Parental Major Depressive Disorder Research Articles

Trait self-acceptance mediates parental childhood abuse predicting depression and anxiety symptoms in adulthood

BackgroundBiopsychosocial models posit that experiencing parental childhood abuse increases vulnerability to psychopathology in adulthood. There are a lack of studies investigating mediators of the parental childhood abuse–adulthood psychopathology relation. The current study investigated if trait self-acceptance mediated the parental childhood abuse–adulthood major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) severity relations. MethodsParticipants (n = 3294) partook in the 18-year Midlife Development in the United States (MIDUS) study at three time-points. We conducted structural equation modeling analyses to test how maternal and paternal childhood abuse at Time 1 would independently positively predict MDD, GAD, and PD severity at Time 3, and if self-acceptance at Time 2 mediated those relations while controlling for adulthood MDD, GAD, and PD severity at Time 1. ResultsSelf-acceptance notably mediated the parental childhood abuse-adulthood MDD, GAD, and PD relations. Overall, higher paternal and maternal childhood abuse was associated with lower self-acceptance. Reduced self-acceptance predicted heightened adulthood MDD, GAD, and PD. ConclusionFindings highlight the importance of understanding the parental childhood abuse–adulthood psychopathology relation and the possible mechanisms of its long-term impact.

Associations Between Parental Mood and Anxiety Psychopathology and Offspring Brain Structure: A Scoping Review.

A family history of mood and anxiety disorders is one of the most well-established risk factors for these disorders in offspring. A family history of these disorders has also been linked to alterations in brain regions involved in cognitive-affective processes broadly, and mood and anxiety disorders specifically. Results from studies of brain structure of children of parents with a history of mood or anxiety disorders (high-risk offspring) have been inconsistent. We followed the PRISMA protocol to conduct a scoping review of the literature linking parental mood and anxiety disorders to offspring brain structure to examine which structures in offspring brains are linked to parental major depressive disorder (MDD), anxiety, or bipolar disorder (BD). Studies included were published in peer-reviewed journals between January 2000 and July 2021. Thirty-nine studies were included. Significant associations between parental BD and offspring caudate volume, inferior frontal gyrus thickness, and anterior cingulate cortex thickness were found. Associations were also identified between parental MDD and offspring amygdala and hippocampal volumes, fusiform thickness, and thickness in temporoparietal regions. Few studies have examined associations between parental anxiety and high-risk offspring brain structure; however, one study found associations between parental anxiety symptoms and offspring amygdala structure, and another found similar associations with the hippocampus. The direction of grey matter change across studies was inconsistent, potentially due to the large age ranges for each study and the non-linear development of the brain. Children of parents with MDD and bipolar disorders, or elevated anxiety symptoms, show alterations in a range of brain regions. Results may further efforts to identify children at high risk for affective disorders and may elucidate whether alterations in specific brain regions represent premorbid markers of risk for mood and anxiety disorders.

Further Evidence that Subsyndromal Manifestations of Depression in Childhood Predict the Subsequent Development of Major Depression: A Replication Study in a 10 Year Longitudinally Assessed Sample

BackgroundWe have previously shown that subsyndromal scores on the Child Behavior Checklist (CBCL)-Anxiety/Depression (Anx/Dep) scale at baseline predicted the subsequent development of Major Depressive Disorder (MDD) in youth with ADHD. The present study aimed to replicate these findings in a separate, long-term, longitudinal sample of children at high- and low- risk for depression. Methods219 children of parents with and without depression and/or anxiety, ages 2-25, were stratified into 3 groups: 1) children with familial risk for depression (by presence of parental MDD) plus subsyndromal scores on the CBCL-Anx/Dep scale, 2) children with familial risk for depression without subsyndromal scores, and 3) children with neither familial risk for depression nor subsyndromal scores. Subjects were reassessed at both 5 and 10 year follow-ups. ResultsChildren with both subsyndromal scores on the CBCL-Anx/Dep plus a familial risk for depression were at greater risk for developing MDD at the 10 year follow-up when compared with all other groups. Those with familial risk but no subsyndromal scores had an intermediate risk that was greater than the controls, who had the lowest risk. LimitationsThe recruitment of the study included families with parental panic disorder, so the sample likely included more families with anxiety disorders than the general population. ConclusionsOur results showed that subsyndromal scores of the CBCL-Anx/Dep scale increased the risk for the subsequent development of MDD, particularly in children at high risk for depression. These results confirm the CBCL-Anx/Dep scale's utility in identifying children at high risk for developing MDD.

Associations Between Depression and Obesity in Parents and Their Late-Adolescent Offspring: A Community-Based Study.

Major depressive disorder (MDD) and obesity are associated within individuals, but little is known about the association between MDD and obesity within families. We hypothesized that parental MDD would predict increased risk for adolescent obesity and that parental obesity would predict increased risk for adolescent MDD. Participants were drawn from the community-based Minnesota Twin Family Study (N = 7307; 17 years old: n = 3774). Parents and their 17-year-old offspring were assessed for MDD using a structured diagnostic interview, and direct assessments of height and weight were conducted (and diagnoses of obesity were derived from these measurements). Parental MDD was associated with offspring obesity (odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.24-2.46). ORs representing the risk associated with maternal and paternal MDD were similar (OR = 1.42, 95% CI = 1.02-1.92; OR = 1.40, 95% CI = 0.88-2.20, respectively). This parental effect remained significant when adjusting for parental obesity and offspring MDD (OR = 1.67, 95% CI = 1.18-2.37). Maternal obesity was associated with increased risk for MDD in offspring (OR = 1.32, 95% CI = 1.06-1.64), but paternal obesity was associated with decreased risk for MDD among offspring (OR = 0.70, 95% CI = 0.54-0.91). These effects remained significant when adjusting for parental MDD and offspring obesity (OR = 1.36, 95% CI = 1.07-1.73; OR = 0.65, CI = 0.49-0.87, respectively). There were no differences in these findings by offspring sex (p values for all tests of a sex interaction term > .374). We found general support for hypothesized cross-disorder associations between MDD and obesity in parents and offspring, suggesting that a shared etiology may underlie these associations. Contrary to prediction, paternal obesity was associated with decreased risk for offspring MDD, a finding that requires further investigation.

Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course?

Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age 11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual single nucleotide polymorphism based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset.

Reducing Major Depression in Children at High Risk: Opportunities for Prevention

The profound negative impact of a parent's Major Depressive Disorder (MDD) on his or her children is of increasing concern to public health and mental health professionals. Children of a depressed parent have a markedly elevated risk for psychiatric illness, including a fourfold increased risk for MDD. The objective is to examine the scientific literature for ways to reduce this high risk to the offspring. First, we consider the relation between effective treatment of a parent's depression and reduced risk to the offspring, and review the effectiveness of treatments for adult M1DD. We then review emerging evidence that risk for psychopathology can be reduced in children of depressed parents by preventive intervention, including targeting two pathways hypothesized as links between parental MDD and offspring psychopathology: parenting skills and child coping. Three 5-year PubMed searches, and a Cochrane Database search, and one Medline and two PsycLit searches (to 1970) were completed (search words in combinations included: depression, prevention, treatments, depression in families, family interaction, adolescents). Randomized controlled studies are included, and review studies and meta-analyses are highlighted to provide a critical overview of the considerable scientific literatures for specific steps that can be taken to reduce the high risk of depression to the offspring of parents with MDD. A deliberate clinical focus on better treatment of MDD in parents is clearly needed and has the potential additional benefit of reducing psychopathology in their children. Altering clinical treatment to address MDD "co-occurring" in both parent and child is supported by the scientific literature. There is also good evidence that preventive intervention with high-risk adolescents reduces the incidence of MDD. Targeting parenting skills and teaching children how to better cope with a parent's illness that they cannot control, appears to reduce MDD in the offspring.

Associations between substance use disorders and major depression in parents and late adolescent–emerging adult offspring: an adoption study

To examine whether major depressive disorder (MDD) and substance use disorders [SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)] in parents predicted increased risk for these disorders in late adolescent-emerging adult offspring and, specifically, the extent to which the pattern of risk differed for adopted and non-adopted youth. Late adolescent and emerging adult participants from the Sibling Interaction and Behavior Study (mean age = 18.8), a community-based investigation of adopted and non-adopted adolescents, and their parents (adoptive parents of adopted youth, biological parents of non-adopted adolescents) were included. Structured interviews were used to assess these disorders. (i) When the same disorder in parents and adolescents was examined, parental MDD was associated with increased risk for MDD among both adopted (P < 0.001) and non-adopted (P < 0.01) adolescents; in contrast, SUDs were associated with increased risk for the same SUD in non-adopted offspring (all P < 0.01). (ii) When cross-SUD effects were examined, for the most part, each SUD was associated with increased risk for other SUDs among non-adopted but not adopted offspring (most P < 0.05). (iii) When MDD-SUD associations were examined, parental ND and CUDs predicted increased risk for MDD in non-adopted (P < 0.001), but not adopted, adolescents. These effects tended to remain significant when adjusting for within-person comorbidity (P < 0.05). Major depressive disorder in parents appears to be a risk factor for late adolescent-emerging adult major depressive disorder but not substance use disorder in offspring, with this risk being environmentally mediated. Substance use disorder in parents appears, via genetic mediation, to increase risk of substance use disorder in adolescent offspring, and cannabis and nicotine use disorders in parents contribute similarly to major depressive disorder in those offspring.

Disruptive behavior disorders in offspring of parents with major depression: Associations with parental behavior disorders

Objective Although the offspring of parents with major depressive disorder (MDD) are at increased risk to develop disruptive behavior disorders (DBD) in addition to MDD, it remains unclear whether this heightened risk is due to MDD or to comorbid DBD in the parents. Method In a secondary analysis of longitudinal data from offspring at risk for MDD and panic disorder and comparison children, we stratified 169 children of parents who had been treated for MDD based upon presence ( n = 50) or absence ( n = 119) of parental history of DBD (ADHD, oppositional disorder, and conduct disorder) and contrasted them with children of parents with DBD but without MDD ( n = 19) and children whose parents had neither MDD nor DBD ( n = 106). The children had been assessed in middle childhood using structured diagnostic interviews. Results Offspring of parents with MDD + DBD had significantly higher rates of MDD, DBD in general, and ADHD in particular, compared with offspring of parents with MDD alone. Offspring of parents with MDD + DBD also had higher rates of mania than controls. Both parental MDD and DBD conferred independent risk for MDD and DBD in the offspring. However, only parental DBD conferred independent risk for conduct disorder and ADHD and only parental MDD conferred independent risk for oppositional defiant disorder. Conclusion Elevated rates of DBD in the offspring of parents with MDD appear to be due in part to the presence of DBD in the parents. Further studies of samples not selected on the basis of parental panic disorder are needed to confirm these results.

The role of fear and anxiety in the familial risk for major depression: a three-generation study

The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression. Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD. In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns. These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.

Influence of Parental and Grandparental Major Depressive Disorder on Behavior Problems in Early Childhood: A Three-Generation Study

This aim of this study was to examine the influence of grandparental (G1) and parental (G2) major depressive disorder (MDD) and other forms of psychopathology on behavior problems in very young offspring (G3). Oregon Adolescent Depression Project (OADP) participants who had children over a 3-year period were invited to participate in a study of infant and child development. We attempted to collect diagnostic history from the original OADP (G2) participants, their coparents, the parents of the original OADP participants (G1), and the parents of the coparents. Child (G3) outcomes at 24 months of age were based on parent reports of behavior problems. Univariate correlations indicated that G1 and G2 familial loadings for MDD were associated with higher levels of G3 internalizing and externalizing behavior problems. Multiple regression analyses revealed a significant interaction between G1 and G2 MDD on G3 internalizing (but not externalizing) behavior problems. A higher familial loading for MDD in either the parental or grandparental generation was associated with elevated grandchild internalizing problems, but higher loadings for MDD in both generations did not convey additional risk. Parental MDD and grandparental MDD are both associated with elevated levels of internalizing problems in young grandchildren, but MDD in both the G1 and G2 generations does not confer additional risk. One important implication is that MDD in the grandparental generation is associated with increased risk to grandchildren even in the absence of parental MDD. Future studies should examine the mechanisms through which grandparental psychopathology influences behavior problems in grandchildren.

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.

Memory deficits in children with and at risk for anxiety disorders

There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders.

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.

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

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. 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). 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. 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.

Families at High and Low Risk for Depression

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. To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. Longitudinal, retrospective cohort, family study. One hundred sixty-one grandchildren and their parents and grandparents. 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. 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. 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.

P.1.088 Temperament and Character Inventory (TCl) in patients with major depressive disorder

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.

Face-memory and emotion: associations with major depression in children and adolescents.

Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. Subjects were 152 offspring (ages 9-19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting 'happy,"fearful,' or 'angry' emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n = 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with MDD.

Onset of Major Depressive Disorder Among Adolescents

To examine the association between parental affective disorders and psychoactive substance use disorders and the onset of major depressive disorder (MDD) among adolescents and young adults and to determine whether this association is affected by stressful life events, family cohesion, self-esteem, or gender. Prospective cohort study of 804 adolescents, aged 11-17 years, and their parents who were followed for seven consecutive years. The sample was drawn from the Minneapolis-St. Paul metropolitan area. Parental diagnoses were based on Structured Clinical Interview for administered during study screening stage. Diagnoses of MDD and age of onset were based on Composite International Diagnostic Interview 2.1 administered during final year of data collection. Of the correlates examined, only parental affective disorders, low self-esteem, and gender were significantly related to the onset of MDD. Females were twice as likely as males to experience MDD. The direct association between parental affective disorders and MDD onset was not affected by family cohesion, self-esteem, or stressful life events; thus more research is needed on other factors that may affect this association, such as genetic factors or other family- and intrapersonal-based variables.

Grandparents, Parents, and Grandchildren at High Risk for Depression: A Three-Generation Study

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. 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. 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. 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.

Offspring at High and Low Risk for Depression and Anxiety: Mechanisms of Psychiatric Disorder

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. 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. 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. 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.