, suggesting reduced serotonin turnover, will be presented, in light of prior studies relating low CSF 5-HIAA and violent suicide. These data taken together suggest four pathways to suicide that are worth investigating in order to better understand the mechanisms leading to this behavior. Future possibilities and applications of these findings are discussed.

Alprazolam: pharmacokinetics, clinical efficacy, and mechanism of action.

Alprazolam, a triazolobenzodiazepine, is the first of this new class of benzodiazepine drugs to be marketed in the United States and Canada. It achieves peak serum levels in 0.7 to 2.1 hours and has a serum half-life of 12 to 15 hours. When given in the recommended daily dosage of 0.5 to 4.0 mg, it is as effective as diazepam and chlordiazepoxide as an anxiolytic agent. Its currently approved indication is for the treatment of anxiety disorders and symptoms of anxiety, including anxiety associated with depression. Although currently not approved for the treatment of depressive disorders, studies published to date have demonstrated that alprazolam compares favorably with standard tricyclic antidepressants. Also undergoing investigation is the potential role of alprazolam in the treatment of panic disorders. Alprazolam has been used in elderly patients with beneficial results and a low frequency of adverse reactions. Its primary side effect, drowsiness, is less than that produced by diazepam at comparable doses. Data on toxicity, tolerance, and withdrawal profile are limited, but alprazolam seems to be at least comparable to other benzodiazepines. Drug interaction data are also limited, and care should be exercised when prescribing alprazolam for patients taking other psychotropic drugs because of potential additive depressant effects.

Challenging the amphetamine challenge test: report of an antidepressant treatment study.

The primary goal of this study was to determine whether the amphetamine challenge test (ACT) response, as measured by a subjective rating scale, the How I Feel Scale (HIF), could predict antidepressant treatment outcome. Following a 1-day non-blind ACT with dextroamphetamine (d-AMPH), patients were treated double-blind for 6 weeks with either desipramine, alprazolam, or a desipramine-alprazolam combination. Regression (true score) analyses were carried out on pre- and post-ACT HIF scores and on baseline and end of study Hamilton Depression Rating Scale (HDRS) scores to determine the magnitudes of improvement measured in response to the ACT and antidepressant treatment, respectively. Regression analyses were performed on the residuals (true scores of improvement) to determine the best fitting (linear) prediction equation. Improvement in the HIF total score predicted HDRS improvement for the whole sample. Possible sources of error contributing to the outcome are identified and the results are discussed in relation to previous clinical investigations of the potential usefulness of the ACT as a predictor of antidepressant response.

Antidepressant or antianxiety? A study of the efficacy of antidepressant medication.

The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms, as measured by the Hamilton Rating Scale for Depression (HRSD) and the Hamilton Rating Scale for Anxiety (HRSA), respectively, after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy. Fifty-six subjects completed 6 weeks of treatment with either desipramine (n = 20), alprazolam (n = 18), or a desipramine-alprazolam combination (n = 18). The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score, and a better predictor than early improvement in the HRSA. Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group. This pattern of response differed from those observed for the other treatment groups. Desipramine-treated subjects showed gradual improvement over the course of the study, and the improvement in week 1 was not so strongly predictive of overall improvement. The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups. These findings are discussed in the context of the relationship between depression and anxiety, and potential implications for the treatment of these overlapping and often mixed syndromes.

An outpatient psychiatry program for offenders with mental disorders found not guilty by reason of insanity.

OBJECTIVE: Rehospitalization and criminal recidivism were examined among a group of offenders with mental disorders adjudicated as not guilty by reason of insanity and mandated to receive treatment in a forensic psychiatric outpatient program as a condition of release. METHODS: A retrospective chart review was conducted for 43 offenders with mental disorders who were acquitted as being not guilty by reason of insanity for the index offense and were active in the outpatient treatment program in 1996. Data were abstracted on sociodemographic, psychiatric, and criminal characteristics predating the index offense; rehospitalizations and new crimes and rearrests after the offense; and clinical and psychosocial functional outcomes after enrollment in the outpatient program. RESULTS: For the 43 patients, the mean length of stay in the program was 68 months, with a range of 4.9 months to 18.4 years. Almost two-thirds of the patients were diagnosed as having schizophrenia, schizoaffective disorder, or a nonaffective psychotic disorder; 58 percent had a comorbid substance use disorder, and 63 percent had an axis II diagnosis. Since program enrollment, 20 patients (47 percent) were rehospitalized at least once, and eight (19 percent) were rearrested or had committed a new crime. At the end of 1996, only nine (24 percent) were in full remission, and 26 (68 percent) showed at least one indicator of difficulty reintegrating into the community. CONCLUSIONS: Even after treatment in a specialized forensic program, this sample of offenders with serious mental disorders remained impaired symptomatically and functionally. Although avoidance of rehospitalization is considered a successful outcome, rehospitalization is preferable to rearrest for this forensic population.

Linking work and domestic problems with police suicide.

We reviewed the records of 134 police officers who had undergone their first fitness-for-duty evaluation at our center. Fifty-five percent admitted to previous suicide attempts. We examined possible contributing factors. A logistic regression model correctly classified 79.1% of subjects as to whether or not they attempted suicide. Results indicated that officers reporting marital problems were 4.8 times more likely to have attempted suicide, and 6.7 times more likely if they had been suspended. Interestingly, complaints of being administratively harassed were associated with a lower likelihood that an officer would attempt suicide. Variance explained due to age, race, gender, and substance use was nonsignificant.

Blood pressure reactivity in the evaluation of resting blood pressure and mood responses to pindolol and propranolol in hypertensive patients.

OBJECTIVE: The purpose of this exploratory study was to evaluate the relationship of blood pressure reactivity during exercise to treatment responsiveness to two commonly used beta-adrenergic blocking agents, propranolol and pindolol. DESIGN: Prospective, placebo-controlled, balanced, cross-over clinical trial. SETTING: University-affiliated medical center. PATIENTS: A convenience sample of 19 white male subjects with mild to moderate essential hypertension were studied. The mean age was 63.4 years (SD = 5.2). The mean resting systolic blood pressure (SBP) was 158.6 mm Hg (SD = 12.3) and mean resting diastolic blood pressure (DBP) was 96.4 mm Hg (SD = 8.6). They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. OUTCOME MEASURES: Resting blood pressure; blood pressure reactivity to exercise; self-report measures of depressive symptoms, and mood disturbances. INTERVENTION: Antihypertensive medication was tapered off and subjects were free of all prescription drugs for 2 weeks. Subjects were randomly assigned to propranolol-pindolol or pindolol-propranolol group. Each 4- to 6-week treatment phase was preceded by a 2-week placebo phase. At the end of the initial placebo phase and each active drug treatment phase, subjects were assessed for depression and mood disturbances by use of standardized measures and were given a graded exercise test on a cycle ergometer. Resting blood pressure was assessed weekly and before each exercise test. RESULTS: Significant relationships between DBP reactivity to exercise during the placebo phase and the degree of blood pressure and mood responsiveness to pindolol and propranolol treatment were observed. Subjects demonstrating high DBP reactivity required high doses of beta-blocker for resting DBP reduction, and these subjects showed the least change in mood at high doses. Similar patterns were found for the relationship of SBP reactivity and blood pressure and mood responsiveness to drug treatment, but these relationships were not statistically significant. CONCLUSIONS: DBP reactivity to exercise during the placebo phase provides unique information about the essential hypertensive patient. DBP reactivity and drug dose were important determinants of resting blood pressure and mood responsiveness to both pindolol and propranolol. DBP reactivity and perhaps SBP reactivity may be useful measures in the study of central adrenergic and peripheral cardiovascular pathophysiology.

Psychological aspects of sexual functioning among cleric and noncleric alleged sex offenders.

Cleric sexual misconduct with minors is a problem receiving increased attention from the media, victims groups, and church authorities. Mental health professionals are increasingly being asked to assist church and civil authorities to help better understand the problem of cleric sexual misconduct with minors. In the current study we compared self-reported sexual functioning among cleric alleged child molesters, noncleric alleged child molesters, and normal control subjects. We hypothesized clerics would differ from nonclerics and normals in reported sexual functioning. Our sample included 30 Roman Catholic clerics and 39 nonclerics who were alleged to have engaged in sexual misconduct with minors, and 38 normal control subjects, all of whom took the Derogatis Sexual Functioning Inventory (DSFI) as part of their forensic psychiatric evaluation. Our results indicated clerics were more likely to report fewer victims, older victims, and victims of male gender than noncleric alleged child molesters. Clerics differed from nonclerics and normal control subjects on several dimensions of self-reported sexual functioning. Lower offense rate histories among clerics suggest that, as a group, clerics may be less seriously psychologically disordered than noncleric child molesters. Low DSFI scores among Roman Catholic clerics may be accounted for in part by their unique training and socialization process. Future studies should attempt to study the influence of social desirability on DSFI scores. Normative data from nonoffending celibate clergy are needed.

Cycle of abuse and psychopathology in cleric and noncleric molesters of children and adolescents.

Sexual abuse in childhood is frequently reported among sex offenders and has been hypothesized to be one of a number of psychological factors etiologically related to perpetration of child molestation in adulthood. In the current study we examine a sample of cleric and noncleric admitted child molesters and normal control subjects in their exposure to sexual abuse in childhood and current psychopathology. Odds ratios for the association between exposure to sexual abuse and child molestation were obtained while adjusting for group differences in demographic and psychological characteristics. Results indicated exposure to sexual abuse in childhood was associated with becoming a child molester for both cleric and noncleric offenders (p < .0002). Nonclerics indicated more severe psychopathology than clerics. Sexual abuse in childhood is one of many risk factors for becoming a perpetrator of child molestation in adulthood for both cleric and noncleric child molesters. Noncleric offenders demonstrated more sociopathy and mental disorder in general while cleric offenders indicated more sexual conflictedness, suggesting different psychoetiologies of offending among cleric and noncleric child molesters.

Characteristics of women in jail and treatment orientations. A review.

Women who have been incarcerated are a high-risk group for criminal recidivism, and criminal justice statistics indicate that females are increasing in numbers more rapidly than the male detainee population. According to data from epidemiologic studies, incarcerated women are often young, single, mothers from ethnic minority backgrounds who have little education and poor work histories. Mental illness, drug abuse, and risky behaviors relating to contracting HIV/AIDS are common problems among female detainees. In this report, research into characteristics of women in jail and literature relating to treatment programs for incarcerated women are reviewed. Implications relating to treatment needs, program development, and further research are discussed. A case example and treatment intervention are presented based on this review.

Fibromyalgia: a study of family history of depression.

Previous research has suggested that some fibromyalgia may be part of an "affective spectrum disorder," pathophysiologically related to major depression. To examine the suspected association between fibromyalgia syndrome and depression, we conducted a family history study of depression among the first degree relatives (parents, siblings, and children) of two groups of probands with fibromyalgia, one with and one without a lifetime history of major depressive disorder. We tested the hypothesis that depression in patients with fibromyalgia is associated with a family history of depression. Major psychopathology in the probands was assessed with the Schedule for Affective Disorders and Schizophrenia and diagnosed using the Research Diagnostic Criteria. Forty fibromyalgia probands with and 14 fibromyalgia probands without a lifetime history of depression were interviewed about their parents, siblings, and children using the Family History Research Diagnostic Criteria format. Odds ratios were calculated, comparing the proportions of relatives with a history of depression in the two fibromyalgia proband groups. Lifetime histories of depression were found in 18% (n = 16) of the relatives of the probands with fibromyalgia and depression and in 9% (n = 25) of the relatives of the probands who did not have depression. Probands who had fibromyalgia and a history of major depression had more than twice the odds of having a relative who had depression than did the probands who had fibromyalgia but did not have a history of depression (odds ratio = 2.17 (95% confidence interval = 1.02-4.47)). These results suggest that depression in patients with fibromyalgia is associated with a family history of depression. Thus major depressive disorder in patients with fibromyalgia may be attributed more to their familial predisposition to depression than to a reaction to the pain and disability associated with fibromyalgia.