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.     

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.     

Event centrality and secondary traumatization among Holocaust survivors' offspring and grandchildren: A three-generation study

The present study examined the intergenerational transmission of the Holocaust trauma in relation to levels of secondary traumatization and event centrality across three generations in a cross-sectional survey. Participants included 92 Holocaust survivor-offspring-grandchild triads (Holocaust G1-G2-G3) and 67 comparison triads (Comparison G1-G2-G3). Holocaust G1 reported higher levels of post-traumatic stress disorder (PTSD) symptoms relative to Comparison G1. Holocaust G2 and G3 reported significantly higher secondary traumatization relative to Comparison G2 and G3, respectively. Holocaust G3 also reported significantly higher scores in event centrality relative to Comparison G3. In survivor families, the indirect effect of PTSD symptoms in Holocaust G1 predicted Holocaust G2's secondary traumatization, which subsequently predicted Holocaust G3's secondary traumatization. Moreover, PTSD symptoms in Holocaust G1 predicted Holocaust G3's event centrality through secondary traumatization in both Holocaust G2 and G3 and event centrality in Holocaust G2. In the comparison groups, trauma transmission was not observed in three generations. Findings elucidate unique intergenerational transmission of the Holocaust trauma in survivor families, which comprise both personal and societal constituents. Moreover, the findings show that event centrality is a distinctive mechanism in intergenerational transmission in survivor families.     

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.     

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.     

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.     

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.     

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.     

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.     

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

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

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.     

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.     

Adverse childhood experiences,alcoholic parents,and later risk of alcoholism and depression

OBJECTIVE: The study examined how growing up with alcoholic parents and having adverse childhood experiences are related to the risk of alcoholism and depression in adulthood. METHODS: In this retrospective cohort study, 9,346 adults who visited a primary care clinic of a large health maintenance organization completed a survey about nine adverse childhood experiences: experiencing childhood emotional, physical, and sexual abuse; witnessing domestic violence; parental separation or divorce; and growing up with drug-abusing, mentally ill, suicidal, or criminal household members. The associations between parental alcohol abuse, the adverse experiences, and alcoholism and depression in adulthood were assessed by logistic regression analyses. RESULTS: The risk of having had all nine of the adverse childhood experiences was significantly greater among the 20 percent of respondents who reported parental alcohol abuse. The number of adverse experiences had a graded relationship to alcoholism and depression in adulthood, independent of parental alcohol abuse. The prevalence of alcoholism was higher among persons who reported parental alcohol abuse, no matter how many adverse experiences they reported. The association between parental alcohol abuse and depression was accounted for by the higher risk of having adverse childhood experiences in alcoholic families. CONCLUSIONS: Children in alcoholic households are more likely to have adverse experiences. The risk of alcoholism and depression in adulthood increases as the number of reported adverse experiences increases regardless of parental alcohol abuse. Depression among adult children of alcoholics appears to be largely, if not solely, due to the greater likelihood of having had adverse childhood experiences in a home with alcohol-abusing parents.     

精神分裂症高危人群的认知功能与焦虑、抑郁及精神病性症状

目的评估精神分裂症高危人群的认知功能与焦虑、抑郁及精神病性症状,为该人群的早期干预提供科学依据.方法收集来源于中国医科大学附属第一医院精神医学科和沈阳市精神卫生中心就诊的门诊和住院的精神分裂症患者健康子女109人作为精神分裂症遗传高危组,通过广告招募的与精神分裂症患者健康子女年龄、性别、受教育年限相匹配的健康人群,共109人作为健康对照组.两组分别完成威斯康星卡片测试(WCST)、认知成套测试(MCCB)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD-17)和简明精神症状量表(BPRS)测试.对两组被试者的一般人口学资料、认知状况及临床特征进行统计分析处理.结果(1)精神分裂症高危组在执行功能WCST卡片测试中的总正确数(Z=-4.54,P<0.01)、正确分类数(Z=-3.78,P<0.01)、总错误数(Z=-4.49,P<0.01)、持续错误数(Z=-3.91,P<0.01)及非持续错误数(Z=-3.38,P<0.01)与健康对照组比较,差异有统计学意义;(2)精神分裂症高危组在MCCB总分(t=11.58,P<0.01)、符号编码(t=11.25,P<0.01)、视觉空间记忆(t=4.59,P=0.04)、持续操作测验(t=6.18,P=0.02)显著低于健康对照组;(3)精神分裂症高危组在HAMA总分(t=2.54,P=0.01)、HAMD-17总分(t=3.03,P<0.01)和抑郁量表中的躯体性焦虑因子(t=2.70,P<0.01)、核心抑郁因子(t=3.04,P<0.01)评分显著高于健康对照组;(4)精神分裂症高危组在BPRS总分(t=3.14,P<0.01)、焦虑和抑郁因子分(t=2.90,P<0.01)亦显著高于健康对照组.结论精神分裂症高危人群不仅存在认知功能损害,而且焦虑、抑郁以及精神病性症状高于健康人群.     

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.     

Assessing depression in youth at clinical high risk for psychosis: A comparison of three measures

Depressive symptoms are prevalent among individuals at clinical high-risk (CHR) for psychosis. Prior studies have used the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), and the “dysphoric mood” item of the Scale of Prodromal Symptoms (SOPS) to assess depressive symptoms in CHR samples. We compared the psychometric properties of these instruments in a CHR cohort, to support the selection of appropriate depressive symptoms measures in future studies and in clinical settings. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through correlations with SOPS items that were expected or not expected to be related to depressive symptoms. Criterion validity was assessed by comparing scores between patients with and without a major depressive disorder diagnosis. We hypothesized based on the schizophrenia literature that the BDI would have superior internal consistency and discriminant validity compared to the HDRS, and that all three measures would show convergent validity and criterion validity. The BDI demonstrated superior internal consistency and construct validity in this at-risk sample. The BDI and HDRS differentiated patients with major depressive disorder, but SOPS dysphoria did not. This has implications for the choice of depression measures in future CHR studies and for the interpretation of past findings.     

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.     

Parents of childhood X-linked adrenoleukodystrophy: high risk for depression and neurosis

The purpose of this study was to assess mental health in parents of patients with the childhood cerebral form of X-linked adrenoleukodystrophy (CCALD) and to investigate factors relating to psychological problems in order to improve clinical management and quality of life. Sixteen fathers and 21 mothers of patients with CCALD completed a battery of psychological examinations including the Beck Depression Inventory second edition (BDI-II), the General Health Questionnaire 60 (GHQ60), and the State-Trait Anxiety Inventory (STAI). Three fathers and 11 mothers showed high scores on the BDI-II, suggesting that they were in a depressive state. Depression in the mothers was serious as compared with previous reports. Six fathers and 11 mothers were considered to be in a state of neurosis, according to the results of the GHQ60. Four fathers and 8 mothers showed high levels of anxiety on the STAI. Health and social status of the mothers correlated with their mental health, and younger mothers with young patients tended to be more depressed. Thus, parents of patients with CCALD have a high risk of depression and neurosis. Understanding the mental state of these parents and improvements in the social support system including mental counseling, home nursing care, supports in workplace and community are necessary to prevent and treat psychological problems. Especially, early intervention for mental health problems should be provided for younger mothers with few years since the child's diagnosis.     

Children of parents with bipolar disorder. A population at high risk for major affective disorders

Children of parents who suffer from bipolar disorder are largely ignored by psychiatric services despite the fact that they constitute a population at very high risk for major depression and bipolar disorder in adulthood and a wide variety of disorders in childhood and adolescence. Major depression and bipolar disorder are chronic, recurrent disorders that seriously impair psychosocial functioning across the life-span. Evidence suggests that in this population bipolar disorder is preceded by externalizing disorders in childhood in many cases, and by depression in some cases. While heredity provides the vulnerability for the development of these characteristics, being raised by parents who model inappropriate coping skills, create a stressful family environment, and provide inadequate support and structure, contribute to consolidating these characteristics.