Factors that differentiate early vs. later onset of major depression disorder

This report explores the relationship between age of first onset of major depression and other demographic and clinical features in the first 1500 patients entering the Sequenced Treatment Alternative to Relieving Depression (STAR*D) study. Outpatients, 18-75 years of age, with nonpsychotic major depressive disorder (MDD) from either primary care or psychiatric practices constitute the population. Age of onset was defined at study intake by asking patients to estimate the age at which they experienced the onset of their first major depressive episode. This report divides the population in terms of pre-adult (before age 18) onset and adult (age 18 or later) onset. The results suggest that MDD that begins before age 18 has a distinct set of demographic (female gender) and clinical correlates (longer duration of illness; longer current episodes; more episodes; more suicidality; greater symptom severity; more psychiatric symptoms associated with Axis I comorbidity; and more sadness, irritability, agitation and atypical symptom features), and it appears associated with significant psychosocial consequences (lower educational attainment and marriage rates). Thus, pre-adulthood onset MDD is a particularly severe and chronic condition.     

Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report.

OBJECTIVE: Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. DESIGN: Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). SETTING: Participants were enrolled from 23 psychiatric and 18 primary care settings. PARTICIPANTS: There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of > or =14. INTERVENTION: Participants received citalopram treatment for up to 14 weeks. MEASUREMENTS: Remission was defined by a 16-item Quick Inventory of Depressive Symptomatology-Self-Rated score of < or =5 at study exit. Side effects were measured by the Frequency, Intensity, and Burden of Side Effects Rating. RESULTS: Of 574 participants, 72.1% had earlier-onset depression and 27.9% had late-onset depression. Remission rates were not statistically different between earlier-onset (30.8%) and late-onset (31.9%) participants. Time to remission did not differ as well. CONCLUSION: The self-reported age at onset of the first MDE being after age 55 was not related to clinical outcomes for participants 55 to 75 years of age.     

Differences in the clinical characteristics of adolescent depressive disorders

Our objective was to analyze differences in clinical characteristics and comorbidity between different types of adolescent depressive disorders. A sample of 218 consecutive adolescent (ages 13-19 years) psychiatric outpatients with depressive disorders was interviewed for DSM-IV Axis I and Axis II diagnoses. We obtained data by interviewing the adolescents themselves and collecting additional background information from the clinical records. Lifetime age of onset for depression, current episode duration, frequency of suicidal behavior, psychosocial impairment, and the number of current comorbid psychiatric disorders varied between adolescent depressive disorder categories. The type of co-occurring disorder was mainly consistent across depressive disorders. Minor depression and dysthymia (DY) presented as milder depressions, whereas bipolar depression (BPD) and double depression [DD; i.e., DY with superimposed major depressive disorder (MDD)] appeared as especially severe conditions. Only earlier lifetime onset distinguished recurrent MDD from first-episode MDD, and newly emergent MDD appeared to be as impairing as recurrent MDD. Adolescent depressive disorder categories differ in many clinically relevant aspects, with most differences reflecting a continuum of depression severity. Identification of bipolarity and the subgroup with DD seems especially warranted. First episode MDD should be considered as severe a disorder as recurring MDD.     

Clinical features of bipolar depression versus major depressive disorder in large multicenter trials

OBJECTIVE: Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection. METHOD: The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder. RESULTS: Bipolar depression was associated with family history of bipolar disorder, an earlier age at onset, a greater previous number of depressive episodes, and eight individual symptom items on the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Fears were more common in patients with bipolar disorder, whereas sadness; insomnia; intellectual (cognitive), somatic (muscular), respiratory, genitourinary complaints; and depressed behavior were more common in patients with unipolar depression. A logistic regression model correctly classified 86.9% of the subjects. CONCLUSIONS: Bipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the initial diagnosis.     

Factors associated with chronic depressive episodes: a preliminary report from the STAR-D project

OBJECTIVE: To identify baseline sociodemographic and clinical factors associated with a current chronic major depressive episode (MDE). METHOD: Outpatients with major depressive disorder enrolled in 41 US primary or psychiatric care sites were divided into two groups based on self-report of current episode length (<24 or > or =24 months). Logistic regression models were used to identify factors associated with chronicity of current depressive episode. RESULTS: About 21.2% of 1380 subjects were in current, chronic MDEs. Older age, less education, lower income, no private insurance, unemployment, greater general medical illness burden, lower physical quality of life, concurrent generalized anxiety disorder, fewer prior episodes, and history of prior suicide attempts were all associated with chronic episodes. Blacks, Hispanics, and patients receiving care in primary as opposed to psychiatric care settings exhibited greater chronicity. CONCLUSION: Chronic depressive episodes are common and are associated with greater illness burden, comorbidity, socioeconomic disadvantage, and racial/ethnic minority status.     

Early age at onset of bipolar disorder is associated with more severe clinical features but delayed treatment seeking

OBJECTIVE: Our aim was to obtain a comprehensive view of differences between bipolar disorder (BD) patients with onset at early versus adult age in a representative study cohort. METHODS: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients were systematically screened for BD using the Mood Disorder Questionnaire (MDQ). A total of 191 bipolar I and II patients with a current DSM-IV episode were interviewed to obtain information about age at onset of mood symptoms, clinical course, treatment, comorbidity, and functional status. The patients were classified as either early onset (<18 years) or adult onset. RESULTS: One-third of subjects with BD (58/191, 30%) had early onset. This was associated with female gender, more lifetime psychotic symptoms, greater overall comorbidity, and a greater length of time from first episode to treatment. CONCLUSIONS: Although BD patients with early age at onset have more severe clinical features and illness course, the delays from first episode to treatment and to correct diagnosis are longer than for those with adult onset disorder. To reduce morbidity rates related to the most severe forms of BD, the recognition and diagnosis of BD during adolescence needs to be improved.     

Gender differences in incidence and age at onset of mania and bipolar disorder over a 35-year period in Camberwell, England

OBJECTIVE: Despite clear gender differences in the symptoms and course of bipolar affective disorder, studies investigating age at onset by gender have yielded inconsistent results. The authors investigated gender differences in age at onset and incidence of first-episode mania and bipolar disorder in an epidemiological catchment area in southeast London over a 35-year period. METHOD: All adult cases of first-episode psychosis, mania, or hypomania presenting to services in Camberwell, southeast London (1965-1999), were identified. Computerized diagnoses for these cases were generated by using the Operational Checklist for Psychotic Disorders program. Incidence rates and rate ratios of DSM-IV bipolar I disorder, first manic episode, by gender and age (10-year age-at-onset categories) were calculated. Differences in age at onset of first-episode mania and bipolar disorder by gender were examined by using univariate and multivariate analyses. RESULTS: Men had a significantly earlier onset of first-episode mania and bipolar disorder, with childhood antisocial behavior also being significantly associated, after multivariate analysis. Women had higher incidence rates of bipolar I disorder throughout adult life, except for early life (ages 16-25 years), although gender differences in individual age bands did not reach statistical significance. CONCLUSIONS: Men appear to have an earlier onset of mania and bipolar disorder than women. The association of male gender and childhood antisocial behavior with early-onset bipolar disorder raised the possibility of the existence of an early-onset subgroup.     

Clinical and demographic features of mood disorder subtypes

The aim of this study was to investigate demographic, clinical and symptomatologic features of the following mood disorder subtypes: bipolar disorder I (BP-I); bipolar disorder II (BP-II); major depressive disorder, recurrent (MDR); and major depressive episode, single episode (MDSE). A total of 1832 patients with mood disorders (BP-I=863, BP-II=141, MDR=708, and MDSE=120) were included in our study. The patients were assessed using structured diagnostic interviews and the operational criteria for psychotic illness checklist (n=885), the Hamilton depression rating scale (n=167), and the social adjustment scale (n=305). The BP-I patients were younger; had more hospital admissions; presented a more severe form of symptomatology in terms of psychotic symptoms, disorganization, and atypical features; and showed less insight into their disorder than patients in the other groups. Compared with the major depressive subgroups, BP-I patients were more likely to have an earlier age at onset, an earlier first lifetime psychiatric treatment, and a greater number of illness episodes. BP-II patients had a higher suicide risk than both BP-I and MDSE patients. MDSE patients presented less severe symptomatology, lower age at observation, and a higher number of males. The retrospective approach and the selection constraints due to the inclusion criteria are the main limitations of the study. Our data support the view that BP-I disorder is quite different from the remaining mood disorders from a demographic and clinical perspective, with BP-II disorder having an intermediate position to MDR and MDSE, that is, as a less severe disorder. This finding may help in the search for the biological basis of mood disorders.     

Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective

Objectives:  Distinguishing clinical characteristics of bipolar patients who have made a suicide attempt may help to identify at-risk individuals. We sought to identify such factors and to consider them within a stress-diathesis model of suicidal behavior.
Methods:  Patients with bipolar disorder (N = 96) were compared with respect to the presence or absence at baseline evaluation of a history of suicide attempt. We used multiple logistic regression analysis to assess the unique associations of independent variables to history of a past suicide attempt.
Results:  The regression analysis showed that a history of suicide attempt in bipolar disorder was associated with greater recent suicidal ideation, more psychiatric hospitalizations, lifetime aggressive traits and an earlier age at onset of a first mood episode.
Conclusions:  Aggressive traits and early treatment of mood disorders, especially major depressive episodes, are potential targets for suicide prevention in bipolar disorder.     

Polarity at illness onset in bipolar I disorder and clinical course of illness

Objectives:  Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder.
Methods:  We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210).
Results:  Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features.
Conclusions:  Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder.     

Drug use and the risk of major depressive disorder,alcohol dependence,and substance use disorders

BACKGROUND: The Children in the Community Study is a prospective longitudinal study investigating the association between early drug use (childhood, adolescence, and early 20s) and later psychiatric disorders (in the late 20s). METHODS: Using data from a community-based sample of 736 adults (50% female) from upstate New York, the subjects were interviewed at the mean ages of 14, 16, 22, and 27 years. Psychiatric disorders, measured by age-appropriate versions of the University of Michigan Composite International Diagnostic Interview, and participant's drug use were assessed. RESULTS: Adolescent and young adult tobacco use was significantly associated with an increased risk of alcohol dependence and substance use disorders at a mean age of 27 years, but not with new episodes of major depressive disorder. Earlier alcohol use significantly predicted later major depressive disorder, alcohol dependence, and substance use disorders in the late 20s, as did early marijuana use and other illicit drug use. Except for the effect of tobacco use on major depressive disorder, early drug use was significantly related to later psychiatric disorders, even after statistically controlling for age, sex, parental educational level, family income, and prior episodes of major depressive disorder and substance use disorders. CONCLUSIONS: Our results suggest that early drug use is associated with and predicts later psychiatric disorders. Preventive implications stem from the importance of studying a range of psychiatric disorders in the context of substance use assessed over a wide age range.     

Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry

OBJECTIVE: Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959. METHOD: Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. CONCLUSIONS: Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment.     

Aggression and substance abuse in bipolar disorder

Objectives:  The goal of this retrospective study was to examine factors differentiating persons with bipolar disorder who did or did not have comorbid lifetime substance use disorders (SUD) at an index assessment. We also explored the chronology of onset of mood and SUD.
Methods:  We studied 146 subjects with DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were compared on demographic and clinical measures.
Results:  Substance abuse disorders in this bipolar sample were associated with male sex, impulsive-aggressive traits, comorbid conduct and Cluster B personality disorders, number of suicide attempts and earlier age at onset of a first mood episode. In a multivariable logistic regression analysis, male sex and aggression and possibly earlier age at mood disorder onset were associated with SUD. In those with or without SUD, the first mood episode tended to be depressive and to precede the onset of SUD.
Conclusions:  In persons with bipolar disorder, an earlier age of onset and aggressive traits appear to be factors associated with later development of comorbid SUD.     

Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants.

BACKGROUND: We examined the hypothesis that a first depressive rather than manic episode in bipolar disorder might herald a subsequent course notable for greater burden of depressive symptoms. METHODS: We analyzed retrospective data on the polarity of first mood episode obtained from 704 bipolar I subjects entering the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Subjects with an initial manic or depressive episode and those in whom both poles occurred within the same year were compared. RESULTS: Depressive-onset bipolar disorder was more common in women and those with earlier onset of illness. Adjusting for these differences, it was significantly associated with more lifetime depressive episodes and a greater proportion of time with depression and anxiety in the year prior to study entry. CONCLUSIONS: Polarity of first mood episode may be useful in distinguishing subsets of bipolar patients at risk for a more chronic course.     

Personality disorder comorbidity in early-onset versus late-onset major depression in Japan

This study explored the comorbidity of DSM-III-R personality disorders in early-onset versus late-onset major depression in Japan. The subjects were 117 consecutive outpatients with major depression, with 26 classified as having an early onset (first depressive episode at age 22 or earlier) and 91 classified as having a late onset (first depressive episode at age 23 or later). Personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders after a 2-month antidepressant treatment. The results indicated that early-onset major depression was characterized by greater personality disorder comorbidity than late-onset major depression in Japan. Subjects with any one cluster A or B personality disorder were more prevalent in the early-onset group. In terms of each personality disorder, histrionic, narcissistic, and borderline patients were more prevalent, and the number of criteria met for schizotypal and cluster B personality disorders was significantly larger in early-onset major depression after corrections for age and gender. The results suggested that the higher prevalence of personality pathologies in early-onset major depression may reflect a higher likelihood to convert into bipolar disorders or a stronger impact of having experienced depressive episodes in young individuals. The possibility that the predisposing personality pathology may be different in early-onset and late-onset major depression is also discussed.     

Personality disorders in elderly patients with dysthymic disorder.

The authors evaluated personality disorders in elderly patients with DSM-IV dysthymic disorder (DD) to identify prevalent personality disorders and their clinical correlates. Outpatients (>/=60 years; N=76) with DD were evaluated; most were male (65.8%) and had late age at onset (>50 years: 60.5%). Axis II disorders were present in 31.2% of patients, with obsessive-compulsive personality disorder (OCD; 17.1%) and avoidant personality disorder (11.8%) being the most common. Personality disorders were associated with an earlier age at onset of depressive illness, greater lifetime history of comorbid Axis I disorders, greater severity of depressive symptoms, and lower socioeconomic status. Personality disorders occurred in a minority of elderly patients with DD and mainly comprised the obsessive-compulsive and avoidant subtypes, similar to reports of personality disorders in elderly patients with major depression. In contrast, young adults with DD have been shown consistently to have personality disorders at high frequency. Together with the predominance of late onset and the lack of psychiatric comorbidity, the current findings on personality disorders reinforce our view that DD in elderly patients is typically a different disorder from DD in young adults.     

Younger onset of depression is associated with greater suicidal intent

BACKGROUND: Age of onset of major depression seems to be dropping in Western nations. Early onset usually predicts a more serious illness with a relatively poor prognosis. Since depression is associated with suicide, this begs the question of whether early onset of depression is associated with the degree of intent of suicidal behaviour, and whether this relationship differs according to gender. METHODS: Relevant responses from 9,282 residents of the United States were drawn from a nationally representative community survey conducted in 2001 through 2003 using the W.H.O. version of the Composite International Diagnostic Interview. The primary outcome measure was the retrospectively determined age of first major depressive episode. RESULTS: Younger age of onset for depression was associated with higher levels of suicidal intent, irrespective of age at the time of interview. A significant interaction between level of intent and age at interview appeared to be accounted for by the later onset among those in the eldest cohort who reported an absence of suicidal behaviour. The influence of suicidal intent on onset of depression was greater for women than for men. CONCLUSIONS: The earlier the age of first symptoms of major depressive episode, the higher the degree of suicidal intent, irrespective of age at interview and gender, although the more pronounced trend for women suggests a greater sensitivity to underlying factors that may involve depression and lead to suicide risk.     

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.     

Major depressive disorder in the elderly: The relationship between age of onset and cognitive impairment

In order to determine if later age of onset of depression in the elderly is associated with increased cognitive impairment, the scores on the Mini-Mental State Examinations of 41 elderly depressed patients were correlated with the ages of onset of depression. All subjects, average age 74.7, were referred to a psychiatric day hospital for treatment of a major depressive disorder, and all scored at least 14 on the 17-item Hamilton Depression Rating Scale. The ages of first mental health contact and symptom onset were significantly negatively correlated with Mini-Mental State scores (p =0.021 and 0.035 respectively) after the confounding effect of age was adjusted for using partial correlations. The relation between late-onset depression and cognitive impairment lends support to the hypothesis that late-onset depressive disorders in the elderly may be associated with occult brain disease.     

Differences in diagnostic subtypes among patients with late and early onset of a single depressive episode

OBJECTIVE: It is unclear whether patients with late onset and patients with early onset present with different subtypes of depression. The aim of the study was to compare the prevalence of subtypes of ICD-10 single depressive episodes for patients with late onset (age >65 years) and patient with early onset (age < or = 65 years) in a nationwide sample of all patients discharged from psychiatric in- or outpatient settings. METHOD: All patients who got a diagnosis of a single depressive episode in a period from 1994-2002 at the end of the first outpatient treatment or at the first discharge from psychiatric hospitalisation ever in Denmark were identified in a nationwide register. RESULTS: In total, 18.192 patients were given a diagnosis of a single depressive episode at the first outpatient contact and 8.396 patients were given a diagnosis of a single depressive episode at the first psychiatric hospitalisation ever. Patients with late onset were more often women, more often presented with a severe depressive episode and more often with psychosis than patients with early onset, in both inpatient and outpatient treatment settings. No differences were found between patients with late and patients with early onset in the prevalence of depression with or without melancholic symptoms-in either of the treatment settings. CONCLUSIONS: Patients with a late onset first depressive episode are more often women and are clinically characterised by more severe depressions and a higher prevalence of psychosis than patients with early onset.