Urinary free cortisol levels among depressed men and women: differential relationships to age and symptom severity?

BACKGROUND: Preclinical and clinical models of depression suggest sex differences may be mediated at least in part, by differences in hormonal modulation of hypothalamic-pituitary-adrenal (HPA) axis activity. Unraveling the consequences of moderating influences from the effect of sexual dimorphism will be vital to elaborating models of pathophysiology. METHODS: The current study investigated urinary free cortisol (UFC) among younger adults with mild to moderate major depressive disorder to clarify the relationship with potential demographic and clinical moderators. RESULTS: Male patients had higher mean UFC levels than female patients. Moreover, significant interactions between age and severity were found among men, but not women. In contrast to prior findings, neither age nor severity effects on UFC levels were found among female patients. LIMITATIONS: Conclusions from the current study are limited by the absence of cortisol data from matched controls. Thus it was not possible to disentangle sex differences in baseline physiology from that of pathophysiological differences tied specifically to depression. CONCLUSIONS: Despite several methodological limitations, the interactions between sex and both age and severity in this large sample of depressed patients are suggestive of differential pathophysiology for regulation of UFC excretion, and could reflect a neuroprotective effect for estrogen among younger depressed women.

Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication.

BACKGROUND: We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition. METHOD: Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.

A family study of outpatients with borderline personality disorder and no history of mood disorder.

While several studies have examined psychiatric disorders in the relatives of individuals with borderline personality disorder, many of these studies have not employed a family study methodology and suffer from other methodological shortcomings. Thus, the conclusions from family data addressing the validity of borderline personality disorder, its relation to other conditions, and its distinction from mood disorders, continue to be debated. The present investigation employed a family study design with direct interviews with relatives, structured diagnostic interviews with both probands and relatives, and blind assessment of relatives. Rates of psychiatric disorders were examined in 563 relatives of outpatients with mood disorders (n = 119), 54 relatives of outpatients with borderline personality disorder and no history of mood disorder (n = 11), and 229 relatives of never psychiatrically ill controls (n = 45). Results indicate increased rates of mood disorders and personality disorders in the relatives of borderline probands compared with never psychiatrically ill controls. Familial aggregation of psychiatric disorders was generally similar for borderline personality and the mood disorder comparison group. The results suggest there may be common etiological factors between borderline personality disorder and mood disorders.

A prospective test of criteria for response, remission, relapse, recovery, and recurrence in depressed patients treated with cognitive behavior therapy.

The definitions that are commonly employed to describe the outcome of the depressive disorders are often used in inconsistent ways and remain largely untested. The lack of a standard and valid set of outcome definitions hinders the study of the naturalistic course and treatment of depressive disorders. In the present study, we operationalized definitions for response, remission, relapse, recovery, and recurrence and examined their validity in a sample of depressed patients treated with cognitive behavior therapy. Validity was evaluated by the ability of the definitions to predict subsequent outcome in acute treatment and during a 3 year follow-up period. All five definitions demonstrated moderate to excellent validity. Moreover, we were able to empirically distinguish response from remission, and relapse from recurrence, despite the frequent confusion of these terms in the literature. Several of the findings suggest that continued refinement of the outcome definitions may enhance validity even further.

Comorbidity between dysthymic and major depressive disorders: a family study analysis.

There is an extremely high rate of comorbidity between Dysthymic Disorder (DD) and Major Depressive Disorder (MDD). We used family study data to test four competing models of the relationship between DD, MDD, and comorbid DD/MDD: (1) DD, MDD, and DD/MDD are all variants of a single condition; (2) MDD and DD/MDD are similar, but differ from DD; (3) DD and DD/MDD are similar, but differ from MDD; and (4) all three conditions are distinct disorders. Subjects were the first-degree relatives of 22 outpatients with DD (n = 103), 45 outpatients with MDD (n = 207), 75 outpatients with comorbid DD/MDD (n = 343), and 45 normal controls (n = 229). Best-estimate diagnoses of relatives were derived using direct and family history interviews. Relatives of patients with DD and comorbid DD/MDD exhibited significantly higher rates of DD than relatives of patients with MDD and normal probands. The rate of comorbid DD/MDD was significantly higher in the relatives of patients with DD/MDD than the relatives of normal probands. Finally, the relatives of patients with MDD and comorbid DD/MDD exhibited significantly higher rates of MDD than the relatives of normal controls. Although none of the models received unambiguous support, some were more plausible than others.

Understanding the comorbidity between early-onset dysthymia and cluster B personality disorders: a family study.

OBJECTIVE: A number of studies have documented significant comorbidity between dysthymia and axis II personality disorders, particularly those grouped in cluster B. However, the nature of this comorbidity is poorly understood. The purpose of this investigation was to use the family study method to test five competing models of the comorbidity between early-onset dysthymia and cluster B personality disorders. METHOD: Proband groups consisted of subjects with early-onset dysthymia and a co-occurring cluster B personality disorder (N = 28), subjects with early-onset dysthymia without a cluster B personality disorder (N = 69), and a comparison group of subjects who had never been psychiatrically ill (N = 45). The groups were compared on rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia in their first-degree relatives (N = 675). RESULTS: The relatives of both subgroups of dysthymic probands exhibited higher rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia than the relatives of the never ill probands. In addition, the relatives of probands with comorbid dysthymia exhibited higher rates of cluster B personality disorders without dysthymia than the relatives of probands with noncomorbid dysthymia. CONCLUSIONS: This pattern of results is consistent with the notion that dysthymia and cluster B personality disorders co-occur because of shared etiological factors. This was the only one of five models of the comorbidity between dysthymia and cluster B personality disorders that was supported by the family data.

The subaffective-character spectrum subtyping distinction in primary early-onset dysthymia: a clinical and family study.

In 1983, Akiskal proposed that primary early-onset dysthymia should be divided into two subtypes: subaffective dysthymia, which is a subsyndromal form of major mood disorder; and character spectrum disorder, which is a form of personality disorder with secondary dysphoria. The present study attempted to validate this distinction. Akiskal's (1983) criteria were applied to a sample of 97 early-onset dysthymic outpatients, yielding groups of 41 subaffective and 56 character spectrum patients. Patients were evaluated using structured interviews for Axis I and II disorders, family history of psychopathology, and the early home environment, and a comprehensive battery of questionnaires. In addition, direct and family history interviews were conducted with their first-degree relatives. There was mixed support for Akiskal's typology. Consistent with the model, subaffectives exhibited higher rates of major depression, depressive symptoms, and a number of depressive personality and cognitive features. In addition, there was a higher rate of alcoholism among the relatives of character spectrum patients. However, contrary to Akiskal's model, the groups did not differ on gender, unstable personality disorders, family history of mood disorders, or the early home environment.

Family study of early-onset dysthymia. Mood and personality disorders in relatives of outpatients with dysthymia and episodic major depression and normal controls.

BACKGROUND: The nosological status of dysthymia has generated considerable controversy. The major issues include whether dysthymia should be classified as a form of mood or personality disorder and, if dysthymia is classified as a mood disorder, whether it is sufficiently distinct from major depression to warrant a separate category. METHODS: We conducted a family study of 97 outpatients with early-onset dysthymia, 45 outpatients with episodic major depression, and 45 normal controls, and their 882 first-degree relatives. Axis I and II disorders were assessed in relatives using direct and informant interviews and all available medical records. RESULTS: The rate of major depression in the relatives of early-onset dysthymic probands was significantly greater than in the relatives of normal controls and non-significantly greater than in the relatives of episodic major depressive probands. The rate of dysthymia was significantly greater in the relatives of dysthymic probands than in relatives of both major depressive probands and normal controls. Rates of most personality disorders were increased in the relatives of the dysthymic and major depressive probands compared with relatives of normal controls. In addition, the relatives of dysthymic probands had significantly higher rates of any personality disorder and any cluster B disorder than those of episodic major depressive probands, although these differences disappeared after controlling for Axis II comorbidity in the probands. Finally, dysthymic probands with and without a lifetime history of major depression did not differ on rates of psychiatric disorders in relatives. CONCLUSIONS: There is a strong familial relationship between dysthymia and major depression. However, dysthymia is also somewhat distinct in that it aggregates specifically in the families of patients with dysthymia. Finally, dysthymia and episodic major depression both appear to have a familial association with the personality disorders, although the link appears to be somewhat stronger for dysthymia.

Reports of the childhood home environment in early-onset dysthymia and episodic major depression.

This study addressed 2 questions: (a) is early-onset dysthymia associated with reports of a disturbed childhood home environment; and (b) can adverse early experiences account, at least in part, for the differing clinical presentations of dysthymia and major depression? Participants included 97 outpatients with early-onset dysthymia, 45 outpatients with episodic major depression, and 45 normal controls. The early home environment was assessed blind to diagnosis using both interview and self-report measures. Early-onset dysthymia patients reported significantly more physical and sexual abuse and poorer relationships with both parents than normal controls. In addition, patients with dysthymia reported having received significantly poorer parenting than those with episodic major depression. The results could not be accounted for by mood state effects, comorbidity with borderline and antisocial personality disorder, or comorbid major depression.

DSM-III-R axis II comorbidity in dysthymia and major depression.

OBJECTIVE: Dysthymia is generally believed to be associated with a high rate of DSM-III-R axis II comorbidity. However, it is unclear whether this rate is higher than that for other axis I disorders, how many dysthymic patients have personality disorders, and what the most common co-occurring axis II conditions are. METHOD: Ninety-seven outpatients with early-on-set dysthymia and 45 with episodic major depression were administered structured diagnostic interviews for axis I and II disorders. In addition, knowledgeable informants were independently interviewed about axis II conditions in the patients. RESULTS: A significantly greater proportion of dysthymic patients (60%) than patients with episodic major depression (18%) met criteria for a personality disorder. The most common axis II conditions among dysthymic patients were borderline, histrionic, and avoidant personality disorder. Informants' reports yielded similar results. CONCLUSIONS: These data indicate that early-onset dysthymia is associated with significantly greater axis II comorbidity than episodic major depression. Further work is necessary to elucidate the processes underlying this association.

Relationship of sociotropy/autonomy and dependency/self-criticism to DSM-III-R personality disorders.

Relationships between Beck's constructs of sociotropy/autonomy and Blatt's constructs of dependency/self-criticism and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) Axis II personality disorders were examined. Two measures of personality styles and a structured diagnostic interview for personality disorders were administered to 138 outpatients. Significant relationships were found between both sets of constructs and a number of personality disorders using both categorical and dimensional measures of Axis II psychopathology. These relationships were consistent with previous theory, supporting recent conceptualizations extending the range of psychopathology associated with these personality styles from depression to the personality disorders. However, the autonomy/self-criticism dimension was correlated with a broader range of personality disorder traits and diagnoses than anticipated.

Test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study.

OBJECTIVE: The present study examined the test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders. METHOD: As part of a series of family studies of outpatients with depressive and personality disorders, best-estimate diagnoses of relatives were derived in team diagnostic conferences held regularly over 4 years. Diagnoses were based on all available information, including direct interviews, family history data, and treatment records, and explicit guidelines were developed to resolve discrepancies between data sources. To evaluate the reliability of the team best-estimate diagnoses, 92 relatives were independently rediagnosed after a 2-year interval. RESULTS: The reliability of both axis I and II disorders was good to excellent. The results were similar for cases in which diagnoses were based on direct interviews plus informant data and cases in which diagnoses were based on informant data alone. CONCLUSIONS: These data indicate that the team consensus best-estimate diagnostic method can be applied consistently, even over an interval of several years.

Concordance between patients and informants on the personality disorder examination.

OBJECTIVE: Difficulties in the assessment of personality disorders and the burgeoning interest in axis II have led to increased use of informants when studying these conditions. The present study sought to evaluate the correspondence between patients and their informants on symptoms of personality disorders. METHOD: A total of 105 outpatients and knowledgeable informants were independently interviewed by using the Personality Disorder Examination, a widely used instrument for the full range of personality disorders. RESULTS: Diagnostic concordance between interviews was low (median kappa = -0.01), while correlations between dimensional scores were somewhat higher (median kappa = 0.36). Overall, patient interviews showed more pathology than interviews with informants. However, many of the symptoms obtained from informants were not reported by patients. CONCLUSIONS: These data suggest that patient-informant concordance for axis II disorders is poor for diagnoses but somewhat better for dimensional scores. There was no evidence that low agreement can be explained by patients attempting to present themselves in a favorable light. Further work is necessary to elucidate the reasons for discordance and determine which data source provides the most valid information.