Families at high and low risk for depression: a three-generation startle study.

BACKGROUND: Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD). Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. METHODS: The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation). RESULTS: Startle discriminated between the low- and high-risk groups. In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. CONCLUSIONS: Increased startle reactivity in threatening contexts, previously found in patients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD. These findings suggest that there might be common biologic diatheses underlying depression and anxiety.     

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.     

First episode of depression in children at low and high familial risk for depression

OBJECTIVE: To examine the development of first-onset major depressive disorder (MDD) in children at high and low familial risk for depression in a prospective study. METHOD: High-risk children (n = 76) who were free of any lifetime affective disorder and had at least one first-degree and one second-degree relative with a lifetime history of childhood-onset, recurrent, bipolar, or psychotic depression were included. Low-risk children (n = 63) were included if they were free of any lifetime psychiatric disorder and had no first-degree relatives and fewer than 20% of their second-degree relatives with a lifetime affective disorder. Children and their parents were assessed in a prospective design using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version (K-SADS-E). The average interval between follow-up interviews was 18 months, and the average follow-up period was 6 years. RESULTS: High-risk children had approximately a threefold increased risk of developing first-onset MDD compared with low-risk children (odds ratio = 3.21). The average age of new-onset MDD was 14.0 +/- 2.9 years (range 9.5-19.5 years). Above and beyond the familial loading for MDD, mother's lifetime anxiety disorder (odds ratio = 2.84) and lifetime behavioral disorder (odds ratio = 3.25) in the child significantly added to the risk of developing a first-onset MDD. CONCLUSIONS: Having high familial loading for affective disorders, a mother with and anxiety disorder, and a behavioral disorder in the child all significantly contributed to the risk of developing 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.     

Mother-child interactions in depressed children and children at high risk and low risk for future depression

ObjectiveTo compare mother-child interactions and parenting styles in families of children with major depressive disorder, youths at high risk for depression, and healthy controls.MethodCurrently depressed (n = 43), high-risk (n = 28), and healthy control (n = 41) youths and their mothers engaged in a standardized videotaped problem-solving interaction. Measures of affect and behavior for both mothers and children were obtained, in addition to global measures of parenting.ResultsDepressed children demonstrated more negativity and less positivity in dyadic interactions than did children at high risk and control children. Mothers of depressed children were more disengaged than control mothers. Exploratory repeated-measures analyses in a subgroup of depressed children (n = 16) suggested mother-child interactions do not significantly change when children recover from depression. Children at high risk demonstrated less positivity in dyadic interactions than did controls. Mothers with a history of major depressive disorder and mothers with higher current depressive symptoms demonstrated patterns of disengagement and low control in interactions with children.ConclusionsMother-child interactions in depressed youths are marked by maternal disengagement and low child positivity that may not improve when children recover. The bidirectional effects of maternal disengagement and low levels of child positivity may precede onset of major depressive disorder in children and serve as risk factors for recurrent depression in youths.     

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.     

Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study.

BACKGROUND: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness. METHODS: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence. RESULTS: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence. CONCLUSIONS: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.     

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.     

Electrophysiological and microstructural features of sleep in children at high risk for depression: a preliminary study

ObjectiveThis preliminary study investigated electrophysiological and microstructural features of sleep in children and adolescents 4–18 years of age who were born to depressed mothers.MethodsA total of 31 healthy subjects (15 male and 16 female) participated in the study. In this sample, 20 children born to mothers diagnosed with Major Depressive Disorder (MDD) were designated as “high-risk”; 11 children born to mothers without a personal history of depression were designated as “low-risk.” Polysomnography including three-channel electroencephalography (EEG) was recorded for one night at the Pediatric Sleep Unit of the University Hospital of Lyon, France. Clinical and demographic data were collected. Sleep architectural parameters were analyzed. Sleep microstructure was assessed with the scoring of cyclic alternating pattern (CAP) and CAP measures were calculated. Spectral analysis was performed, and mean EEG band power was computed for each sleep stage. Sleep electrophysiological features (slow waves and sleep spindles) were detected, and related parameters were analyzed. Data were compared between high- and low-risk groups using Student t tests.ResultsA reduction in low-frequency spindle activity and slow spindles spatio-temporal characteristics over frontal and central derivations, and an altered distribution of CAP phase A subtypes (reduction of A1 over A2–3 ratio) were observed in the high-risk group relative to the low-risk group.ConclusionLimited spindles generation and increased non-rapid eye movement sleep instability, observed in children born to depressed mothers, might reflect functional anomalies in cortical plasticity that could represent a pathogenic factor or an epiphenomenon for MDD.     

Panic disorder in children at high risk for depression

While conventional clinical wisdom has been that panic disorder does not occur in children, evidence derived from structured diagnostic interviews suggests that panic disorder, similar in symptom pattern to the adult disorder, does occur in children and can occur before puberty.     

Relationship of resting EEG with anatomical MRI measures in individuals at high and low risk for depression

Studies have found abnormalities of resting EEG measures of hemispheric activity in depressive disorders. Similar EEG findings and a prominent thinning of the cortical mantle have been reported for persons at risk for depression. The correspondence between EEG alpha power and magnetic resonance imaging (MRI) measures of cortical thickness was examined in a multigenerational study of individuals at risk for depression. Seventy-five participants underwent resting EEG and approximately 5 years later underwent MRI scanning. High-risk participants (n = 37) were biological descendants of probands having major depression and low-risk participants (n = 38) were descendants of individuals without a history of depression. EEG alpha power was interpolated across the surface of a template brain and coregistered with measures of cortical thickness. Voxel-wise correlations of cortical thickness and alpha power were computed while covarying for age and gender. The high-risk group, when compared to the low-risk group, showed greater alpha asymmetry in an eyes-closed condition, with relatively less activity over right parietal cortex. Alpha power correlated inversely with cortical thickness, particularly over the right posterior region, indicating that EEG evidence of reduced cortical activity was associated with increased cortical thinning. This is the first report of widespread correlation of EEG alpha activity with MRI measures of cortical thickness. Although both EEG and MRI measures are associated with risk for depression, we did not detect evidence that cortical thickness mediated the alpha asymmetry findings. Thus, alpha asymmetry, alone or in combination with MRI, may be a marker of vulnerability for a familial form of depression.     

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.     

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:     

Cognition and nondysphoric depression among adoptees at high risk for psychopathology

Background

Association between poor cognition and symptom clusters including depressive ideation (eg, guilt) and vegetative symptoms in the absence of dysphoria (nondysphoric depression [NDD]) has been suggested in the elderly. The current study examined associations between NDD and premorbid and concurrent cognitive functioning in younger adults at high risk for psychopathology. Nondysphoric depression and depressed subjects were expected to show poorer premorbid and current cognition than nondepressed participants.

Method

Subjects were adoptees enrolled in the Iowa Adoption Study [Yates W, Cadoret R, Troughton E. The Iowa adoption studies: methods and results. On the way to individuality: methodological issues in behavioral genetics. In: LaBuda M, Grigorenko E, (Eds), Editor. 1999, Commack (NY): Nova Science Publishers, Inc. p. 95-121]. Nondysphoric depression subjects were compared with nondepressed comparison subjects and with subjects with dysphoric depression (DD) on measures of premorbid cognition (estimated by standardized school achievement test scores) and concurrent cognition (intelligence, attention, memory, and executive abilities).

Results

Nondysphoric depression and DD showed lower premorbid cognition and executive functioning, whereas DD showed lower verbal and performance IQ compared to nondepressed subjects. The size of the comparison between NDD and nondepressed subjects for premorbid cognition was double that between DD and nondepressed subjects. No significant differences in cognition were found between NDD and DD. These effects were no longer significant after controlling for premorbid cognition.

Conclusions

Poorer premorbid cognition and executive functions in NDD (and the absence of current cognitive differences compared with DD) suggest that NDD may be a condition of clinical interest. Because poor cognition is a known correlate of alexithymia, these results (including their magnitude) are consistent with the view that NDD may be a paradoxical presentation of depression in persons with limited ability to be aware and to verbally-report emotions.     

Social media use predicts later sleep timing and greater sleep variability: An ecological momentary assessment study of youth at high and low familial risk for depression

IntroductionSocial media (SM) use has been increasingly recognized as a potential contributor to poor sleep. Few studies have examined SM use and sleep using ecological momentary assessment (EMA), compared different types of media use (SM, television, gaming), or examined whether youth at high and low familial risk for depression are differentially affected by SM use.MethodsThe current study included 76 youth (46% female; Mean age = 11.28 years) who were recruited based on parental history of recurrent depression (N = 35 high risk; N = 41 low risk) in the United States. Youth completed a 9-day EMA protocol, which included current activity at time of prompt and daily sleep onset and offset times. Regression and multilevel models were conducted to examine the effects of media use on sleep.ResultsResults indicated that youth who used more SM (mean and number of days) went to sleep later, but did not have shorter sleep duration. Youth with more SM use also had higher levels of variability of both sleep timing and sleep duration across the 9-day period. There were no effects of gaming or TV on sleep, and youth at high risk for depression did not have differences in SM use or its effects on sleep compared to low-risk youth.ConclusionsThese findings indicate a unique impact of SM use on sleep timing and variability for youth (regardless of risk status), which may suggest a unique and modifiable pathway through which SM use contributes to poor health.     

Reduced cortical folding in individuals at high risk for schizophrenia: a pilot study

While cortical gyrification anomalies have been reported in schizophrenia, it is unknown if individuals at high risk for schizophrenia (HR) might also exhibit abnormal cortical folding. Using MRI scans, the gyrification index (GI) was calculated for 9 adolescent HR males and 12 healthy male controls. Using the first coronal slice anterior to the corpus callosum, cortical contours were manually traced to calculate the GI. The left GI was lower in HR when compared to controls, but no difference in the right GI was observed. These results are consistent with studies of affected individuals, supporting genetic and neurodevelopmental models of schizophrenia.     

Two-year recall of lifetime diagnoses in offspring at high and low risk for major depression. The stability of offspring reports

Stability of recall of DSM-III diagnoses was assessed at two interviews 2 years apart in a sample of 150 offspring, aged 6 to 23 years, at high and low risk for major depression. Stability of recall was good for major depression with the use of DSM-III criteria and fair for major depression with the use of "strict" criteria (based on 4 weeks' duration of illness and an impairment in a major social role). Stability of recall was good for substance abuse and conduct disorder. Stability of recall was generally poor for anxiety disorder, regardless of subtype. For all major disorders except anxiety disorder, the difference in reported age at onset between the two interviews was small (less than 1 year) and not statistically significant. The most important correlates of stability of reports of major depression were previous psychiatric treatment and dysthymia and poor social functioning at the initial interview. This is the first study to evaluate long-term recall of DSM-III lifetime diagnoses in a nonreferred sample of children, adolescents, and young adults.     

Family functioning in adolescents at high and low risk for major depressive disorder

Families of two subgroups of adolescents in the community, at high and low risk for major depressive disorder, were compared on the McMaster Family Assessment Device (FAD) and the General Health Questionnaire (GHQ). Families of high-risk adolescents who became depressed by follow-up at one year were comared with other families of high-risk subjects. The only significant difference on FAD ratings for high- and low-risk groups was on the sub-scale Roles as reported by mothers. FAD ratings showed that, compared with mothers, fathers of high-risk adolescents held significantly worse views of their families' functioning on the sub-scales Problem Solving. Affective Responsiveness and Behaviour Control. There were no such differences between low-risk parents. Both mothers and fathers of high-risk adolescents reported their own mental health as significantly poorer than mothers and fathers of low-risks. The mental health of mothers in the high-risk group only was significantly associated with their FAD ratings. Adolescents rated their families as significantly worse on the FAD than their parents and the lower their mood and self-esteem, the worse they rated their families on the FAD. Subsequent MDD in adolescents by follow-up at one year was not associated with the FAD scores of any family member, nor with either parent's mental health. Accepted: 26 January 2001