Biomedical subjects

D N Klein

Publications and source records attributed to D N Klein.

At least 19 recordsLinked to original sources

PubMed2003

Family study of co-morbidity between major depressive disorder and anxiety disorders.

BACKGROUND: Numerous studies have documented high rates of co-morbidity between major depressive disorder (MDD) and the anxiety disorders (ANX). However, the reason for this is unclear. Family studies provide one potentially useful approach for addressing this issue. METHOD: We explored six explanations of the co-morbidity between MDD and ANX using a family study of a large community sample of young adults and their first-degree relatives. Participants included 112 probands with a lifetime history of both MDD and one or more ANX, 290 probands with a history of MDD but no ANX, 43 probands with a history of one or more ANX but no MDD. 352 probands with no lifetime history of either MDD or ANX, and the probands' 2608 first-degree relatives. Probands were assessed using semi-structured diagnostic interviews on two occasions in adolescence and a third time at age 24. Diagnostic data on relatives were collected using both direct and family history interviews. RESULTS: Compared with controls, MDD aggregated in the families of probands with MDD, whether or not they had co-morbid ANX; ANX aggregated in the families of probands with ANX, regardless of whether they had co-morbid MDD; and co-morbid MDD/ANX aggregated only in the families of probands with both MDD and ANX. The relatives of probands with ANX alone had a significantly higher rate of ANX than the relatives of probands with MDD alone, although none of the other comparisons between the depressed and anxious groups were significant. CONCLUSIONS: This pattern of findings is largely, although not completely, consistent with the view that MDD and ANX are transmitted independently within families, and suggests that the comorbidity between MDD and ANX is caused by non-familial aetiological factors.

Adolescent↗

PubMed2003

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.

Adolescent↗

PubMed2003

Bipolar disorders during adolescence.

OBJECTIVE: To examine the incidence, correlates, course and family history of bipolar disorder (BD) and subthreshold BD in adolescents. METHOD: Structured diagnostic interviews were conducted with a large community sample of adolescents and their first-degree relatives, and the adolescents were re-evaluated as young adults. RESULTS: The first lifetime onset of BD and subthreshold BD almost always occurred in adolescence. Adolescent BD and subthreshold BD were associated with elevated impairment, comorbidity, and suicide attempts. Adolescents with BD were at increased risk for BD, and adolescents with subthreshold BD were at increased risk for major depressive disorder (MDD) in young adulthood. Relatives of BD adolescents had elevated rates of subthreshold BD and MDD, and relatives of subthreshold BD adolescents had elevated rates of BD and MDD. CONCLUSION: 'Classical' BD clearly exists in adolescence, but there is also a spectrum of milder bipolar conditions. Remediating and preventing BD in adolescents should be a high public health priority.

Adolescent↗

PubMed2001

A family study of major depressive disorder in a community sample of adolescents.

BACKGROUND: Family studies provide a useful approach to exploring the continuities and discontinuities between major depressive disorder (MDD) in children and adolescents and MDD in adults. We report a family study of MDD in a large community sample of adolescents. METHODS: Probands included 268 adolescents with a history of MDD, 110 adolescents with a history of nonmood disorders but no history of MDD through age 18 years, and 291 adolescents with no history of psychopathology through age 18 years. Psychopathology in their 2202 first-degree relatives was assessed with semistructured direct and family history interviews, and best-estimate diagnoses were derived with the use of all available data. RESULTS: The relatives of adolescents with MDD exhibited significantly elevated rates of MDD (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.46-2.31), dysthymia (HR, 1.79; 95% CI, 1. 11-2.87), and alcohol abuse or dependence (HR, 1.29; 95% CI, 1.05-1. 53), but not anxiety disorders, drug abuse or dependence, or antisocial and borderline personality disorder. In contrast, anxiety, substance use, and disruptive behavior disorders in adolescents were not associated with elevated rates of MDD in relatives. However, the relatives of probands with anxiety and substance use disorders exhibited elevated rates of anxiety and substance use disorders, respectively. CONCLUSIONS: The results provide evidence of the familial aggregation of adolescent MDD, and also indicate that there is a considerable specificity in the pattern of familial transmission. In addition, we found preliminary evidence of the familial aggregation of adolescent anxiety and substance use disorders.

Adolescent↗

PubMed2001

A construct validation study of the Response Styles Questionnaire Rumination Scale in participants with a recent-onset major depressive episode.

This study examined the construct validity and clinical utility of S. Nolen-Hoeksema's (1991) Response Styles Questionnaire (RSQ) Rumination scale. Eighty-eight participants with recent-onset major depressive episodes were assessed and followed for 6 months, using semistructured interviews and self-report inventories. The RSQ Rumination scale exhibited poor 6-month stability and appeared to be closely linked to participants' clinical status-mood state. The scale was significantly correlated with conceptually related constructs such as emotion-focused coping, negative affectivity-temperament, and self-criticism. However, baseline negative temperament and self-criticism predicted key aspects of the 6-month course and outcome of major depressive episodes, whereas baseline rumination did not. Finally, rumination appeared to be closely associated with the severity of the depressive episode, rather than defining a distinct clinical subtype.

Adolescent↗

PubMed2001

Outcome of dysthymic disorder at 5-year follow-up: the effect of familial psychopathology, early adversity, personality, comorbidity, and chronic stress.

OBJECTIVE: This study sought to identify predictors of course and outcome in dysthymic disorder. METHOD: Eighty-six outpatients with early-onset dysthymic disorder (before age 21) participated in a prospective 5-year follow-up study. Family history of psychopathology, early home environment, axis I and II comorbidity, social support, and chronic stress were assessed at baseline. The Longitudinal Interval Follow-up Evaluation and the Hamilton Depression Rating Scale were used in the follow-up assessments conducted at 30 and 60 months. RESULTS: Comorbid anxiety disorder, cluster C and depressive personality features, and chronic stress were associated with a lower rate of recovery from dysthymic disorder, while family history of bipolar disorder was associated with a higher probability of recovery. Family history of dysthymic disorder, poor childhood maternal and paternal relationships, childhood sexual abuse, cluster C features, neuroticism, a history of anxiety and eating disorders, and chronic stress predicted higher levels of depression at follow-up. Multivariate models indicated that almost all domains contributed to the prediction of course and outcome. CONCLUSIONS: The course and outcome of dysthymic disorder is best conceptualized within a multifactorial framework, with family history of psychopathology, early adversity, axis I and II comorbidity, and chronic stress all making important contributions.

Adult↗

PubMed2000

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.

BACKGROUND: Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. METHODS: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. RESULTS: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness). CONCLUSIONS: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

Adult↗

PubMed2000

The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of life events.

BACKGROUND: The present study examined whether stressful life events are associated with the development of major depressive episodes (MDEs) in a longitudinal, retrospective study of dysthymic and episodic major depressive disorders. METHODS: Sixty-seven outpatients with DSM-III-R dysthymia and 38 outpatients with non-chronic major depression were followed up 30-60 months after entry into the study. Follow-up assessments included a modified version of Paykel's (1997) Interview for Recent Life Events (IRLE) and Keller et al.'s (1987) Longitudinal Interval Follow-up Evaluation. Life events were assessed retrospectively in the 6 months before the most recent MDE or in the 6 months before follow-up for patients without a MDE. RESULTS: In dysthymic patients, MDEs were significantly associated with a new life event in the context of an ongoing chronic stressor. In episodic major depressive patients, relapses were associated with new life events regardless of an ongoing chronic stressor. LIMITATIONS: This was a retrospective study. It was also a conservative test of the association between life events and MDEs as the follow-up period over which life events were assessed was long, increasing the possibility of forgetting; events occurring less than 1 month before relapse were excluded to avoid confounding the event with the MDE; life events were assessed for a more distant time period for patients who experienced MDEs than those who did not; and an abbreviated version of the IRLE was used which may have failed to identify less severe events. CONCLUSIONS: This study suggests that life events may play a role in the onset of MDEs in persons with dysthymic disorder and those with major depressive disorder. Thus, clinicians should monitor dysthymic patients after a stressful life event, particularly if it occurs in the context of a chronic, ongoing stressor.

Adult↗

PubMed2000

Bipolar disorder during adolescence and young adulthood in a community sample.

OBJECTIVES: To compare the incidence and prevalence of bipolar disorder (BD) between adolescence and young adulthood; to explore the stability and consequences of adolescent BD in young adulthood; to determine the rate of switching from major depressive disorder (MDD) to BD; and to evaluate the significance of subsyndromal BD (SUB). METHODS: A large, randomly selected community sample (n = 1,507) received diagnostic assessments twice during adolescence, and a stratified subset (n = 893) was assessed again at 24 years of age. In addition, direct interviews were conducted with all available first-degree relatives. Five mutually exclusive groups, based on diagnoses in adolescence, were compared: BD (n = 17), SUB (n = 48), MDD (n = 275), disruptive behavior disorder (n = 49), and no-disorder (ND) controls (n = 307). RESULTS: Lifetime prevalence of BD was approximately 1% during adolescence and 2%, during young adulthood. Lifetime prevalence for SUB was approximately 5%. Less than 1%, of adolescents with MDD 'switched' to BD by age 24. Adolescents with BD had an elevated incidence of BD from 19 to 23 years, while adolescents with SUB exhibited elevated rates of MDD and anxiety disorders in young adulthood. BD and SUB groups both had elevated rates of antisocial symptoms and borderline personality symptoms. Compared to the ND group, adolescents with BD and SUB both showed significant impairment in psychosocial functioning and had higher mental-health treatment utilization at age 24 years of age. The relatives of adolescents with BD and SUB had elevated rates of MDD and anxiety disorders. The relatives of SUB probands had elevated BD, while the relatives of BD had elevated rates of SUB and borderline symptoms. CONCLUSIONS: Adolescent BD showed significant continuity across developmental periods and was associated with adverse outcomes during young adulthood. Adolescent SUB was also associated with adverse outcomes in young adulthood, but was not associated with an increased incidence of BD. Due to high rates of comorbidity with other disorders, definitive conclusions regarding the specific clinical significance of SUB must await studies with larger numbers of 'pure' SUB cases.

Adolescent↗

PubMed2000

Psychosocial predictors of the short-term course and outcome of major depression: a longitudinal study of a nonclinical sample with recent-onset episodes.

Three variables have been hypothesized to play important roles in prolonging the course of depressive episodes: a ruminative response style, significant interpersonal relationships, and childhood adversity. The authors examined whether these variables predicted the short-term course of major depressive disorder (MDD). Participants (n = 84) were college students with a recent-onset major depressive episode. Assessments included several interview and self-report measures, and data on interpersonal relationships were obtained from close confidants. Follow-up interviews were conducted 6 months later. After controlling for baseline severity, harsh discipline in childhood significantly predicted mean level of depression across the follow-up and level of depression at follow-up. Harsh discipline was also significantly associated with relapse but not with recovery. After controlling for baseline severity, rumination and the interpersonal variables did not predict the outcome of MDD.

Adolescent↗

PubMed2000

Predicting the 2 1/2-year outcome of dysthymic disorder: the roles of childhood adversity and family history of psychopathology.

Follow-up studies of dysthymic disorder (DD) indicate that demographic and clinical variables are not strong predictors of its outcome. The present study extended this literature by examining the relationship between the early home environment and family history of psychopathology and outcome in DD. Eighty-six outpatients with DD were followed up over a 30-month period using structured clinical interviews. A number of measures of childhood adversity and familial psychopathology assessed at baseline predicted outcome, even after controlling for baseline severity and clinical variables. The best predictors included a history of sexual abuse, quality of the patient's relationship with both parents, and higher familial loadings for drug abuse and Cluster A personality disorders. These findings indicated that childhood adversity and familial psychopathology have greater predictive utility for DD than for demographic and clinical variables.

Adult↗

PubMed2000

Parental psychopathology and reports of the childhood home environment in adults with early-onset dysthymic disorder.

In previous studies, patients with dysthymic disorder (DD) have reported significantly more adverse early home environments than patients with episodic major depressive disorder (MDD) and normal controls. However, DD is also associated with increased rates of mood and personality disorders in first-degree relatives, raising the possibility that the DD-early adversity relationship may be due to the confounding effects of parental psychopathology. The present study addressed this issue using a sample of 97 adult outpatients with early-onset DD, 45 adult outpatients with episodic MDD, and 45 normal controls, and their first-degree relatives. The early home environment was assessed with semi-structured interviews and self-report inventories. Parental psychopathology was assessed using semi-structured direct and family history interviews, and diagnoses were assigned using the best-estimate procedure. Results indicated that parental mood and personality disorders were strongly associated with probands' reports of early adversity. However, patients with DD continued to differ significantly from patients with episodic MDD and normal controls after controlling for parental psychopathology.

Adolescent↗

PubMed2000

Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in young adults.

OBJECTIVE: The primary purpose was to identify factors related to the recurrence of major depressive disorder during young adulthood (19-23 years of age) in a community sample of formerly depressed adolescents. METHOD: A total of 274 participants with adolescent-onset major depressive disorder were assessed twice during adolescence and again after their 24th birthday. Lifetime psychiatric information was obtained from their first-degree relatives. Adolescent predictor variables included demographic characteristics, psychosocial variables, characteristics of adolescent major depressive disorder, comorbidity, family history of major depressive disorder and nonmood disorder, and antisocial and borderline personality disorder symptoms. RESULTS: Low levels of excessive emotional reliance, a single episode of major depressive disorder in adolescence, low proportion of family members with recurrent major depressive disorder, low levels of antisocial and borderline personality disorder symptoms, and a positive attributional style (males only) independently predicted which formerly depressed adolescents would remain free of future psychopathology. Female gender, multiple major depressive disorder episodes in adolescence, higher proportion of family members with recurrent major depressive disorder, elevated borderline personality disorder symptoms, and conflict with parents (females only) independently predicted recurrent major depressive disorder. Comorbid anxiety and substance use disorders in adolescence and elevated antisocial personality disorder symptoms independently distinguished adolescents who developed recurrent major depressive disorder comorbid with nonmood disorder from those who developed pure major depressive disorder. CONCLUSIONS: Formerly depressed adolescents with the risk factors identified in this study are at elevated risk for recurrence of major depressive disorder during young adulthood and therefore warrant continued monitoring and preventive or prophylactic treatment.

Adolescent↗

PubMed2000

Five-year course and outcome of dysthymic disorder: A prospective, naturalistic follow-up study.

OBJECTIVE: There have been few naturalistic follow-up studies of dysthymic disorder. This study describes the 5-year course and outcome of dysthymic disorder. METHOD: The authors conducted a prospective, longitudinal follow-up study of 86 outpatients with early-onset dysthymic disorder and 39 outpatients with episodic major depressive disorder. Follow-ups, conducted 30 and 60 months after entry into the study, rated patients on the Longitudinal Interval Follow-Up Evaluation and the Modified Hamilton Rating Scale for Depression. RESULTS: The estimated 5-year recovery rate from dysthymic disorder was 52.9%. Among patients who recovered, the estimated risk of relapse was 45.2% during a mean of 23 months of observation. Patients with dysthymic disorder spent approximately 70% of the follow-up period meeting the full criteria for a mood disorder. During the course of the follow-up the patients with dysthymic disorder exhibited significantly greater levels of symptoms and lower functioning and were significantly more likely to attempt suicide and to be hospitalized than were patients with episodic major depressive disorder. Finally, among patients with dysthymic disorder who had never experienced a major depressive episode before entry into the study, the estimated risk of having a first lifetime major depressive episode was 76.9%. CONCLUSIONS: Dysthymic disorder is a chronic condition with a protracted course and a high risk of relapse. In addition, almost all patients with dysthymic disorder eventually develop superimposed major depressive episodes. Although patients with dysthymic disorder tend to show mild to moderate symptoms, from a longitudinal perspective, the condition is severe.

Adolescent↗

PubMed2000

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.

Adult↗

PubMed2000

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.

Adult↗

PubMed1999

Depressive personality in the relatives of outpatients with dysthymic disorder and episodic major depressive disorder and normal controls.

BACKGROUND: This study examined whether there is a familial relationship between depressive personality and the mood disorders. METHOD: Rates of depressive personality were compared in 161 relatives of outpatients with dysthymic disorder (DD), 75 relatives of outpatients with non-chronic major depressive disorder (MDD), and 90 relatives of normal controls. All probands and relatives were evaluated using structured diagnostic interviews for Axis I disorders and depressive personality traits. RESULTS: The relatives of patients with DD exhibited a significantly higher rate of depressive personality than the relatives of normal controls, while the relatives of patients with MDD fell in between, and did not differ from, the other two groups. These results held after controlling for a lifetime history of mood disorder in the relatives, and could not be explained by an increased rate of depressive personality in the DD probands. LIMITATIONS: The sample size was modest, comorbid non-mood Axis I and II disorders in the relatives were not controlled, and DSM-IV criteria for depressive personality disorder were not yet available at the time the study was undertaken. CONCLUSION: These findings are consistent with the view that depressive personality is part of a spectrum of mood disorders with a shared familial liability, but suggest that this link is strongest with chronic forms of depression such as DD and double depression.

Adult↗

PubMed1999

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response.

BACKGROUND: The clinical and etiological significance of the early-late onset distinction in chronic major depressive disorder was explored. METHOD: Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS: Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. LIMITATIONS: Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. CONCLUSIONS: Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Adult↗