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.     

Cortisol secretion in prepubertal children with major depressive disorder. Episode and recovery

Plasma cortisol concentrations were measured every 20 minutes for 24 hours in a group of 45 rigorously assessed, drug-free, prepubertal children who met the unmodified Research Diagnostic Criteria for major depressive disorder (MDD), 20 children with nonaffective psychiatric disorders, and eight normal controls. All children were studied in a low-stress environment. There were no significant differences in plasma cortisol concentration among the three groups as measured by 24-hour mean, peak, nocturnal rise, or nadir values. Division of the MDD group into subgroups based on endogenicity, psychotic symptoms, and suicidality also failed to reveal significant differences for cortisol secretion. Hypersecretion of cortisol (defined as 2 SDs above the grand mean) was identified in only four children with depressive illness and one normal control. Following clinical recovery, 24 depressed children were restudied in a drug-free state and compared with themselves during the episode of illness and with both groups of controls. No significant differences in plasma cortisol concentrations were found. All four depressed hypersecretors were restudied after clinical recovery, and one showed persistence of hypersecretion. These results suggest that abnormalities of cortisol secretion occur infrequently in prepubertal children with major depression when they are studied in a nonstressful environment.     

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.     

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.     

Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.     

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.     

Suicidal behavior and parental psychopathology in hospitalized depressed children.

This study describes the suicidal behavior of hospitalized depressed children and assesses its relationship to psychopathology and suicidal behavior in their parents. Subjects were 58 consecutively hospitalized prepubertal children with a primary diagnosis of major depressive disorder (MDD), and 58 age- and gender-matched children hospitalized for psychiatric diagnoses other than a mood disorder. Clinical interviews and structured diagnostic instruments were reviewed to determine the children's suicidal behavior and their parents' history of psychopathology. Suicidal ideation, suicidal intent, suicidal plans, and suicide attempts were more frequent in MDD children compared to nondepressed children. When MDD and control samples were stratified as to presence of suicidal behavior in the child, psychopathology was high in parents from all subgroups. Intensity of suicidal behavior in the depressed and non-depressed children was not associated with an altered pattern of psychopathology in their parents. Hospitalized MDD children had increased suicidal behavior compared to inpatient psychiatric control children. However, suicidal behavior in the children was not associated with increased psychopathology or an altered pattern of psychopathology in their parents.     

Blunted stress cortisol reactivity and failure to acclimate to familiar stress in depressed and sub-syndromal children

Depressed adults have shown blunted or elevated cortisol reactivity in response to various forms of psychosocial stress. However, there have been few studies of cortisol reactivity in children who had early onset depression or a history of depression during the preschool–school period. The present study utilized a laboratory stress paradigm and collected salivary cortisol from preschoolers at baseline (ages 3–5 years) and 24-month follow-up (ages 5–7 years). Repeated-measures multivariate analyses of variance (MANOVAs) were used to compare cortisol reactivity to mild stress between children with Major Depressive Disorder (MDD), elevated symptoms of depression (sub-syndromal MDD), and healthy controls. For healthy children, a quadratic cortisol reactivity curve was found at baseline (n=73), which appeared flatter under similar stressful situations at follow-up (n=14), which may reflect acclimation to the paradigm. In contrast, children with MDD (n=46) and sub-syndromal MDD (n=76) showed a peak cortisol response to the novelty of lab arrival and then reduced and blunted responses to stressors at baseline. These cortisol responses persisted at follow-up in children with a history of MDD (n=41) or sub-syndromal MDD (n=73). These results suggest that the hypothalamic–pituitary–adrenal (HPA) axis shows a blunted response to stress and failed to acclimate to familiar stressful situations in depressed and sub-syndromal depressed children.     

Self-assessed parental depressive problems are associated with blunted cortisol responses to a social stress test in daughters. The TRAILS Study

Depression runs in families and is considered a stress-related disorder. Familial risk for depression may be transmitted via deregulated psychophysiological stress responses from parent to child. In this study, we examined the association between self-assessed lifetime parental depressive problems (PDP) and adolescent offspring' cortisol responses to a social stress test. Data were collected as part of the third assessment wave of TRAILS (TRacking Adolescents' Individual Lives Survey), a large prospective population study of Dutch adolescents. Data of 330 adolescents (mean age 16.04; 40.9% girls) who participated in a laboratory session, including a standardized performance-related social stress task (public speaking and mental arithmetic) were examined. Four saliva cortisol samples were collected before, during and after the social stress task which were analyzed with repeated measures Analysis of Variance. Lifetime parental depressive problems were assessed by self-reports from both biological parents. PDP was associated with daughter' cortisol responses (F(3,133)=3.90, p=.02), but no association was found in sons (F(3,193)=0.27, p=.78). Girls whose parents ever experienced depressive symptoms displayed a blunted cortisol response to the standardized social stress test, while girls whose parents never had such problems displayed the characteristic curvilinear response pattern. This effect was not mediated by offspring stress history (age 0-16). Analyses were corrected for smoking behaviour and adolescent depressed mood. The fact that PDP were measured by self-report questionnaires and did not reflect clinical DSM-IV diagnosis could be considered a limitation of the study.     

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.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Depression in recently bereaved prepubertal children

OBJECTIVE: The purpose of this study was to ascertain depressive symptoms in recently bereaved prepubertal children and compare these symptoms with those of depressed prepubertal children. METHOD: The subjects were 38 children who had recently experienced the death of one but not both of their parents. They had to meet strict inclusion criteria so that the effects of bereavement per se, rather than other significant stressors, could be assessed. The comparison group consisted of 38 hospitalized, depressed children individually matched to each bereaved subject for age, sex, and socioeconomic status. All of the children underwent systematic and comprehensive evaluation. They and their parents were independently evaluated by trained interviewers using the parent and child versions of the Diagnostic Interview for Children and Adolescents. Family histories and basic demographic information were also obtained. RESULTS: The recently bereaved children endorsed many depressive symptoms. Thirty-seven percent of them met the DSM-III-R criteria for a major depressive episode. The depressed children, however, had more depressive symptoms on average than the bereaved children. The factors associated with increased depressive symptoms in the bereaved children were 1) the mother as the surviving parent, 2) preexisting untreated psychiatric disorder in the child, 3) family history of depression, and 4) high socioeconomic status. CONCLUSIONS: A considerable number of the bereaved children developed the clinical symptoms of a major depressive episode immediately after the death of a parent. The relation of these symptoms to the subsequent course of grief and to major depressive disorder remains unknown and should be studied further.     

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.     

Similarity in saliva cortisol measures in monozygotic twins and the influence of past major depression.

BACKGROUND: Some studies suggest that cortisol may be under genetic control. The aims of our study were to investigate the familial resemblance in morning and evening cortisol secretion as assessed by saliva cortisol and to assess the influence of history of major depression. METHODS: Women for this investigation were selected from an ongoing study in female-female twin pairs ascertained from the Virginia Twin Registry. Telephone screening assured that current inclusion/exclusion criteria were met. Subjects were asked to collect AM samples within 45 min after awakening, and evening samples immediately before bedtime for 14 days. RESULTS: There was a high degree of correlation across weeks in both the AM and PM cortisol values, indicating significant stability across individuals. There was significant correlation between AM and PM cortisol in monozygotic twins. In twins with a history of major depression (n = 30), compared with the twins without past major depression (n = 28), there was a trend towards higher cortisol (p = .056). CONCLUSIONS: These results suggest that around 40-45% of the total variance in salivary cortisol is shared by monozygotic twins. Although the increase in baseline cortisol in twins with a history of major depression is only significant at the trend level, the effect size is comparable to an "in episode" depressed population.     

Physical health problems in depressed and nondepressed children and adolescents of parents with opiate dependence

The increased risk of physical health problems in adult depressed patients has been shown in numerous studies. A recent study of the offspring of depressed parents found similar associations. The purpose of this study is to examine the strength and specificity of the association between depression and physical health problems in children and adolescents whose parents are dependent upon opiates. The sample consisted of offspring ages 6-17 (mean age 11 years) of opiate addicts who had a history of major depressive disorder (MDD; n = 28); other mood disorders (n = 31); no history of mood disorders but other psychiatric disorders (n = 92); or no history of psychiatric disorder (n = 127). Detailed psychiatric assessment and medical history of the offspring by direct interview with the offspring and an informant were obtained blind to parental diagnosis. After controlling for possible confounders, there was an increased risk of dermatological disorders, headache, other neurological/neuromuscular disorders, bronchitis, other respiratory disorders and hospitalizations for nonsurgical procedures in offspring with MDD, as compared to nonpsychiatrically ill controls. The offspring with other mood disorders had a slightly elevated risk. Major depression in children and adolescents whose parents are dependent on opiates is associated with increased risk of physical health problems. This finding is consistent with other reports and the timing of the physical health problems requires further study.     

Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder

OBJECTIVE: To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N=52) with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N=10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. METHOD: Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day. RESULTS: PTSD was associated with enhanced cortisol suppression in response to DEX. Among trauma survivors, the presence of a traumatic event prior to the "focal" trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. CONCLUSIONS: Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. However, prior trauma exposure may affect cortisol suppression in MDD. This finding may have implications for understanding why only some depressed patients show non-suppression on the DST.     

Evaluation of a focused short-term preventive counselling project for families with a parent with cancer

Twenty-four families participated in counselling for families with a parent with cancer (24 mothers, 17 fathers, and 34 children). Parents who received counselling were significantly more depressed before the counselling than a nonrandomized control group who did not receive counselling, but participated in another part of the project. For the parents, there was a significant decrease in depression and increase in family functioning scores from before to after the intervention. For the children, a significant pre- to post-decrease in depression scores was found. Changes in depression and family functioning were significantly correlated with the degree of counselling contentment. Reasons for seeking counselling were insecurity in relation to the children, problems with communication, high level of conflict, and change of roles. A number of themes appeared when parents and children described what they gained from the counselling: Confirmation in being a 'good-enough' parent, more understanding of emotions and reactions of other family members, more sense of intimacy and cohesion within the family, and normalization of own feelings.     

The dexamethasone suppression test in children and adolescents: a review and a controlled study.

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.     

The dexamethasone suppression test in prepubertal depressed children

The dexamethasone suppression test (DST) was performed in 50 hospitalized prepubertal children who met DSM-III criteria for major depressive episode, 18 hospitalized controls with a psychiatric disorder, and 18 nonhospitalized normal controls. Baseline and post-DST cortisol levels were measured at 8 a.m. and 4 p.m. The depressed children had consistently higher cortisol levels than the controls at baseline and post-DST. The DST was positive in 82% of depressed children, 28% of psychiatric controls, and 11% of normal controls. The results indicate that prepubertal depressed children may have abnormalities in the hypothalamic-pituitary-adrenal axis similar to those in adults with a major depressive illness.     

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.