Childhood anhedonia symptoms and stressful life events predict the development of reward-related brain activity across adolescence.

The reward positivity (RewP) is an event-related potential that indexes reinforcement learning and reward system activation. The RewP has been shown to increase across adolescence; however, most studies have examined the RewP across two assessments, and no studies have examined within-person changes across adolescence into young adulthood. Moreover, the RewP has been identified as a neurobiological risk factor for adolescent-onset depression, but it is unclear whether childhood psychosocial risk factors might predict RewP development across adolescence. In a sample of 317 8- to 14-year-old girls (Mage = 12.4, SD = 1.8), the present study examined self-report measures of depression symptoms and stressful life events at baseline and the ΔRewP during the doors guessing task across three timepoints. Growth modeling indicated that, across all participants, the ΔRewP did not demonstrate linear change across adolescence. However, baseline anhedonia symptoms predicted within-person changes in the ΔRewP, such that individuals with low anhedonia symptoms demonstrated a linear increase in the ΔRewP, but individuals with high anhedonia symptoms had no change in the ΔRewP across adolescence. Similar patterns were observed for stressful life events. The present study suggests that childhood risk factors impact the development of reward-related brain activity, which might subsequently increase risk for psychopathology.

Social support buffers the effect of interpersonal life stress on suicidal ideation and self-injury during adolescence.

BACKGROUND: The effect of life stress on suicidal symptoms during adolescence is well documented. Stressful life events can trigger suicidality, but most adolescents are resilient and it is unclear which factors protect against the deleterious impact of stress. Social support is thought to be one such factor. Therefore, we investigated the buffering effect of specific sources of social support (parental and peer) on life stress (interpersonal and non-interpersonal) in predicting suicidal symptoms during adolescence. In order to test the specificity of this stress buffering, we also examined it with regard to dysphoric mood. METHOD: Data come from the Adolescent Development of Emotions and Personality Traits (ADEPT) Project, a cohort of 550 adolescent females aged 13.5-15.5 recruited from Long Island. Self-reported social support, suicidality, and dysphoria were assessed at baseline and suicidality and dysphoria were assessed again at 9-month follow-up. Life stress was assessed by interview at the follow-up. RESULTS: High levels of parental support protected adolescent girls from developing suicidal symptoms following a stressor. This effect was less pronounced for peer support. Also, social support did not buffer the pathogenic effects of non-interpersonal stress. Finally, social support did not buffer the effect of life stress on dysphoric symptoms. CONCLUSIONS: Altogether, our results highlight a distinct developmental pathway for the development of suicidal symptoms involving parental support that differs from the development of dysphoria, and signifies the importance and specificity of social support in protecting against suicidality in adolescent girls.

Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later.

BACKGROUND: Little is known about the predictive validity of disruptive mood dysregulation disorder (DMDD). This longitudinal, community-based study examined associations of DMDD at the age of 6 years with psychiatric disorders, functional impairment, peer functioning and service use at the age of 9 years. METHOD: A total of 473 children were assessed at the ages of 6 and 9 years. Child psychopathology and functional impairment were assessed at the age of 6 years with the Preschool Age Psychiatric Assessment with parents and at the age of 9 years with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. At the age of 9 years, mothers, fathers and youth completed the Child Depression Inventory (CDI) and the Screen for Child Anxiety Related Disorders, and teachers and K-SADS interviewers completed measures of peer functioning. Significant demographic covariates were included in all models. RESULTS: DMDD at the age of 6 years predicted a current diagnosis of DMDD at the age of 9 years. DMDD at the age of 6 years also predicted current and lifetime depressive disorder and attention-deficit/hyperactivity disorder (ADHD) at the age of 9 years, after controlling for all age 6 years psychiatric disorders. In addition, DMDD predicted depressive, ADHD and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive symptoms on the CDI, after controlling for the corresponding symptom scale at the age of 6 years. Last, DMDD at the age of 6 years predicted greater functional impairment, peer problems and educational support service use at the age of 9 years, after controlling for all psychiatric disorders at the age of 6 years. CONCLUSIONS: Children with DMDD are at high risk for impaired functioning across childhood, and this risk is not accounted for by co-morbid conditions.

Personality diatheses and Hurricane Sandy: effects on post-disaster depression.

BACKGROUND: According to diathesis-stress models, personality traits, such as negative emotionality (NE) and positive emotionality (PE), may moderate the effects of stressors on the development of depression. However, relatively little empirical research has directly examined whether NE and PE act as diatheses in the presence of stressful life events, and no research has examined whether they moderate the effect of disaster exposure on depressive symptoms. Hurricane Sandy, the second costliest hurricane in US history, offers a unique opportunity to address these gaps. METHOD: A total of 318 women completed measures of NE and PE 5 years prior to Hurricane Sandy. They were also assessed for lifetime depressive disorders on two occasions, the latter occurring an average of 1 year before the hurricane. Approximately 8 weeks after the disaster (mean = 8.40, s.d. = 1.48 weeks), participants completed a hurricane stress exposure questionnaire and a measure of current depressive symptoms. RESULTS: Adjusting for lifetime history of depressive disorders, higher levels of stress from Hurricane Sandy predicted elevated levels of depressive symptoms, but only in participants with high levels of NE or low levels of PE. CONCLUSIONS: These findings support the role of personality in the development of depression and suggest that personality traits can be useful in identifying those most vulnerable to major stressors, including natural disasters.

Affective modulation of the startle response among children at high and low risk for anxiety disorders.

BACKGROUND: Identifying early markers of risk for anxiety disorders in children may aid in understanding underlying mechanisms and informing prevention efforts. Affective modulation of the startle response indexes sensitivity to pleasant and unpleasant environmental contexts and has been shown to relate to anxiety, yet the extent to which abnormalities in affect-modulated startle reflect vulnerability for anxiety disorders in children has yet to be examined. The current study assessed the effects of parental psychopathology on affective modulation of startle in offspring. METHOD: Nine-year-old children (n = 144) with no history of anxiety or depressive disorders completed a passive picture viewing task in which eye-blink startle responses were measured during the presentation of pleasant, neutral, and unpleasant images. RESULTS: Maternal anxiety was associated with distinct patterns of affective modulation of startle in offspring, such that children with maternal histories of anxiety showed potentiation of the startle response while viewing unpleasant images, but not attenuation during pleasant images, whereas children with no maternal history of anxiety exhibited attenuation of the startle response during pleasant images, but did not exhibit unpleasant potentiation - even when controlling for child symptoms of anxiety and depression. No effects of maternal depression or paternal psychopathology were observed. CONCLUSIONS: These findings suggest that both enhanced startle responses in unpleasant conditions and failure to inhibit startle responses in pleasant conditions may reflect early emerging vulnerabilities that contribute to the later development of anxiety disorders.

Familial risk for distress and fear disorders and emotional reactivity in adolescence: an event-related potential investigation.

BACKGROUND: The late positive potential (LPP) is an event-related potential component that is sensitive to the motivational salience of stimuli. Children with a parental history of depression, an indicator of risk, have been found to exhibit an attenuated LPP to emotional stimuli. Research on depressive and anxiety disorders has organized these conditions into two empirical classes: distress and fear disorders. The present study examined whether parental history of distress and fear disorders was associated with the LPP to emotional stimuli in a large sample of adolescent girls. METHOD: The sample of 550 girls (ages 13.5-15.5 years) with no lifetime history of depression completed an emotional picture-viewing task and the LPP was measured in response to neutral, pleasant and unpleasant pictures. Parental lifetime history of psychopathology was determined via a semi-structured diagnostic interview with a biological parent, and confirmatory factor analysis was used to model distress and fear dimensions. RESULTS: Parental distress risk was associated with an attenuated LPP to all stimuli. In contrast, parental fear risk was associated with an enhanced LPP to unpleasant pictures but was unrelated to the LPP to neutral and pleasant pictures. Furthermore, these results were independent of the adolescent girls' current depression and anxiety symptoms and pubertal status. CONCLUSIONS: The present study demonstrates that familial risk for distress and fear disorders may have unique profiles in terms of electrocortical measures of emotional information processing. This study is also one of the first to investigate emotional/motivational processes underlying the distress and fear disorder dimensions.

Natural course of cannabis use disorders.

BACKGROUND: Despite its importance as a public health concern, relatively little is known about the natural course of cannabis use disorders (CUDs). The primary objective of this research was to provide descriptive data on the onset, recovery and recurrence functions of CUDs during the high-risk periods of adolescence, emerging adulthood and young adulthood based on data from a large prospective community sample. METHOD: Probands (n = 816) from the Oregon Adolescent Depression Project (OADP) participated in four diagnostic assessments (T1-T4) between the ages of 16 and 30 years, during which current and past CUDs were assessed. RESULTS: The weighted lifetime prevalence of CUDs was 19.1% with an average onset age of 18.6 years. Although gender was not significantly related to the age of initial CUD onset, men were more likely to be diagnosed with a lifetime CUD. Of those diagnosed with a CUD episode, 81.8% eventually achieved recovery during the study period. Women achieved recovery significantly more quickly than men. The recurrence rate (27.7%) was relatively modest, and most likely to occur within the first 36 months following the offset of the first CUD episode. CUD recurrence was uncommon after 72 months of remission and recovery. CONCLUSIONS: CUDs are relatively common, affecting about one out of five persons in the OADP sample prior to the age of 30 years. Eventual recovery from index CUD episodes is the norm, although about 30% of those with a CUD exhibit a generally persistent pattern of problematic use extending 7 years or longer.

DSM-5 disruptive mood dysregulation disorder: correlates and predictors in young children.

BACKGROUND: Despite the inclusion of disruptive mood dysregulation disorder (DMDD) in DSM-5, little empirical data exist on the disorder. We estimated rates, co-morbidity, correlates and early childhood predictors of DMDD in a community sample of 6-year-olds. METHOD: DMDD was assessed in 6-year-old children (n = 462) using a parent-reported structured clinical interview. Age 6 years correlates and age 3 years predictors were drawn from six domains: demographics; child psychopathology, functioning, and temperament; parental psychopathology; and the psychosocial environment. RESULTS: The 3-month prevalence rate for DMDD was 8.2% (n = 38). DMDD occurred with an emotional or behavioral disorder in 60.5% of these children. At age 6 years, concurrent bivariate analyses revealed associations between DMDD and depression, oppositional defiant disorder, the Child Behavior Checklist - Dysregulation Profile, functional impairment, poorer peer functioning, child temperament (higher surgency and negative emotional intensity and lower effortful control), and lower parental support and marital satisfaction. The age 3 years predictors of DMDD at age 6 years included child attention deficit hyperactivity disorder, oppositional defiant disorder, the Child Behavior Checklist - Dysregulation Profile, poorer peer functioning, child temperament (higher child surgency and negative emotional intensity and lower effortful control), parental lifetime substance use disorder and higher parental hostility. CONCLUSIONS: A number of children met DSM-5 criteria for DMDD, and the diagnosis was associated with numerous concurrent and predictive indicators of emotional and behavioral dysregulation and poor functioning.

Dyadic discord at baseline is associated with lack of remission in the acute treatment of chronic depression.

BACKGROUND: Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression. METHOD: Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology - Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables ('dyadic discord' v. 'no dyadic discord' defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of 14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of 7). RESULTS: Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (chi2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001]. CONCLUSIONS: Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

Discriminant validity, diagnostic utility, and parent-child agreement on the Screen for Child Anxiety Related Emotional Disorders (SCARED) in treatment- and non-treatment-seeking youth.

The Screen for Child Anxiety and Related Emotional Disorder (SCARED) may be differentially sensitive to detecting specific or comorbid anxiety diagnoses in treatment-seeking and non-treatment-seeking youth. We assessed the SCARED's discriminant validity, diagnostic utility, and informant agreement using parent- and self-report from healthy and treatment-seeking anxious youth (Study 1, N=585) and from non-treatment-seeking anxious youth (Study 2, N=331) diagnosed with generalized anxiety disorder (GAD), social anxiety disorder (SAD), or comorbid GAD+SAD. Among treatment-seeking youth, the SCARED showed good diagnostic utility and specificity, differentiating healthy, comorbid, and non-comorbid anxious youth. Child-parent agreement was modest: healthy child self-reports were higher than parent-reports whereas anxious child self-reports were similar or lower than parent-reports. Less consistent results emerged for diagnostic utility, specificity, and informant agreement among non-treatment-seeking youth. Given the number of non-treatment seeking anxious youth (N=33), generalizability of these findings may be limited. Together, results suggest informants may provide distinct information about children's anxiety symptoms.

Inventory identification of cyclothymia. IX. Validation in offspring of bipolar I patients.

We present the ninth in a series of validation studies that support the effectiveness of the General Behavior Inventory (GBI) in identifying cyclothymia. This study assessed the potential utility of the GBI in family and offspring studies by evaluating its ability to satisfy three prerequisites for use in such research: (1) identification of cyclothymia familially related to bipolar I disorder, (2) use with young adolescents, and (3) "insensitivity" to the effects of nonaffective psychopathology and parental nonaffective disorder in the offspring of control probands. The GBI and a blind, structured diagnostic interview were administered to 37 offspring of bipolar I patients and 21 offspring of psychiatric control patients, Twenty-seven percent of the offspring of bipolar patients, but none of the control offspring, were found to have bipolar forms of affective disorder, primarily cyclothymia (24%). Concordance between the GBI and interview-derived diagnoses was 95% to 97%, with 98% specificity and 80% to 90% sensitivity, depending on cutting score location. Together with the results of previous studies, the findings suggest that the GBI holds promise for the identification of cyclothymia in several research and clinical contexts.

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.

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.

Symptom criteria and family history in major depression.

The author examined the relationship between symptom criteria for major depression and family history of mood disorders in 82 outpatients with major depression and 27 outpatients with nonaffective disorders. The family members of depressed patients with six or more groups of DSM-III symptoms of major depression exhibited substantially higher rates of mood disorders than the family members of depressed patients with fewer than six groups of symptoms and the family members of patients with nonaffective disorders. These data suggest that stricter symptom criteria for major depression may define a more homogeneous phenotype, at least from the standpoint of familial aggregation.

Depressive personality in nonclinical subjects.

OBJECTIVE: This study explored the reliability and clinical correlates of the depressive personality in nonclinical subjects. In particular, the authors were interested in determining the relationship between depressive personality and mood disorders. METHOD: The subjects were 185 college students who were selected by using a battery of screening inventories assessing a variety of psychopathological symptoms and traits. The subjects were given structured diagnostic interviews that included a section on depressive temperament. RESULTS: There were significant relationships between depressive personality and lifetime. DSM-III diagnoses of major depression and dysthymia. However, the magnitude of the associations was modest, indicating that these are distinct, although overlapping constructs. In addition, the subjects with depressive personality (N = 36) had significantly greater impairment and a higher rate of mood disorders in their first-degree relatives than did the subjects without depressive personality (N = 149). Moreover, these results were evident even after the subjects with a lifetime history of mood disorder were excluded. CONCLUSIONS: These data suggest that depressive personality is a clinically important condition that is not subsumed by existing mood disorders categories but can be viewed as falling within the affective spectrum.

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.

Double depression and episodic major depression: demographic, clinical, familial, personality, and socioenvironmental characteristics and short-term outcome.

The authors compared 31 outpatients with double depression to 50 outpatients with episodic major depression. Patients with double depression exhibited significantly greater impairment, more severe depressive symptoms, greater comorbidity, more personality disturbance, lower levels of social support, more chronic strains, and higher rates of bipolar II and nonbipolar affective disorders in first-degree relatives. In addition, in a 6-month follow-up, the patients with double depression were significantly less likely to recover, and a higher proportion experienced hypomanic episodes than did patients with episodic major depression. These data provide strong support for the clinical significance of double depression.

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.

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.

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.