Families at high and low risk for depression: a 3-generation study

BACKGROUND: The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort. OBJECTIVE: To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. DESIGN: Longitudinal, retrospective cohort, family study. PARTICIPANTS: One hundred sixty-one grandchildren and their parents and grandparents. MAIN OUTCOME MEASURES: Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews. RESULTS: There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression. CONCLUSIONS: The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.     

A high risk study of young children of parents with panic disorder and agoraphobia with and without comorbid major depression

Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders.     

Grandchildren at high and low risk for depression differ in EEG measures of regional brain asymmetry.

BACKGROUND: Electrophysiologic studies have found abnormalities of alpha asymmetry in depressed adults and offspring of depressed parents, which have been hypothesized to be vulnerability markers of depression. Resting electroencephalogram (EEG) was measured in grandchildren participating in a multigenerational high-risk study. METHODS: Electroencephalogram from 12 electrodes at six homologous sites over each hemisphere (digitally linked-ears reference) was compared in right-handed grandchildren in three groups: 1) both parent and grandparent having major depressive disorder (MDD; n = 19); 2) either parent or grandparent having MDD (n = 14); and 3) neither having MDD (n = 16). RESULTS: Grandchildren with both depressed parent and grandparent showed greater alpha asymmetry, with relatively less right than left hemisphere activity, when compared with those with neither depressed parent nor grandparent. This difference was present over the parietal region in the eyes-closed condition. Grandchildren having either depressed parent or grandparent also tended to show heightened alpha asymmetry at parietal sites, but they did not differ significantly from those with neither depressed parent nor grandparent. Low-risk grandchildren with neither depressed parent nor grandparent showed no significant alpha asymmetry. CONCLUSIONS: High-risk grandchildren displayed a parietal alpha asymmetry similar to that seen in adolescents or adults having a MDD and in second-generation offspring of parents concordant for MDD. Its presence in high-risk offspring and grandchildren without a lifetime history of MDD supports the hypothesis that an alpha asymmetry indicative of relatively less right than left parietal activity is an endophenotypic marker of vulnerability to a familial form of major depression.     

Temperament among offspring at high and low risk for depression

The purpose of this study was to examine relationships between parental depression, offspring temperament, and offspring major depressive disorder (MDD), and to determine whether difficult temperament, as measured by the Dimensions of Temperament Survey (DOTS), mediates the relation between parental MDD and offspring MDD. Offspring (n=169) of depressed or never depressed parents were followed over approximately 20 years and were blindly assessed up to 4 times (Waves 1 to 4) using semi-structured interviews. Offspring completed the DOTS at the time of first or second assessment. The results showed: (1) high-risk offspring with one or more depressed parent were significantly more likely than offspring with neither parent depressed to have a difficult temperament; (2) offspring with a difficult temperament were more than twice as likely as those with an easy temperament to develop a MDD; and (3) difficult temperament explained more than 10% of the association between parental depression and new onsets of MDD in offspring. The findings suggest that offspring temperament is associated with development of MDD and that difficult temperament at least partially mediates the relationship between parental depression and offspring depression. When identifying those at greatest risk for MDD, measures of temperament could serve as a useful supplement to family psychiatric history of MDD.     

Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression

Numerous studies have demonstrated that low birth weight (LBW) is associated with the development of medical conditions, such as hypertension and diabetes, and psychiatric disorders, such as depression. One possible mechanism through which LBW might increase risk for both medical and psychiatric disorders is by altering the biologic systems (such as the hypothalamic-pituitary-adrenal [HPA] axis function) that govern emotion regulation and physical reactivity. In this study, we conducted secondary data analyses in a longitudinal study originally designed to understand the intergenerational transmission of major depressive disorder (MDD). We examined the risk for both medical and psychiatric illnesses known to be influenced by HPA axis dysregulation in the context of parental depression. The study had 2 primary objectives: (1) to examine whether LBW increases the risk of selected adult illness that may be influenced by the HPA axis and (2) to examine whether the increased risk of illness varies by parental depression status. We conducted longitudinal assessments of 244 offspring of depressed and nondepressed parents for more than 20 years. Psychopathology and medical illness were assessed by direct interview conducted by clinicians blind to risk status and previous diagnosis. We examined the effect of BW in 3 categories: less than 2.5 kg (LBW), 2.5-3.5 kg, and more than 3.5 kg (reference group). Offspring with LBW had a significantly increased risk of MDD, anxiety disorders, phobia, suicidal ideation, impaired functioning, allergies, and hypertension compared to those with BW exceeding 3.5 kg. The association between LBW and depression was stronger among children of depressed parents than among children of nondepressed parents, with an interaction term (BW and parental depression status) significant for MDD (P = .05), suggesting that parental depression may augment the impact of LBW on offspring depression:     

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study

OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. METHOD: Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. RESULTS: Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.     

Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders.

BACKGROUND: Electroencephalographic (EEG) studies have found abnormal regional hemispheric asymmetries in depressive disorders, which have been hypothesized to be vulnerability markers for depression. In a longitudinal high-risk study, resting EEG was measured in primarily adult offspring of depressed or nondepressed probands. METHODS: Electroencephalograms from12 homologous sites over each hemisphere (digitally linked-ears reference) were analyzed in right-handed offspring for whom both parents (n = 18), one parent (n = 40), or neither parent (n = 29) had a major depressive disorder (MDD). RESULTS: Offspring with both parents having MDD showed greater alpha asymmetry at medial sites, with relatively less activity (more alpha) over right central and parietal regions, compared with offspring having one or no parent with MDD. Relatively less left frontal activity at lateral sites was associated with lifetime MDD in offspring but not with parental MDD. Offspring with both parents having a MDD also showed markedly greater anterior-to- posterior increase in alpha with eyes closed compared with those with one or no parent with a MDD. CONCLUSIONS: Alpha asymmetry indicative of right parietotemporal hypoactivity, previously reported for depressed adolescents and adults, and heightened anterior-to-posterior gradient of alpha are present in high-risk offspring having parents concordant for MDD.     

Anxiety and depressive disorders in offspring at high risk for anxiety: A meta-analysis

This paper presents a meta-analysis of studies examining prevalence of psychopathology among offspring of anxiety-disordered parents, with the purpose of determining overall risk among these offspring for developing anxiety and depressive disorders. Pooled odds ratios for these disorders among high-risk offspring, compared to offspring of psychiatric and non-psychiatric controls, were calculated. Sixteen papers (including three follow-up studies) were identified, encompassing 1892 offspring (ages 4–25 years). Results revealed that: (1) offspring of parents with anxiety disorders have greater risk for anxiety and depressive disorders than offspring of non-psychiatric controls (ORs = 3.91 and 2.67, respectively) and greater risk for anxiety disorders than offspring of psychiatric controls (OR = 1.84); (2) offspring of anxious parents have significantly greater odds of having each type of anxiety disorder and MDD compared to offspring of non-psychiatric controls (ORs range from 1.96 to 8.69); and (3) offspring of parents with anxiety only, anxiety plus MDD, and MDD only have similar odds of having anxiety and depressive disorders but significantly higher odds than offspring of parents without disorder. Results suggest that parental anxiety disorders confer significant risk for anxiety and depression in offspring. Additional studies are needed to examine whether there are differences among specific parental anxiety disorders.     

Psychopathology in the young offspring of parents with bipolar disorder: a controlled pilot study

Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a pre-existing sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n=34), of parents with panic or major depression (n=179), and of parents with neither mood or anxiety disorder (n=95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood.     

Psychiatric phenomenology of child and adolescent bipolar offspring

OBJECTIVE: To establish prodromal signs of and risk factors for childhood bipolar disorder (BD) by characterizing youths at high risk for BD. METHOD: Structured diagnostic interviews were performed on 60 biological offspring of at least one parent with BD. Demographics, family histories, and parental history of childhood disruptive behavioral disorders were also assessed. RESULTS: Fifty-one percent of bipolar offspring had a psychiatric disorder, most commonly attention-deficit/hyperactivity disorder (ADHD), major depression or dysthymia, and BD. BD in offspring tended to be associated with earlier parental symptom onset when compared with offspring without a psychiatric diagnosis. Bipolar parents with a history of childhood ADHD were more likely to have children with BD, but not ADHD. Offspring with bilineal risk had increased severity of depressed and irritable mood, lack of mood reactivity, and rejection sensitivity, while severity of grandiosity, euphoric mood, and decreased need for sleep were not preferentially associated with such offspring. CONCLUSIONS: Bipolar offspring have high levels of psychopathology. Parental history of early-onset BD and/or childhood ADHD may increase the risk that their offspring will develop BD. Prodromal symptoms of childhood BD may include more subtle presentations of mood regulation difficulties and less presence of classic manic symptoms.     

Parent-child bonding and family functioning in depressed children and children at high risk and low risk for future depression

OBJECTIVE: To evaluate parent-child bonding and familial functioning in depressed children, children at high risk for depression, and low-risk controls. METHOD: Diagnoses of children and their relatives were obtained via structured interviews with all available informants. Depressed children (n = 54) received a diagnosis of current major depressive disorder (MDD). The high-risk children (n = 21) had no lifetime diagnoses of mood disorders, but at least one first-degree relative with a lifetime history of depression. The low-risk controls (n = 23) had no lifetime psychiatric disorders and no first-degree relative with a lifetime history of mood disorders. Parent-child bonding was evaluated with the child's report on the Parental Bonding Instrument (PBI). Familial functioning was evaluated with each parent answering the Family Assessment Device (FAD). RESULTS: Significant differences were found between the MDD and low-risk children on most parameters of the PBI and FAD. The children with MDD reported significantly elevated maternal overprotection, and their fathers scored significantly lower on the FAD scales of Behavioral Control and General Functioning, compared with the high-risk children. Mothers of high-risk children had significantly lower scores on the Roles and Affective Involvement dimensions of the FAD compared with mothers of low-risk children. Current maternal depression had a deleterious effect on the child's perception of maternal protection and paternal care, mother's report on all FAD scales, and father's report on most FAD scales, whether interacting with the child's depression or existing even if the child was not depressed. CONCLUSION: Maternal depression and its interaction with the child's depression appear to have negative consequences for parent-child bonding and family functioning.     

Depressive disorders in childhood. IV. A longitudinal study of comorbidity with and risk for anxiety disorders

As part of a longitudinal nosologic study of major depressive disorder (MDD), dysthymic disorder (DD), and adjustment disorder with depressed mood (ADDM) in a school-age cohort, we examined the prevalence and clinical consequences of comorbid anxiety disorders. We also estimated the risk of a first anxiety disorder and examined its predictors. Of 104 cases, 41% had anxiety disorders in conjunction with their index depression, which was more likely with MDD and DD than with ADDM. The age-corrected risk of a first anxiety disorder was 0.47 up to age 18 years. Separation-anxiety disorder was the most frequent diagnosis of anxiety, followed by overanxious disorder of childhood. Among the MDD cases with comorbidity, the anxiety disorder preceded the depression about two thirds of the time and often persisted after the depression remitted. The effect of comorbid anxiety disorder on the length of index MDD depended on the presence of other clinical features, but it did not seem to affect the risk of subsequent MDD or the course of DD or ADDM. Concurrent maternal psychopathology and poor physical health increased the risk of anxiety disorder in the children, but a history of prior separation from parental figures did not seem to have an effect.     

Early-onset depression and the emotional and behavioral characteristics of offspring

We compared the emotional and behavioral characteristics of offspring of parents with early-onset depression and the offspring of parents with late-onset depression. Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist-Parent Report Version (CBCL) for a birth child (n=43, age range 6-17 years). Parents were classified as having either early SD onset (<19 years) or late-onset (> or = 19 years) MDD based on responses gathered during the SCID-P interview. Unpaired t-tests were used to compare the two offspring groups on CBCL clinical and competency scales. Chi-square analyses and unpaired t-tests were used to compare the two parent groups on demographic and clinical features. Offspring of parents with early-onset depression scored significantly higher on the majority of the CBCL clinical scale scores when compared with offspring of parents with late-onset depression, rated as exhibiting higher levels of the characteristics measured: withdrawn, anxious/depressed, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior. Additionally, this group had a significantly higher total T score (a global measure of psychopathology) and significantly lower social functioning. Children of parents with early-onset depression may be at higher risk for behavioral and emotional problems than offspring of parents with late-onset depression. This finding may be significant in uncovering sources of vulnerability and formulating intervention strategies for offspring of depressed parents.     

Dependency and self-criticism: relationship with major depressive disorder, severity of depression, and clinical presentation

Dependency and self-criticism have been proposed as personality dimensions that confer vulnerability to depression. In this study we set out to investigate the diagnostic specificity of these personality dimensions and their relationship with gender differences, severity of depression, and specific depressive symptoms. Levels of dependency and self-criticism as measured by the Depressive Experiences Questionnaire (DEQ) were compared among patients with major depressive disorder (MDD; n=93), mixed psychiatric patients (n=43), university students (n=501), and community adults (n=253). Associations with severity of depression and specific depressive symptoms were also explored. Results showed that dependency was more specifically associated with MDD, whereas self-criticism did not differ between depressed and mixed psychiatric patients. In line with the gender incongruence hypothesis, women with MDD and other psychiatric disorders had higher levels of self-criticism compared to men, whereas men with MDD had higher levels of dependency compared to women. Severity of depression was more clearly linked to self-criticism than to dependency, particularly in patients with MDD. Finally, both dependency and self-criticism were related to theoretically predicted clusters of depressive symptoms, especially after we controlled for shared variance between self-critical and dependent symptoms, respectively. Limitations of this study include the cross-sectional design, which limited the ability to draw causal conclusions. In addition, this study relied exclusively on self-reported personality and mood. Overall, findings of this study suggest that both dependency and self-criticism are associated with MDD, severity of depression, and specific depressive symptoms, and that gender-incongruent personality traits may be associated with increased risk for depression and other disorders.     

The influence of lifetime depression on self-reported memory and cognitive problems: results from the National Comorbidity Survey-Replication

The current study investigated the association between lifetime major depressive disorder (MDD) and self-reported memory and cognitive problems in a general population sample. The study was based on data from the National Comorbidity Survey-Replication (n = 5692). The relationship between lifetime MDD and self-reported memory and cognitive problems was examined while controlling for other 1-year and lifetime psychiatric disorders. We found a lifetime history of depression, but no other lifetime psychiatric disorder, to be associated with self-reported memory and cognitive problems. We review the results in relation to theories regarding the comorbidity of depression and cognitive problems. A history of depression increases the likelihood that individuals will make negative evaluations of their memory and cognitive functioning. Though depression is highly comorbid with other disorders, our results are unique in demonstrating the specificity of depression in its association with self-reported memory and cognitive problems. The observed association between depression and self-reported memory and cognitive problems may reflect that depression increases the risk for cognitive decline or may reflect that individuals with a history of depression tend to rate their memory as poor, or both.     

Adolescent outpatients with depressive disorders: clinical characteristics and treatment received

Depressive disorders constitute a common clinical problem. However, research on psychosocial impairment and treatment-related factors among adolescent outpatients with different diagnoses of depression is scarce. This study aimed at investigating consecutively referred outpatient adolescents with depressive syndrome compared with psychiatric controls. We also compared those with major depression (MDD), other depressive disorders (OD), or adjustment disorder with depressed mood (ADDM) in terms of psychosocial impairment and treatment received in a sample of 302 consecutively referred adolescent outpatients. Psychosocial impairment was most severe in MDD. Comorbidity with anxiety disorders characterized those with MDD, whereas antisocial disorders were common among those with OD. Psychosocial treatment was more intensive and psychotropic medication more prevalent in patients with MDD compared with those with OD or ADDM. All the depressed patients receiving psychotropic medication had additional psychosocial treatments. Psychosocial functioning improved in all three groups (MDD, OD, ADDM), whether their treatment involved only psychotherapeutic treatments or additional psychotropic medication. Adolescents with different diagnoses of depression have specific psychosocial impairments that have to be taken into account in developing psychiatric treatments for them.     

Clinical characteristics of depressive symptoms in children and adolescents with major depressive disorder

OBJECTIVE: Very few studies have compared the symptoms of major depressive disorder (MDD) and rates of comorbid psychiatric disorders between depressed children and adolescents. The aim of this study was to reproduce and extend these findings. METHOD: The Kiddie Schedule for Affective Disorders and Schizophrenia, present version (KSADS-P) was administered to parents (about their children) and in face-to-face interviews with 916 subjects aged 5.6 to 17.9 years with MDD (DSM criteria) (715 adolescents and 201 children; 348 male and 568 female). The subjects were consecutive referrals to an outpatient mood and anxiety disorders clinic. RESULTS: Depressed adolescents had significantly more hopelessness/helplessness, lack of energy/tiredness, hypersomnia, weight loss, and suicidality compared with children (p values < or = .001). In comparison with children, adolescents had significantly more substance abuse and less comorbid separation anxiety disorder and attention-deficit/hyperactivity disorder (p values < or = .001). Depressed female adolescents had significantly more suicidality than depressed male adolescents (p < or = .001). There were no other sex differences between males and females. The symptoms of depressed adolescents grouped into 3 factors (endogenous, negative cognitions/suicidality, and appetite/weight), whereas the symptoms in children grouped into 2 factors (endogenous/negative cognitions/suicidality and appetite/weight). CONCLUSIONS: These results provide further evidence for the continuity of MDD from childhood to adolescence.     

Incidence of psychiatric disorder in offspring at high and low risk for depression.

First onsets (incidence) of suicide attempts and DSM-III psychiatric disorders, including major depression, any anxiety disorder, conduct disorder, or substance abuse were determined in a 2-year longitudinal study of 174 offspring at high and low risk for major depression. All of the suicide attempts, the first onsets of major depression, and anxiety disorders were in offspring of depressed parents. Compared with asymptomatic offspring, offspring with subclinical manifestations of major depression, conduct disorder, and substance abuse at the initial interview were significantly more likely to become incident cases of the same disorder over the next 2 years. Either conduct disorder or substance abuse at initial interview were highly predictive of first onset of each other, but not of any other disorders 2 years later. Family risk factors (such as poor marital adjustment, parent-child discord, low cohesion, and affectionless control) at initial interview were associated with increased incidence of substance abuse, or conduct disorder, but not major depression or anxiety disorder. Combining both retrospective and prospective data, the overall suicide attempt rate was 7.8% in the offspring of depressed parents as compared with 1.4% in the offspring of nondepressed parents. By age 20, over 50% of the offspring of depressed patients reported a major depression.     

Psychopathology in the offspring of parents with bipolar disorder: a controlled study.

BACKGROUND: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. METHODS: Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. RESULTS: Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. CONCLUSIONS: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.     

Mental disorders in offspring of parents with bipolar and major depressive disorders

Vandeleur C, Rothen S, Gholam‐Rezaee M, Castelao E, Vidal S, Favre S, Ferrero F, Halfon O, Fumeaux P, Merikangas KR, Aubry J‐M, Burstein M, Preisig M. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 2012: 14: 641–653. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. Methods: A total of 376 offspring (aged 6.0–17.9 years; mean = 11.5 years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co‐parents were interviewed by psychologists blind to proband diagnoses, using a semi‐structured diagnostic interview. Results: Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). Conclusions: These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.