 |
|
Parental Major Depression and the Risk of Depression and Other Mental Disorders in Offspring
A Prospective-Longitudinal Community Study
Roselind Lieb, PhD;
Barbara Isensee, DiplPsych;
Michael Höfler, DiplStat;
Hildegard Pfister, DiplInf;
Hans-Ulrich Wittchen, PhD
Arch Gen Psychiatry. 2002;59:365-374.
ABSTRACT
| |
Background This article examines associations between DSM-IV depressive disorders, their natural course, other psychopathology,
and parental major depression in a community sample of adolescents and young
adults.
Methods Baseline and 4-year follow-up data were used from the Early Developmental
Stages of Psychopathology Study, a prospective-longitudinal community study
of adolescents and young adults. Results are based on 2427 subjects who completed
the follow-up and for whom diagnostic information for both parents was available. DSM-IV mental disorders in respondents were assessed using
the Munich-Composite International Diagnostic Interview. Information on depression
in parents was collected as family history information from the respondents
and from diagnostic interviews with parents of the younger cohort.
Results Offspring with 1 (odds ratio [OR], 2.7; 95% confidence interval [CI],
2.1-3.5) or 2 affected parents (OR, 3.0; 95% CI, 2.2-4.1) had an increased
risk for depression. They also had a higher risk for substance use (1 parent
affected: OR, 1.4; 95% CI, 1.1-1.7; both parents affected: OR, 1.4; 95% CI,
1.0-1.8) and anxiety disorders (1 parent affected: OR, 1.6; 95% CI, 1.3-1.9;
both parents affected: OR, 2.1; 95% CI, 1.6-2.8). There were no differences
whether mother or father was affected. Parental depression was associated
with an earlier onset and a more malignant course (severity, impairment, recurrence)
of depressive disorders in offspring.
Conclusions Major depression in parents increases the overall risk in offspring
for onset of depressive and other mental disorders and influences patterns
of the natural course of depression in the early stages of manifestation.
INTRODUCTION
AVAST NUMBER of studies have investigated the association between depression
in parents and psychopathology in their offspring. Studies using the "top-down"
approach have consistently shown that offspring of depressed parents have
a substantially increased risk for experiencing not only depressive disorders,
but also other psychopathology, such as anxiety or substance-use disorders.1-17
From another perspective, "bottom-up" studies examining clinically referred
depressed children and adolescents have reported increased rates of depression
and other forms of psychopathology in their adult relatives.18-25
Although the association between parental depression and offspring psychopathology
seems to be sufficiently studied, there are several weaknesses of previous
research. Thus, with 2 exceptions,14-15
all studies have included affected individuals (either parent or child) in
treatment as index probands. Because of the effects of self-selection, treatment,
and help-seeking bias, these results may not be representative of depressive
disorders in general.26 Further, most studies
have failed to consider diagnostic comorbidity within the affected parents,
so it is often not clear whether the reported associations are unique for
parental depression or whether the associations may also be explained by confounding
comorbid disorders in parents.15, 27
Additionally, most studies have focused on diagnostic status in the mother
or in either parent, and only a few have evaluated associations separately
for affected mothers and fathers or different levels of parental loading.2-3,7, 17
A final, understudied issue is the natural course of depressive disorders
in offspring of affected parents in terms of onset, severity, persistence,
and risk of recurrence. A precise picture of the natural course of depressive
disorders in these offspring requires prospective-longitudinal designs. Although
during the past decade there have been methodologically sound longitudinal
studies of offspring of depressed parents that suggest that parental depression
leads to an earlier onset as well as a more complicated course of depression
in the offspring,7-10,13-14
none of them have used a representative community sample to evaluate such
specific course characteristics.
The present study examines, on the basis of a representative community
sample of adolescents and young adults, the association of a history of major
depression in parents with depression and other mental disorders, along with
the course of depression in offspring in terms of age of onset, severity,
and impairment.
SUBJECTS AND METHODS
SAMPLE
Data come from the Early Development Stages of Psychopathology Study
(EDSP), a prospective-longitudinal study designed to collect data on the prevalence,
incidence, familial risk and other risk factors, comorbidity, and course of
mental disorders in a representative sample of 3021 respondents aged 14 to
24 years at baseline. These respondents represent the offspring in this report.
The EDSP consists of a baseline survey, 2 follow-up surveys, and a family
supplement. Detailed descriptions of the study are reported elsewhere.28-29 The baseline sample was drawn in
1994 from the government registries in Munich, Germany, of registrants expected
to be 14 to 24 years of age at the time of the baseline interview in 1995.
Details about the sampling and representativeness of the whole EDSP sample,
along with its sociodemographic characteristics, have been previously presented.28-30 A total of 3021 interviews
were completed at baseline (T0; response rate, 71%). The first follow-up study
(T1) was conducted only for respondents aged 14 to 17 years at baseline, whereas
the second follow-up study was conducted for all respondents. In the first
follow-up, which took place at an average of 20 months after baseline, a total
of 1228 interviews were completed (response rate, 88%). From the 3021 respondents
of the baseline study, a total of 2548 interviews were completed at the second
follow-up (T2), which occured at an average of 42 months after baseline (response
rate, 84%).
In the EDSP family supplement, direct diagnostic interviews were conducted
with the parents of the younger cohort (the 14- to 17-year-olds at baseline).29 As we were interested not only in familial psychopathology,
but also in early developmental information about the respondents, primarily
the mothers were interviewed. Fathers were interviewed only if the mother
was not available (deceased or not locatable). The parents of 1053 adolescents
were interviewed directly (in 1026 cases the mother, in 27 cases the father;
response rate, 86%).
The results reported in this article are based on the 2427 respondents
who completed the whole study period and for whom diagnostic information about
psychopathology in both parents was available. Throughout the article, data
are weighted by age, sex, geographic location, noncontact, and nonresponse
to match the distribution of the sampling frame.29
DIAGNOSTIC ASSESSMENT OF OFFSPRING
Diagnoses of the offspring are based on the DSM-IV31 and were assessed with the computer-assisted
version of the Munich-Composite International Diagnostic Interview (M-CIDI32), an updated version of the World Health Organization's
Composite International Diagnostic Interview version 1.2.33
The reliability and validity of the M-CIDI have been reported.34-36
Diagnostic findings were obtained by using the M-CIDI/DSM-IV diagnostic algorithms. In all assessments, interviews were administered
by highly trained clinical interviewers—mostly graduate students in
psychology. Most interviews were carried out in the homes of the respondents.
The diagnoses considered in this article include depressive disorders
(major depression, dysthymia), bipolar disorders (bipolar I and bipolar II
disorders), anxiety disorders (panic disorder with and without agoraphobia,
agoraphobia without panic disorder, specific phobia, phobia not otherwise
specified, social phobia, generalized anxiety disorder, obsessive-compulsive
disorder, and posttraumatic stress disorder), and substance use disorders
(alcohol abuse and dependence, nicotine dependence, and illicit drug abuse
and dependence). Descriptors of the severity of depression (eg, number of
depressive episodes, impairment, treatment seeking) refer to the self-identified
worst episode of depression. Overall impairment due to depression was assessed
by asking the respondents how much their depression impaired daily life and
activities during the worst period. Social role–specific impairment
was assessed by questions in which respondents were asked how much during
the 4 weeks preceding the interview depressive symptoms made them feel impaired
in (1) daily activities such as work, house work, or studies; (2) leisure-time
activities; and (3) social contact with family, friends, and colleagues.
At baseline, the lifetime version of the M-CIDI was used. At each of
the follow-up assessments, we applied the M-CIDI interval version, which refers
to the period of assessment from the last interview until the present. For
those respondents aged 14 to 17 years at baseline, the complete follow-up
status from baseline to second follow-up is assessed from the aggregation
of information obtained from the first and second follow-up interviews. For
respondents older than 17 years at baseline, the complete follow-up status
is assessed from the second follow-up questions, which cover the time between
baseline and second follow-up.
PARENTAL HISTORY
In a separate M-CIDI family history module administered at baseline
and second follow-up, respondents provided family history information on all
first-degree relatives. Family history items were designed using a modified
version of the Family History Research Diagnostic Criteria37
as a model. To obtain family history information about the same DSM-IV diagnoses that are in the M-CIDI, M-CIDI stem questions were
used at baseline. Questions to determine whether the relative sought professional
help because of his or her respective symptoms were also asked. In the second
follow-up, we used an extended version of the family history module, which
contained fully structured sections covering DSM-IV
criteria.
Parents of the younger cohort were independently assessed with the M-CIDI
in the EDSP family supplement, providing direct diagnostic information about
the interviewed parent. Interviewers were blinded to the diagnostic findings
of the respective offspring. The parent M-CIDI contained a module that provided
family history data for the noninterviewed parent and other family members
of the respondent.38-39
Family history status of major depression was determined by using all
available diagnostic information about the occurrence of any major depression
episode in parents. Diagnostic estimates for the parents of the younger cohort
took into account the family history data obtained from the respondent as
informant, as well as the M-CIDI information and family history data obtained
from the parent interview.39 For the older
cohort, for which no direct parent interviews were available, we used only
family history information obtained from the respondent. The accuracy of family
history information was examined by comparing the diagnostic information obtained
from the respondents about their mothers, with the information obtained from
the mothers themselves. This was also achieved by comparing the family history
information obtained from the respondents about their fathers, with the family
history information obtained from the mothers about the fathers. Overall,
only moderate sensitivity (48% for the detection in mothers, 63% for the detection
in fathers), but acceptable high specificity (68% for mothers, 85% for fathers),
was found for major depression. For this article, any indication of a major
depressive episode was accepted for a positive diagnosis in parents. Therefore,
the diagnostic certainty should be interpreted on the "probable" level.39
STATISTICAL ANALYSES
As our goal was to examine the degree to which parental major depression
is associated with diagnostic outcomes in children, parental major depression
was the independent variable. Main diagnostic outcomes were the offspring's
cumulative lifetime incidences of DSM-IV depressive
and other mental disorders at second follow-up, which were calculated by adding
baseline and follow-up incident cases.
For the analyses of associations between major depression in parents
and psychopathology in offspring, logistic regressions for binary responses
(odds ratio [OR]) were used. For the analysis of impairment variables, cumulative
logistic regressions were used. Hereby, it is assumed that the covariates
are related to a shift on a latent continuum that underlies the observed categories,
and this overall association is described with cumulative ORs (CUMORs). This
provides more statistical precision in estimates as compared with dichotomization.40
For quantitative outcomes of severity of depression that were count
variables (values of 0, 1, 2, ...; eg, the number of depressive episodes),
negative binomial regressions were used. Hereby, the skewness of these variables
is taken into account, as well as overdispersion (when a variance is higher
than expected under the Poisson model for the dependent variable conditional
on the covariate values41). Associations are
described by incidence rate ratios (ie, the factor by which the mean differs
from the mean in the comparison group).
Age-specific cumulative lifetime incidences were estimated with the
Kaplan-Meier-method42 using age of onset information
from the offspring. Statistical inferences are based on the stratified Cox
model for discrete time (ie, before testing for differences, different curves
in strata defined by birth year cohorts and sex of the offspring are calculated
nonparametrically42). The interaction term
parental major depressionxage was added to the model when the proportional
hazards assumption was violated. The latter was tested with Schoenfeld residuals.43 This was done to see whether offspring with affected
parents have an earlier onset of the disorder under consideration. Such a
model provides hazard ratios (HRs) for the main effect of parental major depression
and for the interaction effect with age. An HR less than 1 for the interaction
term indicates that offspring with affected parents have an earlier onset
than offspring without affected parents. The age-specific HR for the effect
of parental major depression is given by the following:
When Cox analyses were conducted with multiple anxiety or substance
use disorders, the age of onset of the chronologically earliest disorder was
used.
Analyses were performed using the Stata software package44
and applying the Huber-White sandwich matrix for weighted data.45
Sex and age of offspring were controlled for by including them as independent
variables in the respective model. P <.05 was
considered statistically significant. All associations were tested for interaction
with sex of offspring, and in cases of significant effects, associations were
then separately determined for males and females. To protect for misleading
results obtained by aggregating 2 cohorts with different ascertainment strategies,
all associations were tested for an interaction effect with age cohort. In
case of significance, analyses were run separately within each cohort.
RESULTS
PREVALENCES
Study criteria for major depression were fulfilled by 42.1% of mothers
and 23.4% of fathers (Table 1).
In 33.7% and 16.0% of the sample, respectively, one (mother only, 26.2%; father
only, 7.5%) or both parents were affected. Of the offspring, 19.5% reported
at least 1 episode of major depression by the second follow-up, and 3.8% fulfilled
criteria for lifetime dysthymia. Substance use disorders were reported by
43.1% of the offspring when nicotine dependence was included, and by 31.3%
of the offspring when nicotine dependence was excluded. Bipolar disorders
were reported by 3.1%; and any anxiety disorder, by 35.0% of the offspring.
Depressive and anxiety disorders were more common in female offspring than
in male offspring, while substance use disorders were more common in male
offspring than in female offspring. No gender differences were found for bipolar
disorders.
|
|
|
|
Table 1. Major Depression in Parents and Cumulative Lifetime Incidence
Rates of DSM-IV Depressive and Other Disorders in
Offspring*
|
|
|
ASSOCIATIONS BETWEEN PARENTAL DEPRESSION AND PSYCHOPATHOLOGY IN OFFSPRING
Compared with the offspring of nondepressed parents, offspring of either
1 or 2 depressed parents reported higher rates of depression and almost all
other disorders under consideration (Table
2). With few exceptions, risks were similar in offspring with 1
vs 2 affected parents. The exceptions were bipolar II, obsessive-compulsive
disorder, posttraumatic stress disorder, and the aggregated category of anxiety
disorders, for which risks were higher in offspring with 2 affected parents.
In general, adjusting for parental comorbidity yielded similar results. Only
the associations between parental depression and alcohol dependence, agoraphobia,
phobia not otherwise specified, and social phobia in offspring failed to reach
significance, suggesting that the increased rates of these disorders in the
offspring may be due to comorbid disorders in the parents. In an effort to
exclude the hypothesis that the lack of differences between 1 and 2 depressed
parents could be explained by coparental psychopathology in offspring with
1 affected parent, we additionally reran the analyses controlling for coparental
psychopathology. These analyses yielded similar findings.
|
|
|
|
Table 2. Lifetime Association of Parental Major Depression With DSM-IV Depressive and Other Mental Disorders in Their Offspring*
|
|
|
All parent-offspring associations were tested for differences between
male and female offspring. In general, associations were comparable in size
for sons and daughters. Interaction effects were found only as follows: among
offspring of 1 affected parent, only males had a higher risk for panic disorder,
while among offspring of 2 affected parents, only females had a higher risk
for specific phobia as well as for any anxiety disorder. The examination of
interaction with cohort revealed that among offspring of 2 affected parents,
risk for agoraphobia was increased only in the older cohort.
SEX OF AFFECTED PARENT
To examine whether the pattern of associations differed by sex of the
affected parent, analyses were conducted after dividing offspring into those
with an affected mother only and those with an affected father only. Compared
with the offspring of nonaffected parents, offspring of both groups had higher
rates of depression and other mental disorders (Table 3). Associations were not different between maternal and paternal
depression.
|
|
|
|
Table 3. Cumulative Lifetime Rates of DSM-IV
Mental Disorders by Gender of Affected Parent*
|
|
|
With the exception of male offspring of affected mothers having a higher
risk for panic disorder, no notable differences in risks were found between
male and female offspring. The examination of interaction with the cohort
revealed only one effect: among the offspring of affected fathers, risk for
any substance use disorder (including or excluding nicotine dependence) was
increased only in the younger cohort.
MAJOR DEPRESSION IN PARENTS AND AGE OF ONSET
Figure 1 shows the offsprings'
age-specific probability of developing any type of depression by number of
affected parents. First onset of any depressive disorder was earlier in offspring
with 2 affected parents when compared with offspring without affected parents
(for interaction with age, HR = 0.9, 95% confidence interval [CI] = 0.8-0.9;
for main effect from this model, HR = 8.5, 95% CI = 2.9-24.6), whereas there
was no such finding when only 1 parent was affected (for interaction with
age, HR = 1.0, 95% CI = 0.9-1.0; for main effect from this model, HR = 2.5,
95% CI = 0.6-9.5). Age of onset characteristics were also examined separately
for major depression and dysthymia. Both disorders started earlier in offspring
with 2 affected parents than in offspring without affected parents (major
depression: for interaction with age, HR = 0.9, 95% CI = 0.8-0.9; for main
effect from this model, HR = 9.2, 95% CI = 2.7-31.3) (dysthymia: for interaction
with age, HR = 0.9, 95% CI = 0.7-0.9; for main effect from this model, HR
= 29.9, 95% CI = 5.0-176.1).
|
|
|
|
Age of onset of any depression in offspring, by parental history
of major depression. Nw indicates number of subjects.
|
|
|
Because of restricted sample sizes in some specific anxiety disorders,
age of onset characteristics were determined for the main diagnostic group
of "any anxiety disorder." For anxiety disorders, no interactions between
age of onset in offspring and parental depression were found. Concerning substance
use disorders, age of onset characteristics were separately evaluated for
nicotine dependence, alcohol dependence, and abuse or dependence of any illicit
drugs. Offspring with 2 affected parents develop drug abuse or dependence
earlier (for interaction with age, HR = 0.8, 95% CI = 0.6-0.9; for main effect
from this model, HR = 34.8, 95% CI = 1.9-615.9) as compared with offspring
without affected parents. By contrast, the age of onset for nicotine dependence
and for alcohol use disorders did not vary by parental diagnostic status.
All interaction effects proved similar when adjusting for parental comorbidity.
CLINICAL CHARACTERISTICS BY PARENTAL MAJOR DEPRESSION
As indicated by several clinical characteristics, severity of depression
was greater in offspring of affected parents than in offspring of nonaffected
parents. Overall, offspring of depressed parents reported higher persistence,
more depressive episodes, increased rates of treatment seeking (Table 4), and also higher impairments in social contacts and leisure
activities (Table 5).
|
|
|
|
Table 4. Severity and Treatment Seeking for Parental Major Depression*
|
|
|
|
|
|
|
Table 5. Impairment by Parental Major Depression*
|
|
|
COMMENT
Consistent with most previous reports,4, 8-10,13-15,19-20,23-25
we found that parental major depression increases offspring risk for depression.
Our results, however, are an extension of previous findings insofar as (1)
parent-offspring associations were explored using DSM-IV criteria in a representative sample, (2) subjects were examined prospectively
across the period of risk of initial onset of depressive disorders, and (3)
the use of a large sample size promises power benefits for the statistical
analyses.
Depression in parents was associated not only with offspring depression
but also with other psychopathology (ie, anxiety or specific substance use
disorders). These associations remained stable even after adjustment for parental
comorbidity. The literature contains mixed findings regarding the specificity
of the familial transmission of major depression.10, 15, 18-19,23-24
We found that within-disorder associations (eg, parental depression with depression
in offspring) were in most cases, considerably higher than cross-disorder
associations (eg, parental depression with anxiety disorders in offspring),
suggesting a certain specificity of the parent-offspring associations of depression.
Nevertheless, our cross-disorder findings also deserve attention. The higher
risk for nicotine dependence in offspring is especially interesting as it
has never before been reported. Previous studies46-47
found that early anxiety and depression predict later nicotine dependence.
Thus, familial transmitted anxiety and depression in children might increase
the risk for subsequent nicotine dependence, or the familial association might
indicate shared etiologies48-49
for these 2 disorders.
Unlike most studies, we additionally examined associations by sex of
the affected parent. Although it is critical that the diagnostic procedures
were not entirely comparable between mothers and fathers, our findings suggest
that maternal and paternal depression affect male and female offspring similarly.
These results are in line with those of other family genetic studies,3-5,7, 15, 17, 19-20,50
which found no compelling evidence for substantial sex-specific effects in
the familial transmission of depression.
We also showed that the offspring of affected parents experience a more
malignant course of depression, which that is manifested by a higher number
of depressive episodes, higher persistence, and higher treatment seeking.
These findings are consistent with observations in clinical studies10, 14 in which parental depression is associated
with higher illness severity in offspring. Further, the literature provides
some evidence that early-onset depression may constitute a "familial subtype"
of depression.10 Overall, our finding that
offspring of 2 affected parents have an earlier onset of depression supports
this hypothesis; however, our results also indicate a potentially differential
influence of parental concordance on this outcome. To our knowledge, this
effect has not been reported before, but it indicates that the diagnostic
status of both parents should be considered in future studies.
In terms of parental loading, having 1 or 2 affected parents seems to
equally influence the offspring's risk for depression. Although one might
expect a monotonic relationship between the number of affected parents and
the same disorder in the offspring, our findings, together with the findings
of other clinical studies7, 17
do not support such a hypothesis. Whatever the explanation of this observation
might be (eg, mobilization of protective factors when both parents are affected),
this lack of systematic effect of different parental loading suggests that
the familial transmission of depression does not follow simple patterns. Beardslee
et al51 and Rutter et al,52
who reviewed the research on genetic and environmental factors in this field,
concluded that parental depression probably exerts its influence on offspring
through several genetic and environmental factors that most likely interact
in very complex patterns. An important topic for future research would be
to unravel these patterns of environmental and genetic influences that increase
vulnerability53 for depression.
Our findings should be interpreted with caution because the inclusion
of family history information might have produced biased estimates of parental
psychopathology. One concern in this respect is the rather low sensitivity
of family history information.54-57
To increase sensitivity, all available diagnostic information about probable
major depression in parents was used. This might explain the relatively high
rate of depressive disorders in parents. Another concern is whether family
history information is influenced by the respondents' diagnostic status.58-59 We examined whether respondents with
mental disorders demonstrated higher sensitivity for parental psychopathology
when compared with unaffected respondents, but we found no evidence for biased
estimates. The use of family history information could also have caused an
underestimation of comorbidity among depressed parents and, therefore, an
attenuation of specificity. Further, different assessment stategies were used
for ascertainment of parental psychopathology in the 2 age cohorts. To protect
for misleading results obtained by aggregating both cohorts, all associations
were tested for interaction with age cohort. As we found only 2 cohort effects,
the different ascertainment strategies probably did not systematically bias
our findings. Although the young age of our sample makes it rather unlikely
that onset of depression in offspring preceded the onset of depression in
parents, we cannot absolutely guarantee this temporal ordering in all cases.
This issue could not be addressed in the analyses, as information about age
of onset in parents was not assessed in the family history interviews. Finally,
not all respondents have fully passed through the entire risk period for onset
of mental disorders, but the inclusion of false-negative cases probably resulted
in diminished, rather than overestimated, associations.
This study has once more demonstrated that offspring of depressed parents
constitute an important high-risk group. Our findings argue for specific prevention
and intervention efforts in those offspring. Specifically, the early detection
of mental health problems in offspring of depressed parents seems to be crucial,
as this would allow the treatment of early manifestations of mental problems
before they cause clinical impairment.
AUTHOR INFORMATION
Submitted for publication January 18, 2001; final revision received
July 27, 2001; accepted August 13, 2001.
This work is part of the Early Developmental Stages of Psychopathology
Study and is funded by the German Ministry of Research and Technology, projects
01 EB 9405/6 and 01 EB 9901/6.
The authors wish to thank Robin Carter, BA, Robert Friis, PhD, and the
anonymous reviewers for their helpful comments and suggestions.
| Early Developmental Stages of Psychopathology
Study Group
Principal Investigators
Hans-Ulrich Wittchen, PhD; Roselind Lieb, PhD
Current and Former Staff Members
Kirsten von Sydow, PhD; Gabriele Lachner, PhD; Axel Perkonigg, PhD;
Peter Schuster, PhD; Franz Gander, PhD; Michael Höfler, DiplStat; and
Holger Sonntag, DiplPsych, as well as Esther Beloch, MagPhil; Martina Fuetsch,
PhD; Elzbieta Garczynski, DiplPsych; Alexandra Holly, DiplPsych; Barbara Isensee,
DiplPsych; Marianne Mastaler, PhD; Chris Nelson, PhD; Hildegard Pfister, DiplInf;
Victoria Reed, DiplPsych; Dilek Türk, DiplPsych; Antonia Vossen, DiplPsych;
Ursula Wunderlich, PhD; and Petra Zimmermann, DiplPsych
Scientific Advisors
Jules Angst, MD (Zurich, Switzerland); Jürgen Margraf, PhD (Basel,
Switzerland); Günther Esser, PhD (Mannheim, Germany); Kathleen Merikangas,
PhD (New Haven, Conn); and Ron Kessler, PhD (Boston, Mass)
|
|
Corresponding author and reprints: Roselind Lieb, PhD, Clinical Psychology
and Epidemiology Unit, Max Planck Institute of Psychiatry, Kraepelinstr. 2,
80804 Munich, Germany (e-mail: lieb{at}mpipsykl.mpg.de).
From the Clinical Psychology, and Epidemiology Unit, Max Planck Institute
of Psychiatry, Munich (Drs Lieb and Wittchen, Mss Isensee and Pfister, and
Mr Höfler), and the Department of Clinical Psychology and Psychotherapy,
Technical University of Dresden, Dresden (Dr Wittchen), Germany.
REFERENCES
| |
1. Keller MB, Beardslee WR, Dorer DJ, Lavori PW, Samuelson H, Klerman GR. Impact of severity and chronicity of parental affective illness on
adaptive functioning and psychopathology in children. Arch Gen Psychiatry. 1986;43:930-937.
ISI
| PUBMED
2. Klein DN, Clark C, Dansky L, Margolis ET. Dysthymia in the offspring of parents with primary unipolar affective
disorder. J Abnorm Psychol. 1988;97:265-274.
FULL TEXT
|
ISI
| PUBMED
3. Merikangas KR, Prusoff BA, Weissman MM. Parental concordance for affective disorders: psychopathology in offspring. J Affect Disord. 1988;15:279-290.
FULL TEXT
|
ISI
| PUBMED
4. Orvaschel H, Walsh-Allis G, Ye W. Psychopathology in children of parents with recurrent depression. J Abnorm Child Psychol. 1988;16:17-28.
FULL TEXT
|
ISI
| PUBMED
5. Keller MB, Beardslee W, Lavori PW, Wunder J, Samuelson H. Course of major depression in non-referred adolescents: a retrospective
study. J Affect Disord. 1988;15:235-243.
FULL TEXT
|
ISI
| PUBMED
6. Fendrich M, Warner V, Weissman MM. Family risk factors, parental depression, and psychopathology in offspring. Dev Psychol. 1990;26:40-50.
7. Radke-Yarrow M, Nottelmann E, Martinez P, Fox MB, Belmont B. Young children of affectively ill parents: a longitudinal study of
psychosocial development. J Am Acad Child Adolesc Psychiatry. 1992;31:68-77.
ISI
| PUBMED
8. Weissman MM, Fendrich M, Warner V, Wickramaratne PJ. Incidence of psychiatric disorders in offspring at high and low risk
for depression. J Am Acad Child Adolesc Psychiatry. 1992;31:640-648.
ISI
| PUBMED
9. Weissman MM, Gammon D, John K, Merikangas KR. Children of depressed parents. Arch Gen Psychiatry. 1987;44:847-853.
ISI
| PUBMED
10. Weissman MM, Warner V, Wickramaratne P, Moreau D, Olfson M. Offspring of depressed parents: 10 years later. Arch Gen Psychiatry. 1997;54:932-940.
ISI
| PUBMED
11. Warner V, Mufson I, Weissman MM. Offspring at high and low risk for depression and anxiety: mechanisms
of psychiatric disorder. J Am Acad Child Adolesc Psychiatry. 1995;34:786-797.
FULL TEXT
|
ISI
| PUBMED
12. Warner V, Weissman MM, Mufson L, Wickramaratne P. Grandparents, parents, and grandchildren at high risk for depression:
a three-generation study. J Am Acad Child Adolesc Psychiatry. 1999;38:289-296.
FULL TEXT
|
ISI
| PUBMED
13. Hammen C, Burge D, Burney E, Cheri A. Longitudinal study of diagnoses in children of women with unipolar
and bipolar affective disorder. Arch Gen Psychiatry. 1990;47:1112-1117.
ISI
| PUBMED
14. Beardslee WR, Keller MB, Seifer R, Lavori PW, Staley J, Podorefsky D, Shera D. Prediction of adolescent affective disorder: effects of prior parental
affective disorders and child psychopathology. J Am Acad Child Adolesc Psychiatry. 1996;35:279-288.
FULL TEXT
|
ISI
| PUBMED
15. Kendler KS, Davis CG, Kessler RC. The familial aggregation of common psychiatric and substance use disorders
in the National Comorbidity Survey: a family history study. Br J Psychiatry. 1997;170:541-548.
FREE FULL TEXT
16. Wickramaratne PJ, Weissman MM. Onset of psychopathology in offspring by developmental phase and parental
depression. J Am Acad Child Adolesc Psychiatry. 1998;37:933-942.
FULL TEXT
|
ISI
| PUBMED
17. Dierker LC, Merikangas KR, Szatmari P. Influence of parental concordance for psychiatric disorders on psychopathology
in offspring. J Am Acad Child Adolesc Psychiatry. 1999;38:280-288.
FULL TEXT
|
ISI
| PUBMED
18. Mitchell J, McCauley E, Burke P, Calderon R, Schloredt K. Psychopathology in parents of depressed children and adolescents. J Am Acad Child Adolesc Psychiatry. 1989;28:352-357.
ISI
| PUBMED
19. Puig-Antich J, Goetz D, Davies M, Kaplan T, Davies S, Ostrow L, Asnis L, Twomey J, Iyengar S, Ryan ND. A controlled family history study of prepubertal major depressive disorder. Arch Gen Psychiatry. 1989;46:406-418.
ISI
| PUBMED
20. Williamson DE, Ryan ND, Birmaher B, Dahl RE, Kaufman J, Rao U, Puig-Antich J. A case-control family history study of depression in adolescents. J Am Acad Child Adolesc Psychiatry. 1995;34:1596-1607.
FULL TEXT
|
ISI
| PUBMED
21. Todd R, Geller B, Neuman R, Fox LW, Hickok J. Increased prevalence of alcoholism in relatives of depressed and bipolar
children. J Am Acad Child Adolesc Psychiatry. 1996;35:716-724.
FULL TEXT
|
ISI
| PUBMED
22. Todd R, Neuman R, Geller B, Fox LW, Hickok J. Genetic studies of affective disorders: should we be starting with
childhood onset probands? J Am Acad Child Adolesc Psychiatry. 1993;32:1164-1171.
ISI
| PUBMED
23. Harrington R, Rutter M, Weissman MM, Fudge H, Groothues C, Bredenkamp D, Pickles A, Rende R, Wickramaratne P. Psychiatric disorders in the relatives of depressed probands, I: comparison
of prepubertal, adolescent and early adult onset cases. J Affect Disord. 1997;42:9-22.
FULL TEXT
|
ISI
| PUBMED
24. Kovacs M, Devlin B, Pollock M, Richards C, Mukerji P. A controlled family history study of childhood-onset depressive disorder. Arch Gen Psychiatry. 1997;54:613-623.
ISI
| PUBMED
25. Neuman R, Geller B, Rice JP, Todd R. Increased prevalence and earlier onset of mood disorders among relatives
of prepubertal versus adult probands. J Am Acad Child Adolesc Psychiatry. 1997;36:466-473.
FULL TEXT
|
