Thirty-month naturalistic follow-up study of early-onset dysthymic disorder: Course, diagnostic stability, and prediction of outcome.

Dysthymic disorder (DD) is defined and distinguished from major depressive disorder (MDD) largely on the basis of its course. Surprisingly, however, there have been few prospective, longitudinal studies of the naturalistic course of DD. This article reports the major findings from a prospective, longitudinal 30-month follow-up study of 86 outpatients with early-onset DD (EOD) and 39 outpatients with episodic MDD. Follow-up assessments included the Longitudinal Interval Follow-Up Evaluation and Hamilton Rating Scale for Depression. Compared with patients with episodic MDD, patients with EOD exhibited less improvement from the baseline evaluation and were more symptomatic at follow-up. Only 39% of patients with EOD recovered from DD during the follow-up period. The diagnosis of DD was fairly stable, with 52% of the EOD group meeting full criteria for DD at follow-up. These data provide prospective confirmation of the chronic course of DD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Offspring at high and low risk for depression and anxiety: mechanisms of psychiatric disorder

OBJECTIVES: To examine the effect of parental psychiatric diagnosis on the risk of psychiatric disorder in their offspring and to determine mediators and independent predictors of psychiatric disorder in offspring. METHOD: The sample consisted of 145 offspring (between the ages of 6 and 24 years, who were directly interviewed) of probands with early-onset (before age 30 years) major depressive disorder (MDD) without panic, panic disorder with and without major depression, and a normal, never psychiatrically ill control group who were part of a large study conducted to determine the relationship between panic disorder and major depression. RESULTS: The risk for offspring MDD was increased by proband recurrent early-onset MDD and coparent alcohol abuse. Chaotic family environment was the only independent predictor of dysthymia. The risk for offspring "any anxiety" disorder was increased by proband recurrent early-onset MDD and coparent impaired functioning. The association between MDD in proband and "panic spectrum" disorder in offspring was accounted for by chaotic family environment. CONCLUSION: Recurrent parental MDD has consistently been shown to be a strong risk factor for offspring MDD. Family environment plays an important role in low-level anxiety symptoms and dysthymia. Clinicians treating adults should be alert to risk factors for their offspring and to appropriate targets for early intervention.     

Clinical analysis of internal carotid artery aneurysms with reference to classification and clipping techniques

OBJECTIVE: To determine the differential effects of parental major depression (MDD) on psychopathology of childhood, adolescent, and early-adult onset in offspring. METHOD: One hundred eighty-two offspring from 91 families in which one or more parents or neither parent had MDD were followed for more than 10 years and blindly reassessed by means of a structured diagnostic instrument. RESULTS: Parental MDD is associated with increased risk in offspring of childhood-onset MDD (eightfold), anxiety disorder (threefold), conduct disorder (fivefold), and early-adult-onset MDD (fivefold) but not adolescent-onset MDD, where there is a marked increase in risk, particularly in girls, regardless of parental diagnosis. These findings were not explained by parental comorbidity, but the association with MDD was explained by parental age at onset of MDD--there was a 13-fold increase in childhood-onset MDD and a 7-fold increase in adult-onset MDD in offspring of parents with MDD of early (before age 30 years) onset. CONCLUSION: Childhood- and early-adult-onset MDD may be etiologically homogeneous and familial subtypes. The reason for the high incidence of adolescent-onset MDD, particularly in girls, regardless of parental diagnosis, needs to be determined. The childhood offspring of depressed parents are a potential target for evaluation, especially when the parent had an early-onset depression.     

Association of Parental Depression With Psychiatric Course From Adolescence to Young Adulthood Among Formerly Depressed Individuals.

The authors examined whether parental major depressive disorder (MDD) is associated with course of depression and other psychopathology among formerly depressed adolescents as they enter adulthood. The sample consisted of 244 individuals (age 24) in a longitudinal study who had experienced MDD by 19. Maternal MDD was associated with MDD recurrence, chronicity and severity, anxiety disorders, and (among sons only) lower psychosocial functioning in offspring between the ages of 19 and 24. Paternal MDD was associated with lower functioning. Sons of depressed fathers had elevated suicidal ideation and attempt rates in young adulthood. Recurrent paternal MDD was associated with depression recurrence in daughters but not sons. The impact of parental MDD on offspring could not be attributed to characteristics of the offspring's depression prior to age 19. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability and validity of depressive personality disorder

OBJECTIVE: Depressive personality disorder was introduced into DSM-IV's appendix amid controversy. While that disorder appears to be a reliable and valid one, the authors offer new data about its relationship to major depression, dysthymic disorder, and other personality disorders. METHOD: The authors assessed 54 subjects with early-onset, long-standing mild depressive features for depressive personality disorder, axis I and axis II disorders, family history, and treatment history; they conducted follow-up interviews 1 year after the baseline assessment. Subjects with (N=30) and without (N=24) depressive personality disorder were characterized and compared in terms of those variables. RESULTS: Although depressive personality disorder and dysthymia co-occurred in some subjects, 63% of subjects with depressive personality disorder did not have dysthymia, and 60% did not have current major depression. Although subjects with depressive personality disorder were more likely than the mood disorder comparison group to have another personality disorder, 40% had no such disorder. Contrary to study hypotheses, mood disorder was not more common in first-degree relatives of subjects with depressive personality disorder than in relatives of the comparison group. Subjects with and without depressive personality disorder had similar rates of past treatment with medication and psychotherapy; however, the duration of psychotherapy was significantly longer for subjects with than for those without depressive personality. The depressive personality diagnosis was relatively stable over the 1-year follow-up period. CONCLUSIONS: Depressive personality disorder appears to be a relatively stable condition with incomplete overlap with axis I mood disorders and personality disorders. Further studies are needed to better characterize its treatment response and relationship to axis I mood disorders.     

The many faces of depression following spousal bereavement

While it is becoming increasingly clear that mood disorders tend to be chronic, intermittent and/or recurrent conditions with different manifestations over time, little is known of the variability or course of mood disorders that are associated with severe psychosocial stress. This paper reports on the prevalence and course of major, minor, and subsyndromal depressions in 328 widows and widowers followed prospectively from 2 to 25 months following one of the most disruptive of all naturally occurring stressors, spousal bereavement. The results are consistent with the following conclusions: (1) past major depression (prior to the death) predicts an increased risk for major depression following bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts future depression throughout the unipolar depressive spectrum; (3) subsyndromal and minor depression stand between major depression, on the one hand, and no depression, on the other, in terms of their effects on overall adjustment to widowhood. Thus, the results support the validity of subsyndromal depression, and that the three subgroups (major, minor and subsyndromal depression) are pleiomorphic manifestations of the same unipolar depression disorder.     

Trauma and chronic depression among patients with anxiety disorders

This study examined the relationship between a history of trauma and the features and persistence of major depression (MDD) in patients with anxiety disorders. The study found that, among 408 patients with an anxiety disorder and past or current MDD, those patients who reported a history of trauma had a greater number of previous episodes of major depression than those patients without trauma histories. Also, of 174 patients with an anxiety disorder and current major depression, patients who reported histories of trauma, compared with patients who did not report such experiences, were less likely to remit from MDD over a 5-year period. Results suggest that a history of trauma is a risk factor for chronic depression.     

Psychiatric comorbidity among referred juveniles with major depression: fact or artifact?

OBJECTIVE: The high levels of psychiatric comorbidity reported in juveniles meeting operational definitions of depressive disorders raise both substantive and methodological concerns about whether depression with comorbid disorders should be classified as two disorders or as different manifestations of the same condition. Our purpose was to clarify issues of diagnostic heterogeneity and diagnostic overlap in juvenile depression. METHOD: The sample consisted of consecutively referred children and adolescents (N = 424) comprehensively evaluated with structured diagnostic interviews and psychosocial assessments. RESULTS: A clinical picture compatible with the diagnosis of major depression was identified in 40% of these referred youths. Children meeting criteria for major depression had prototypical symptoms of the disorder, a chronic course, and severe psychosocial dysfunction. In addition, they frequently met criteria for attention-deficit hyperactivity disorder, conduct disorder, and anxiety disorders. These comorbidity findings were not due to symptom overlap among major depression and the co-occurring disorders. For the most part, comorbid disorders preceded the onset of major depression by several years. CONCLUSIONS: Juvenile depression has a chronic course, severe dysfunction, and high levels of psychiatric comorbidity. Despite symptom overlap, our work suggests that major depression and other conditions may represent different disorders.     

The relationship between panic disorder and major depression. A new family study

OBJECTIVE: The comorbidity between panic disorder and major depression (MDD) in individuals has been amply documented. However, data from family studies to determine whether panic disorder and MDD aggregate separately or together in families have been inconclusive, in part because of the absence of studies with the full range of proband groups. This report presents results from a family study with the necessary mutually exclusive groups: panic disorder without MDD, panic disorder with MDD, MDD without panic disorder, and normal controls. METHODS: Diagnostic information was obtained from 193 probands and 1047 of their adult relatives with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version for Anxiety Disorders by direct interview, and/or from multiple informants, without knowledge of proband diagnoses. Best-estimate diagnoses were based on all available information by clinicians independently of data collection and without knowledge of probands' and other relatives' status. RESULTS: Findings indicated the specific and independent transmission of panic disorder and MDD, the separation of panic disorder from MDD, and the nonfamilial nature of late-onset MDD. The pattern of results was unaffected by the use of different diagnostic criteria, number of informants, interview status of relatives, presence of substance abuse or agoraphobia or the sequence of MDD and panic disorder in probands, or whether probands were selected from treatment clinics or community sample. CONCLUSIONS: We conclude that panic disorder and MDD are separate disorders with substantial co-occurrence in individuals, and that panic comorbid with MDD is not a single, distinct disorder. Finally, we illustrate an approach to examining comorbidity in family data through analysis of mutually exclusive, parallel diagnoses in probands and relatives.     

Psychosocial correlates of childhood anxiety disorders

OBJECTIVE: This study explored psychosocial and "environmental" correlates of childhood anxiety disorders. The study examined relationships among parental psychiatric symptomatology, perceived family environment, temperament, and self-competence in children with a DSM-III-R anxiety disorder. METHOD: A community sample of third through sixth graders was screened initially for symptoms of test anxiety. Those with high and low scores were administered the Anxiety Disorders Interview Schedule for Children. Three groups (childhood anxiety disorder, test-anxious only, and normal controls) were identified and compared on the psychosocial variables. RESULTS: Children with an anxiety disorder had greater impairment on the indices of perceived self-competence and temperamental flexibility than controls, with the test-anxious children showing intermediate, yet significant, levels of disturbance. There was a trend for children with an anxiety disorder to describe their families as less promoting of independence than the other groups. Finally, measures of parental psychiatric symptomatology revealed more obsessive-compulsive symptoms for the fathers of both the anxiety disorder and test-anxious children compared with controls. CONCLUSIONS: Results are consistent with previous findings suggesting the familial transmission of anxiety disorders and recent speculations regarding a relationship between behavioral inhibition, environmental control, and anxiety. Further research may isolate psychosocial and family environmental factors as instrumental treatment targets in the management of childhood anxiety disorders.     

Dysthymia in the offspring of parents with primary unipolar affective disorder.

This study examined whether there is a familial relation between primary early-onset dysthymia and major affective disorder. In addition, it explored the prevalence of other forms of psychopathology and social impairment in the adolescent and young adult offspring of patients with primary unipolar affective disorder. Subjects included 47 offspring of patients with primary unipolar depression, 33 offspring of patients with chronic orthopedic and rheumatological conditions, and 38 offspring of randomly selected community controls with no personal or family history of psychiatric disorder. All offspring received structured diagnostic interviews. Diagnoses were derived blind to parental group by using multiple sets of diagnostic criteria. The offspring of unipolar patients exhibited significantly higher rates of affective disorder, major depression, and dysthymia than did the offspring of medical and normal controls. The groups did not differ on rates of nonaffective disorders. Parental characteristics associated with dysthymia in offspring included chronic depression, age of onset of major depression, number of hospitalizations, and multiple family members with major affective illness. These results support the view that at least some forms of early-onset dysthymia are variants of major affective illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glial reduction in the subgenual prefrontal cortex in mood disorders

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann's area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.     

Complex patterns of immediate early gene induction in rat brain following brightness discrimination training and pseudotraining

Data presented during the 1996 CINP President's Workshop supported the conclusion that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder consisting of a cluster of depressive subtypes existing in a relatively homogeneous symptomatic clinical continuum, extending from subsyndromal depressive symptomatology (SSD) through minor depressive episode, dysthymic disorder, major depressive episode and double depression. This indicates that common unipolar depressive subtypes can be conceptualized as alternate forms or different symptomatic phases of the same parent illness. Although there appears to be great overlap across time in the symptomatological expressions of these clinical depressive subtypes, they may be derived from different etiological and genetic factors. The one exception may be major depressive episode with psychotic features, which exists on a severity continuum with other subtypes of unipolar MDD, but does not appear to be on a symptomatic continuum with dysthymic, subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder represent clinically significant depressive subtypes, which are commonly observed during the course of illness of patients with unipolar major depressive illness. Compared to no depressive symptoms, SSD is associated with harmful dysfunction, as evidenced by significant increases in psychosocial impairment, signifying that SSD is an active, inter-episode disease state of unipolar major depressive disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may also represent potent risk factors for rapid depressive episode relapse. In the aggregate, these findings and conclusions have broad and important implications for diagnostic and treatment strategies of unipolar MDD.     

Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications

BACKGROUND: Increasing attention has been directed in recent years to the detection and treatment of psychiatric co-morbidity among depressed individuals. The overlap of social phobia (SP) and avoidant personality disorder (APD) has been well recognized and a relationship between these disorders and depression has been suggested. METHODS: The pattern and clinical implications of co-morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM-III-R criteria, were studied among 243 out-patients presenting with depression. RESULTS: Overall, 26.7% of adults in our sample with MDD met criteria for SP and 28.4% for APD. Almost two-thirds of depressed adults meeting criteria for social phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed adults who met criteria for both SP+APD exhibited a significantly higher proportion of atypical depression (54.8%) compared with those with neither SP nor APD (31.1%). Among depressed patients, the co-occurrence of SP with APD was also associated with an earlier age of onset of MDD, a greater number of comorbid Axis I diagnoses, and greater impairment of social adjustment and assertiveness. CONCLUSIONS: Results confirm the overlap of SP and APD in a depressed population and the high prevalence of these disorders in MDD. They suggest that depressed individuals with both SP and APD but not SP alone are at particularly high risk for atypical depression and for social dysfunction in excess of that caused by a current major depression.     

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. OBJECTIVE: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. RESULTS: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. CONCLUSIONS: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.     

Is attention deficit hyperactivity disorder familial?

Using two sources of data, we review methodologic issues pertinent to family studies of attention deficit hyperactivity disorder to evaluate whether such studies define attention deficit hyperactivity disorder as a familial disorder. We systematically evaluate the relevant literature and provide a detailed overview of the Massachusetts General Hospital family-genetic studies of attention deficit disorder as defined in DSM-III and attention deficit hyperactivity disorder as defined in DSM-III-R. The available literature, and our double-blind, controlled studies indicate that attention deficit disorder and attention deficit hyperactivity disorder are familial. Moreover, the pattern of transmission of comorbid disorders suggests that attention deficit hyperactivity disorder is, from a familial perspective, distinct from anxiety disorders and learning disabilities. In contrast, attention deficit hyperactivity disorder with conduct disorder appears to be a familial subtype, and major depression appears to be a variable expression of the familial predisposition to attention deficit hyperactivity disorder. Although the available literature provides strong evidence for the familial transmission of attention deficit hyperactivity disorder, the mode of transmission requires further clarification. In addition, attention deficit hyperactivity disorder appears to be genetically heterogeneous, indicating that more work is needed to delineate genetically homogeneous subtypes and to describe the range of expression of their underlying genotypes. Family-genetic studies will continue to clarify the etiology and nosology of attention deficit hyperactivity disorder.     

Adolescent psychopathology: II. Psychosocial risk factors for depression.

In a prospective study of adolescent depression, adolescents (N?=?1,508) were assessed at Time 1 and after 1 yr (Time 2) on psychosocial variables hypothesized to be associated with depression. Most psychosocial variables were associated with current (n?=?45) depression. Formerly depressed adolescents (n?=?217) continued to differ from never depressed controls on many of the psychosocial variables. Many of the depression-related measures also acted as risk factors for future depression (n?=?112), especially past depression, current other mental disorders, past suicide attempt, internalizing behavior problems, and physical symptoms. Young women were more likely to be, to become, and to have been depressed. Controlling for the psychosocial variables eliminated the gender difference for current and future but not for past depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Children of affectively ill parents: a review of the past 10 years

OBJECTIVE: To review the literature investigating the effects of parental affective illness on children over the past decade. METHOD: A computerized search of articles published over the past 10 years was completed. Articles were reviewed and relevant studies are presented. RESULTS: Over the course of the past 10 years a number of longitudinal studies have confirmed that children of affectively ill parents are at a greater risk for psychiatric disorders than children from homes with non-ill parents. Life table estimates indicate that by the age of 20 a child with an affectively ill parent has a 40% chance of experiencing an episode of major depression. Children from homes with affectively ill parents are more likely to exhibit general difficulties in functioning, increased guilt, and interpersonal difficulties as well as problems with attachment. Marital difficulties, parenting problems, and chronicity and severity of parental affective illness have been associated with the increased rates of disorder observed in these children. CONCLUSION: The presence of depression in parents should alert clinicians to the fact that their children also may be depressed and therefore in need of services. J. Am. Acad. Child Adolesc.     

Depression associated with multiple sclerosis: an etiological conundrum

OBJECTIVE: Although depression frequently occurs in multiple sclerosis (MS), an association with cerebral pathology is unclear. This sets MS apart from other common neurological disorders. The reasons for this are explored. METHOD: The literature on depression and magnetic resonance imaging (MRI) is reviewed and methodological issues are critically evaluated. RESULTS: Failure to demonstrate cerebral correlates of depression is in part a function of poor study design. However, the diffuse nature of cerebral demyelination creates difficulties in image analysis peculiar to MS. CONCLUSIONS: More research using valid psychiatric assessment procedures, high field strength MRI and automated lesion detection is needed to resolve the issue. It is premature to reject psychosocial causes at this stage.