Research

JAMA Psychiatry | Original Investigation

Family History of Psychiatric Disorders as a Risk Factor

for Maternal Postpartum Depression
A Systematic Review and Meta-analysis
Mette-Marie Zacher Kjeldsen, MSc; Alessio Bricca, PhD; Xiaoqin Liu, PhD; Vibe G. Frokjaer, MD, PhD;
Kathrine Bang Madsen, PhD; Trine Munk-Olsen, PhD

Supplemental content
IMPORTANCE Current evidence on the association between family history of psychiatric
disorders and postpartum depression is inconsistent; family studies have identified familial
risk of postpartum depression, whereas systematic reviews and umbrella reviews, compiling
all risk factors for postpartum depression, often have not.

OBJECTIVE To investigate the association between family history of psychiatric disorders and
risk of developing postpartum depression within 12 months post partum.

DATA SOURCES Literature searches were conducted in PubMed, Embase, and PsycINFO in
September 2021 and updated in March 2022, accompanied by citation and reference search.

STUDY SELECTION Studies eligible for inclusion comprised peer-reviewed cohort and
case-control studies reporting an odds ratio (OR) or sufficient data to calculate one for the
association between family history of any psychiatric disorder and postpartum depression.
Study selection was made by 2 independent reviewers: title and abstract screening followed
by full-text screening.

DATA EXTRACTION AND SYNTHESIS Reporting was performed using the MOOSE checklist.
Two reviewers independently extracted predefined information and assessed included
studies for risk of bias using the Newcastle-Ottawa Scale. Data were pooled in a meta-analysis
using a random-effects model. Heterogeneity was investigated with meta-regression,
subgroup, and sensitivity analyses. Publication bias was investigated using a funnel plot, and
GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used
to evaluate the overall certainty of the findings.

MAIN OUTCOMES AND MEASURES The primary outcome was the pooled association between
family history of psychiatric disorders and postpartum depression.

RESULTS A total of 26 studies were included, containing information on 100 877 women.
Meta-analysis showed an increased OR of developing postpartum depression when mothers
had a family history of psychiatric disorders (OR, 2.08; 95% CI, 1.67-2.59; I2 = 57.14%)
corresponding to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum
depression prevalence in the general population. Subgroup, sensitivity, and meta-regression
analyses were in line with the primary analysis. The overall certainty of evidence was deemed
as moderate according to GRADE.

CONCLUSIONS AND RELEVANCE In this study, there was moderate certainty of evidence for
an almost 2-fold higher risk of developing postpartum depression among mothers who have
a family history of any psychiatric disorder compared with mothers without.

Author Affiliations: Author

affiliations are listed at the end of this
article.
Corresponding Author: Mette-Marie
Zacher Kjeldsen, MSc, National
Centre for Register-based Research,
Aarhus University, Fuglesangs Allé 26,
JAMA Psychiatry. 2022;79(10):1004-1013. doi:10.1001/jamapsychiatry.2022.2400 8210 Aarhus V, Denmark
Published online August 17, 2022. (mmzk@econ.au.dk).

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 Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression
T
he postpartum period is critical for mothers, children,
and families, and approximately 10% to 15% of new
mothers experience postpartum depression (PPD),1,2 one
of the most common complications related to childbirth.3 PPD
ranges from mild to severe episodes and includes similar symp-
toms as major depression outside the postpartum period.3 PPD
is preventable and treatable, and therefore, early identifica-
tion of women at high risk is important to prevent or mitigate
the detrimental consequences observed in relation to PPD.4-6
Several risk factors for PPD have been identified and
summarized in systematic reviews; however, having a rela-
tive with a psychiatric disorder is often not listed as a risk
factor in reviews summarizing all identified risk factors.7-18
Recently, 3 comprehensive umbrella reviews, compiling evi-
dence from several systematic reviews on risk factors for PPD,
also did not identify family history of psychiatric disorders
as a risk factor.19-21 The few systematic reviews that have iden-
tified family history of psychiatric disorders as a risk factor
have predominantly been based on a few primary studies, are
often cross-sectional or with small effect sizes, and have in-
consistent findings.22-27 In contrast, familiality of PPD has been
found in observational family studies,28-30 where greater heri-
tability of PPD than major depressive disorders has been
reported.31 This is directly in line with the research on famil-
ial risk of mental disorders outside the postpartum period con-
sistently showing high heritability of psychiatric disorders.32-35
It is therefore puzzling why family history of psychiatric
disorders is not identified as a risk factor in several reviews
focused on all PPD risk factors, when evidence from research
in psychiatry outside the post partum strongly suggests so.
The primary objective of this systematic review and meta-
analysis was to summarize the current literature on the asso-
ciation between family history of psychiatric disorders and PPD
with an onset of 0 to 12 months post partum. The second ob-
jective was to investigate whether the association was modi-
fied by different assessment points and definitions of family
history of psychiatric disorders and PPD.
Methods
This review and meta-analysis was conducted following
the Cochrane Handbook recommendations and reported ac-
cording to the Meta-analysis of Observational Studies in Epi-
demiology (MOOSE) reporting guideline (eMethods 1 in the
Supplement).36,37 The protocol was developed according to
the Preferred Reporting Items for Systematic Reviews and
Meta-analyses Protocols (PRISMA-P) reporting guideline,38
registered in PROSPERO on September 10, 2021, 39 and
published in a peer-reviewed journal.40 See eMethods 2 in the
Supplement for specifications to the protocol.
Eligibility Criteria, Data Sources, and Search Strategy
Cohort and case-control studies investigating family history
of psychiatric disorders as a risk factor for PPD within 12 months
post partum were eligible. Family history of psychiatric dis-
orders was defined as any psychiatric disorder among close and
extended family members obtained through registers, vali-
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Original Investigation Research
Key Points
Question Is the risk of developing postpartum depression higher
for mothers with a family history of psychiatric disorders than
mothers without?
Findings In this systematic review and meta-analysis comprising
26 studies from 5 continents totaling 100 877 women, the risk
of developing postpartum depression was almost twice as high
among mothers who had a family history of psychiatric disorders
compared with mothers without a family history.
Meaning Family history of psychiatric disorders is a strong risk
factor for postpartum depression, which ideally can be identified
through self-report already during pregnancy and enable timely
and targeted preventive initiatives.
dated instruments, or self-reported data. PPD was defined
through registers (prescribed medications for depression treat-
ment; International Statistical Classification of Diseases and
Related Health Problems, Tenth Revision [ICD-10] codes F32,
F33, and F34.1; or equivalent DSM-IV and DSM-5 minor and
major depression), clinical interviews, or validated instru-
ments. To ensure temporality, in cohort studies, information
on family history of psychiatric disorders had to be collected
prior to PPD. For case-control studies, information on family
history of psychiatric disorders should not be self-reported if
collected at the same time as PPD. Furthermore, eligible stud-
ies had to present either an odds ratio (OR) for the association
or sufficient data to estimate an OR, and reporting had to
be distinct for the postpartum period. Finally, only peer-
reviewed English, Norwegian, Swedish, Danish, and Italian
articles were included.
Searches were performed without language or year of
publication restriction in PubMed, Embase, and PsycINFO on
September 12, 2021, accompanied by reference screening and
citation tracking in Web of Science. The search was updated
on March 31, 2022, before finalizing the review. See the pro-
tocol for search strings and construction of them.40
Selection Process and Data Extraction
Records from the database searches were imported to End-
Note, where duplicates were removed. Afterward, records were
imported to an online tool, Covidence, used in the first part of
the screening process.41 The screening process was under-
taken by 2 independent reviewers (M.-M.Z.K. and K.B.M.) and
performed in 2 steps; title and abstract screening followed by
full-text screening. When disagreement occurred during the
title and abstract screening, those studies were referred to
full-text screening. When disagreement occurred in the full-
text screening, 2 other reviewers (X.L. and T.M.-O.) were
consulted. Explanations for the exclusion of each article dur-
ing full-text screening were filled into the PRISMA flowchart.
To ensure similar selection, a training exercise was completed
before initiating the screening process; the 2 reviewers each
evaluated the first 50 articles and discussed disagreements.
In case of articles with missing ORs or insufficient data
to estimate an OR, the authors were contacted up to 3 times
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 Research Original Investigation Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression
to obtain the missing information before exclusion. See the pro-
tocol for elaboration.40 If the study population was already in-
cluded in the review, the authors of the identified article were
not contacted to avoid double counting in the meta-analysis.
Articles fulfilling all criteria for inclusion were included irre-
spective of whether the study sample was already used in an-
other included article, but only the study with the largest popu-
lation size was included in the meta-analysis. Data extraction
was conducted independently by 2 reviewers (M.-M.Z.K. and
K.B.M.) and filled into a predefined Excel form (Microsoft). See
the protocol for more information.40
In articles presenting more than 1 risk estimate for differ-
ent types of family history of psychiatric disorders, decision
on which one to extract was undertaken in 2 steps: if present-
ing a broad definition, eg, family history of mental disorders,
this was extracted. If no broad definition was presented, the
ICD-10 inbuilt hierarchy guided the decision with extraction
of the most severe type of psychiatric disorder.42
A training session was held before data extraction; both
reviewers extracted data from the first 5 articles and com-
pared and discussed. After the exercise, both reviewers inde-
pendently extracted data from the rest of the articles before
comparing and discussing disagreements.
Risk of Bias Assessment
The Newcastle-Ottawa scale was used to assess risk of bias in
all included studies. Both reviewers independently assessed
each study and discussed disparities. The scale has been de-
veloped for assessing case-control and cohort studies and con-
sists of 8 items awarding studies of the highest quality with
a maximum of 9 stars, with higher scores representing lower
risk of bias.43 For elaboration and individual risk of bias scores,
see eMethods 3 in the Supplement.
Data Synthesis and Statistical Analysis
Meta-analyses were performed using a random-effects model
with restricted maximum likelihood given the expected hetero-
geneity of the samples and PPD definitions, using the Meta
command in Stata version 17.0 (StataCorp). When a study re-
ported both unadjusted and adjusted ORs, both were ex-
tracted, but the adjusted estimate was included in the pri-
mary analysis, and both estimates were used in sensitivity
analyses comparing adjusted ORs against unadjusted ORs. If
reporting of estimates at different time points post partum were
reported, all estimates were extracted and used in the second-
ary analysis stratified on PPD assessment time. Only the esti-
mate closest to birth was used in the primary analysis. Statis-
tical heterogeneity between studies was estimated with Q test
and presented through I2.
The primary analysis focused on the pooled association
between family history of psychiatric disorders and PPD. Sec-
ondary analyses were performed to investigate the associa-
tion stratified on assessment time of PPD and definitions of
family history of psychiatric disorders and PPD.
Subgroup analyses were conducted on study design, ge-
ography, sample type, and cumulative and point prevalence
estimates. Sensitivity analysis was conducted on unadjusted
and adjusted estimates and excluding studies with high risk
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of bias (eMethods 3 in the Supplement). Meta-regression analy-
ses were performed to examine the influence of participant
characteristics (age, primiparity, personal depression his-
tory, and personal psychiatric history) and risk of bias on the
pooled ORs. Publication bias was investigated by visual in-
spection of the funnel plot44 and the Peters test.37,45
Quality of Evidence
GRADE (Grading of Recommendations Assessment, Develop-
ment, and Evaluation) for prognostic studies was used to evalu-
ate the overall certainty of the findings.46 GRADE is a system-
atic approach to assess the certainty of evidence by assessing
5 domains: methodological flaws of the studies (eg, risk of bias),
heterogeneity of results across studies (eg, inconsistency),
generalizability of the findings (eg, indirectness), precision of
the estimates, and risk of publication bias.46 The certainty in
the overall estimate can be rated in 4 categories, ranging from
high to very low.
Results
Search Results
The database search retrieved 4239 articles, of which 1122 were
excluded as duplicates and 2921 were excluded after the title
and abstract screening. Of the 196 articles left for full-text
screening, 178 did not meet our inclusion criteria (disagree-
ment in 8 of 196 screened articles; interrater reliability, 95.9%),
deeming 18 of the retrieved articles eligible for inclusion.47-64
An additional 7 articles were included through citation and ref-
erence search,65-71 and 1 article was included after updating
the database search72 (Figure 1). Authors of 21 articles with
insufficient data to estimate an OR were contacted, of which
1 author provided sufficient information on participant
distribution.58 In total, we included 26 articles.47-72
Study Characteristics
Study characteristics and risk of bias scores of the 26 included
articles are presented in the Table. Geographically, the stud-
ies represented the following continents: Asia (n = 8), Austra-
lia (n = 2), Europe (n = 9), North America (n = 5), and South
America (n = 2). Sample sizes varied between 37 and 85 080
women, totaling 100 877 postpartum women from 24 cohort
studies and 2 case-control studies. Family history of psychiat-
ric disorders was primarily assessed using self-reported ques-
tionnaires (n = 23), and PPD was assessed using validated in-
struments (n = 13), clinical interviews (n = 12), and nationwide
registers (n = 1). PPD was assessed from 1 to 52 weeks’ post par-
tum, on average at 10 weeks’ post partum. Risk of bias scores
ranged from 2 to 9 (eMethods 3 in the Supplement).
Primary Analysis: Family History of Psychiatric Disorders
and PPD
Of the 26 included articles, 25 were included in the analyses,
as 2 studies had overlapping study samples and only one of
them was included in the analyses.58,67 The primary analysis
showed increased odds of PPD when having family history of
psychiatric disorders (OR, 2.08; 95% CI, 1.67-2.59; I2 = 57.14%)
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 Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression
Figure 1. PRISMA Flowchart of Study Selection
4239 Records identified from databases
2600 Embase 1122 Removed before screening
1132 PubMed (duplicate)
507 PsycINFO
3117 Records title/abstract screened 2921 Excluded
196 Full text screened 178 Excluded
72 Exposure
40 Not full article
18 Eligible records 34 Study design
10 Outcome
10 No risk estimate
6 Language
5 Participants/comparison
1 Not distinct reporting
26 Studies included in review
(Figure 2), corresponding to a relative risk of 1.79 (95% CI, 1.52-
2.09), assuming a 15% prevalence of PPD in the general
population.1,2
Secondary Analyses: Assessment Time Post Partum
and Definition of Family History of Psychiatric Disorders
and PPD
Although the OR point estimate for PPD was higher within the
first 12 weeks post partum (OR, 2.18; 95% CI, 1.69-2.81), it did
not differ statistically from PPD assessed between 13 to 26
weeks post partum (OR, 1.63; 95% CI, 1.18-2.25) and 27 to
52 weeks post partum (OR, 1.35; 95% CI, 0.74-2.49) (Figure 3).
The ORs for the association between PPD and family history
of psychiatric disorders seemed higher when family history of
psychiatric disorders was self-reported compared with when
ascertained through validated instruments or registries. How-
ever, as only few studies used validated instruments (n = 2)
and registries (n = 1), the accuracy of these results is limited
(eFigure 1 in the Supplement). Furthermore, stratification on
how PPD was assessed showed no difference in ORs for devel-
oping PPD between assessment with clinical interviews or
validated instruments (eFigure 2 in the Supplement).
Subgroup, Sensitivity, and Meta-regression Analysis
Overall, the results of the subgroup, sensitivity, and meta-
regression analyses were in line with the main findings. Stud-
ies with a selected sample (n = 10) seemed to have higher ORs
for developing PPD than studies using community-based popu-
lations (n = 13). However, the 95% CIs of these subgroups over-
lapped, thereby showing no significant difference between the
groups (eFigure 3 in the Supplement). Subgroup analysis by
country showed that studies performed in Europe had lower
ORs for developing PPD compared with those performed in Asia
(eFigure 4 in the Supplement).
Subgroup analyses of study design (eFigure 5 in the Supple-
ment) and cumulative vs point prevalence estimates (eFigure 6
in the Supplement) and sensitivity analyses of unadjusted vs
adjusted estimates (eFigures 7 and 8 in the Supplement) and
omitting studies with high risk of bias score (eFigure 9 in the
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Original Investigation Research
8 Records identified from other
methods
7 Citation and reference search
1 Updated database search
Supplement) did not alter the findings. Similarly, the meta-
regression analyses testing participant characteristics of age,
primiparity, personal depression or psychiatric history, and risk
of bias score did not influence the results (eFigures 10 to 14 in
the Supplement).
Publication Bias
Visual inspection of the funnel plot suggested the potential for
small study bias (Figure 4); however, the Peters test did not
confirm this. Furthermore, after removing small studies with
extreme results,57,68,70,72 the pooled OR was lower but not sta-
tistically significantly different from the primary analysis (1.78
[95% CI, 1.47-2.14] vs 2.08 [95% CI, 1.67-2.59]) (eFigures 15 and
16 in the Supplement), suggesting no impact of publication bias.
Quality of the Evidence
The overall certainty of the evidence, according to GRADE, was
deemed moderate for the association between family history
of psychiatric disorders and PPD. We downgraded the overall
certainty of evidence because of inconsistency of the esti-
mates (eTable in the Supplement).
Discussion
This systematic review and meta-analysis identified an al-
most doubled risk of developing PPD in mothers with family
history of psychiatric disorders compared with mothers with-
out. This is in contrast to several systematic and umbrella re-
views, compiling all risk factors.7-21 However, our findings are
supported through studies of heritability of psychiatric disor-
ders within, but especially outside, the postpartum period, in-
dicating family history of psychiatric disorders is a strong
risk factor for developing psychiatric episodes.28-35 This dis-
crepancy in support of our findings could be because of meth-
odological differences, as in our systematic review, we in-
cluded studies regardless of their primary aim conditional on
reporting a risk estimate for the association between family his-
tory of psychiatric disorders and PPD. Additionally, we also
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 Research Original Investigation Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression

Table. Characteristics of Included Studies

Administrative information Sample Methods

Quality,
Sample size Family psychiatry PPD PPD risk of bias
population, Sample Study assessment assessment assessment assessment
Source Location No. characteristics design method method post partum score
Abdollahi et al,47 Iran, Asia 1546 Community-based Cohort Questionnaire Validated Cumulated 5
2014 (self-report) instrument 0-12 wk
(EPDS)
Boyce and Australia 425 Community-based Cohort Questionnaire Clinical Cumulative 8
Hickey,65 (self-report) interview 0-24 wk
2005 (SCID-IV)
Çankaya,66 2020 Turkey, Asia 245 Community-based Cohort Questionnaire Validated Between 4
(self-report) instrument 6-8 wk
(EPDS)
Chee et al,48 Singapore, 278 Community-based Cohort Questionnaire Clinical 6 wk 6
2005 Asia (self-report) interview
(SCID-IV)
Corwin et al,49 US, North 152 Selected group Cohort Questionnaire Validated Cumulated 2
2015 America (self-report) instrument 0-6 mo
(EPDS)
Dasgupta et al,72 India, Asia 72 Selected group Cohort Questionnaire Validated 1 wk 4
2021 (self-report) instrument
(EPDS)
Dennis and Canada, 569 (1 wk); Community-based Cohort Questionnaire Validated 1 wk and 3
Ross,50 North 487 (8 wk) (self-report) instrument 8 wk
2006 America (EPDS)
English et al,51 UK, Europe 480 NA Cohort Questionnaire Validated Between 2
2018 (self-report) instrument 6-10 wk
(EPDS)
Gausia et al,52 Bangladesh, 346 Community-based Cohort Questionnaire Validated Between 5
2009 Asia (self-report) instrument 6-8 wk
(EPDS)
Guintivano US, North 1517 Selected group Case-control Questionnaire Clinical 6 wk 4
et al,53 2018 America (self-report) interview
(MINI+)
Johnstone Australia 490 Community-based Cohort Questionnaire Validated 8 wk 3
et al,54 2001 (self-report) instrument
(EPDS)
Kimmel et al,55 US, North 37 Selected group Cohort Questionnaire Clinical 1 mo 3
2015 America (self-report) interview
(SCID-IV)
Kirpinar et al,56 Turkey, Asia 479 Community-based Cohort Questionnaire Validated 6 wk 4
2010 (self-report) instrument
(EPDS)
Lin et al,57 Taiwan, Asia 234 Selected group Cohort Questionnaire Clinical 4 wk 5
2019 (self-report) interview
(MINI+)
Nielsen Forman Denmark, 3546 Community-based Cohort Questionnaire Validated 4 mo 6
et al,67 2000 Europea (self-report) instrument
(EPDS)
Meltzer-Brody Denmark, 85 080 Population-based Cohort Registers Register 0-6 mo 9
et al,58 2018 Europeb
O’Hara,68 US, North 99 Selected group Cohort Questionnaire Clinical 9 wk 4
1986 America (self-report) interview
(SADS)
Pham et al,59 Argentina, 539 Selected group Cohort Questionnaire Validated 4 wk 3
2018 South (self-report) instrument
America (EPDS)
Pop et al,69 The 293 Community-based Cohort Questionnaire Clinical 4 wk 6
1995 Netherlands, (self-report) interview
Europe (RDC)
Radoš et al,71 Croatia, 272 Community-based Cohort Questionnaire Clinical 6 wk 5
2013 Europe (self-report) interview
(SCID-IV)
Rambelli et al,60 Italy, 600 Community-based Cohort Validated Clinical 6 mo 7
2010 Europe instrument (FHS) interview
(SCID-IV)
Saldanha et al,70 India, Asia 186 Selected group Cohort Questionnaire Validated Cumulated 5
2014 (self-report) instrument 0-6 wk
(EPDS)

(continued)

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 Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression Original Investigation Research

Table. Characteristics of Included Studies (continued)

Administrative information Sample Methods

Quality,
Sample size Family psychiatry PPD PPD risk of bias
population, Sample Study assessment assessment assessment assessment
Source Location No. characteristics design method method post partum score
Silva et al,61 Brazil, 810 Selected group Cohort Questionnaire Validated Between 3
2012 South (self-report) instrument 30-60 d
America (EPDS)
Stickel et al,62 Germany, 196 Community-based Cohort Questionnaire Clinical 12 wk 5
2021 Europe (self-report) interview
(HDRS-17)
Tebeka et al,63 France, 2109 (2 mo); Selected group Case-control Validated Clinical 2 mo; 12 mo 7
2021 Europe 2094 (12 mo) instrument (FISC) interview
(DIGS)
Verkerk et al,64 The 277 (3, 6, and Community-based Cohort Questionnaire Clinical 3 mo; 6 mo; 6
2005 Netherlands, 12 mo) (self-report) interview 12 mo
Europe (RDC)
Abbreviations: DIGS, Diagnostic Interview for Genetic Studies; EPDS, Edinburgh Disorders and Schizophrenia; SCID-IV, Structured Clinical Interview for DSM-4.
Postnatal Depression Scale; FHS, Family History Screen; FISC, Family Informant a
Overlapping study sample with another included article; therefore, this was
Schedule and Criteria; HDRS-17, Hamilton Depression Rating Scale; not included in meta-analysis.
MINI+, Mini-International Neuropsychiatric Interview; PPD, postpartum b
Numbers were obtained from the authors.
depression; RDC, Research Diagnostic Criteria; SADS, Schedule for Affective

Figure 2. Primary Analysis

Study Odds ratio (95% CI) Decreased Increased Weight, %

O’Hara,68 1986 7.67 (2.07-28.34) 2.13
Pop et al,69 1995 2.30 (0.91-5.79) 3.42
Johnstone et al,54 2001 2.83 (1.30-6.18) 4.12
Boyce and Hickey,65 2005 0.83 (0.32-2.15) 3.30
Chee et al,48 2005 2.82 (0.31-25.46) 0.90
Verkerk et al,64 2005 1.60 (0.67-3.84) 3.64
Dennis and Ross,50 2006 1.67 (1.14-2.44) 6.82
Gausia et al,52 2009 1.60 (0.57-4.48) 2.98
Kirpinar et al,56 2010 2.03 (0.78-5.30) 3.27
Rambelli et al,60 2010 2.10 (1.03-4.28) 4.52
Silva et al,61 2010 1.17 (0.70-1.96) 5.84
Rados̆ et al,71 2013 0.99 (0.22-4.49) 1.69
Abdollahi et al,47 2014 1.79 (1.10-2.91) 6.04
Saldanha et al,70 2014 5.75 (2.09-15.79) 3.05
Corwin et al,49 2015 3.13 (1.32-7.42) 3.69
Kimmel et al,55 2015 0.64 (0.15-2.68) 1.84
English et al,51 2018 1.53 (0.89-2.62) 5.66
Guintivano et al,53 2018 3.74 (2.52-5.55) 6.71
Meltzer-Brody et al,58 2018 1.52 (0.93-2.47) 6.04
Pham et al,59 2018 1.99 (1.02-3.91) 4.75
Lin et al,57 2019 7.50 (2.72-20.71) 3.03
Çankaya,66 2020 2.45 (0.79-7.56) 2.64
Stickel et al,62 2021 1.89 (0.82-4.39) 3.81
Tebeka et al,63 2021 1.30 (1.00-1.69) 7.61
Dasgupta et al,72 2021 10.67 (3.32-34.24) 2.51
Overall 2.08 (1.67-2.59)
Heterogeneity: τ2 = 0.15; I2 = 57.14%; H2 = 2.33
Test of θj = θj: Q(24) = 57.88; P < .001 0.0625 0.25 1 4 16 64 Pooled association between family
Test of θ = 0: z = 6.51; P < .001 Odds ratio (95% CI) history of psychiatric disorders and
postpartum depression.

included studies if they reported sufficient information for us
to calculate this estimate, which led to inclusion of 12 addi-
tional studies based on this criterion.49,55-58,61,62,66,68,70-72 In
contrast, in some systematic reviews, it is not clear whether
such an inclusion criterion was applied,7-10,14-18 and no meta-
analysis was performed.9,15-18 Few reviews focused on the gen-
eral population as we did,7-9,14 and among them, some had pre-
specified risk factors or themes of interest.8,9 Others were based
on more selected populations 11,15-18 or country-specific
populations.10,12,13 Some excluded high-risk populations,10,14,15
and some were primarily investigating PPD prevalence and only
secondarily investigating risk factors for PPD, which was re-
flected in their literature search.12,16-18
It is outside the scope of this review to investigate why fam-
ily history of psychiatric disorders is a risk factor for PPD, but
it is most likely due to both genetic and environmental factors

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 Research Original Investigation Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression

Figure 3. Stratified Analysis by Postpartum Depression Assessment Time

Study Odds ratio (95% CI) Decreased Increased Weight, %

0-12 wk Post partum
O’Hara,68 1986 7.67 (2.07-28.34) 1.80
Pop et al,69 1995 2.30 (0.91-5.79) 2.94
Johnstone et al,54 2001 2.83 (1.30-6.18) 3.59
Chee et al,48 2005 2.82 (0.31-25.46) 0.74
Verkerk et al,64 2005 1.60 (0.67-3.84) 3.15
Dennis and Ross,50 2006 1.67 (1.14-2.44) 6.20
Gausia et al,52 2009 1.60 (0.57-4.48) 2.55
Kirpinar et al,56 2010 2.03 (0.78-5.30) 2.81
Silva et al,61 2010 1.17 (0.70-1.96) 5.23
Rados̆ et al,71 2013 0.99 (0.22-4.49) 1.42
Abdollahi et al,47 2014 1.79 (1.10-2.91) 5.42
Saldanha et al,70 2014 5.75 (2.09-15.79) 2.61
Kimmel et al,55 2015 0.64 (0.15-2.68) 1.55
English et al,51 2018 1.53 (0.89-2.62) 5.05
Guintivano et al,53 2018 3.74 (2.52-5.55) 6.10
Pham et al,59 2018 1.99 (1.02-3.91) 4.18
Lin et al,57 2019 7.50 (2.72-20.71) 2.60
Çankaya,66 2020 2.45 (0.79-7.56) 2.24
Stickel et al,62 2021 1.89 (0.82-4.39) 3.30
Tebeka et al,63 2021 1.30 (1.00-1.69) 7.02
Dasgupta et al,72 2021 10.67 (3.32-34.24) 2.13
Heterogeneity: τ2 = 0.18; 2.18 (1.69-2.81)
I2 = 61.60%; H2 = 2.60
13-26 wk Post partum
Boyce and Hickey,65 2005 0.83 (0.32-2.15) 2.83
Verkerk et al,64 2005 1.19 (0.45-3.14) 2.76
Rambelli et al,60 2010 2.10 (1.03-4.28) 3.96
Corwin et al,49 2015 3.13 (1.32-7.42) 3.20
Meltzer-Brody et al,58 2018 1.52 (0.93-2.47) 5.43
Heterogeneity: τ2 = 0; 1.63 (1.18-2.25)
I2 = 0%; H2 = 1.00
27-52 wk Post partum
Verkerk et al,64 2005 0.76 (0.25-2.33) 2.26
Tebeka et al,63 2021 1.60 (1.21-2.12) 6.92
Heterogeneity: τ2 = 0.10; 1.35 (0.74-2.49)
I2 = 37.37%; H2 = 1.60
0.0625 0.25 1 4 16 64
Odds ratio (95% CI)

explanation is supported by umbrella reviews concluding that

Figure 4. Funnel Plot
lack of social support is a significant PPD risk factor.19,20
0
Pseudo 95% CI Implications of Findings
Estimated θIV Family history of psychiatric disorders was assessed with
Studies
self-report in most studies (n = 23), which indicates potential
Standard error

0.5
benefits of using a single self-reported question on family
history of psychiatric disorders in routine perinatal care
when trying to identify high-risk women. Adding to this,
personal psychiatric history is another strong PPD risk
1 factor.19,20 Jointly, this suggests the potential for a quick and
low-cost assessment of PPD risk in clinical practice using only
–2 –1 0 1 2 3 2 self-reported questions: history of personal and family psy-
Effect size
chiatric disorders. As the assessment is possible even prior to
conception, this would leave time for planning preventive
during upbringing and later in life, as suggested for psychiatric efforts, eg, psychosocial and psychological interventions
disorders outside the postpartum period.73 Growing up in an targeting these at-risk women.74
environment with parents struggling with mental health prob- It is beyond the reach of this review to suggest actionable
lems potentially influences the social support received from clinical implications, but next steps could focus on how and
these parents when going into motherhood. This particular when to screen for family history of psychiatric disorders while

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 Family History of Psychiatric Disorders as a Risk Factor for Maternal Postpartum Depression Original Investigation Research

also considering how these screening questions will fit with
existing screening practices. Our findings are relevant to con-
sider moving forward and could inform selective prevention
efforts targeting women with a family history of psychiatric
disorders. These steps will assist identification of women at
risk of PPD but will need to do this in a way that would allow
appropriate allocation of scarce resources.
Strengths and Limitations
Our systematic review has several strengths, including align-
ment with the originally published protocol,40 stringent search
string, and screening, extraction, and assessment of included
studies done independently by 2 reviewers, all of which re-
duce reporting bias and increase validity.37 However, there are
also limitations. Family history of psychiatric disorders was
measured through self-report in most of the included studies
(n = 23). Phrasing of the self-reported question was very di-
verse and inconsistent: only 7 studies asked specifically about
first-degree family members50,53,54,63,64,68,69 and 10 studies
asked about specific diagnosis,47,49-51,53-55,64,68,69 covering
diagnosis from mild affective disorders to more intrusive dis-
orders, such as schizophrenia. This prevents us from investi-
gating how the type of specific diagnosis or family members
affect the risk of developing PPD, and we are unable to make
conclusion about specificity of the question. Furthermore,
self-report of psychiatric disorders often leads to underre-
porting in terms of social desirability bias because of, eg, risk
of stigma.75 The potential underreporting of family history
of psychiatric disorders would have led to misclassification;
therefore, the true association potentially could be even
stronger.
Our inclusion criteria related to language were articles in
English, Danish, Norwegian, Swedish, and Italian, which led
to exclusion of 6 articles in other languages in the full-text
screening. This constitutes only a small part of the excluded
articles (n = 178), which is unlikely to have led to consider-
able bias. We included only peer-reviewed studies. However,
the funnel plot did not reveal considerable small-study bi-
ases, and a subgroup analysis removing 4 studies with small
samples and extreme results did not alter the overall finding.
Conclusions
Based on 26 studies from 18 countries representing 5 conti-
nents, this systematic review and meta-analysis highlights
mothers with a family history of any psychiatric disorder
have an almost doubled risk of developing PPD compared
with mothers without. Information on family history of psy-
chiatric disorders is easy to identify through simple self-
reported question(s), potentially as part of routine perinatal
care, and early identification makes timely and targeted
intervention possible to prevent PPD or mitigate the conse-
quences thereof.

ARTICLE INFORMATION
Accepted for Publication: June 28, 2022.
Published Online: August 17, 2022.
doi:10.1001/jamapsychiatry.2022.2400
Author Affiliations: National Centre for
Register-based Research, Aarhus University,
Aarhus, Denmark (Zacher Kjeldsen, Liu, Madsen,
Munk-Olsen); Department of Public Health, Aarhus
University, Aarhus, Denmark (Zacher Kjeldsen);
Research Unit for Musculoskeletal Function and
Physiotherapy, Department of Sports Science and
Clinical Biomechanics, University of Southern
Denmark, Odense, Denmark (Bricca); The Research
Unit PROgrez, Department of Physiotherapy and
Occupational Therapy, Næstved-Slagelse-Ringsted
Hospitals, Slagelse, Denmark (Bricca);
Neurobiology Research Unit, Copenhagen
University Hospital–Rigshospitalet, Copenhagen,
Denmark (Frokjaer); Mental Health Services,
Capital Region of Denmark, Copenhagen, Denmark
(Frokjaer); Faculty of Health and Medical Sciences,
University of Copenhagen, Copenhagen, Denmark
(Frokjaer); Department of Clinical Research,
University of Southern Denmark, Odense,
Denmark (Munk-Olsen).
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Zacher Kjeldsen, Bricca,
Frokjaer.
Obtained funding: Munk-Olsen.
Study supervision: Liu, Frokjaer, Madsen,
Munk-Olsen.
Conflict of Interest Disclosures: Dr Frokjaer has
served as consultant and lecturer for H. Lundbeck
and Sage Therapeutics. No other disclosures
were reported.
Funding/Support: Ms Zacher Kjeldsen is
supported by The Lundbeck Foundation
(R313-2019-569). Dr Bricca is a postdoctoral
researcher in the MOBILIZE project funded by
the European Research Council under the
European Union’s Horizon 2020 Research and
Innovation Programme (grant agreement 801790).
Dr Liu is supported by the European Union’s
Horizon 2020 Research and Innovation
Programme under the Marie Sklodowska-Curie
(grant agreement 891079). Dr Munk-Olsen has
received support from The Lundbeck Foundation
(R313-2019-569).
Role of the Funder/Sponsor: The funders had no
Obstet Gynecol. 2005;106(5 pt 1):1071-1083.
doi:10.1097/01.AOG.0000183597.31630.db
2. O’Hara MW, McCabe JE. Postpartum depression:
current status and future directions. Annu Rev Clin
Psychol. 2013;9:379-407. doi:10.1146/annurev-
clinpsy-050212-185612
3. Stewart DE, Vigod SN. Postpartum depression:
pathophysiology, treatment, and emerging
therapeutics. Annu Rev Med. 2019;70:183-196.
doi:10.1146/annurev-med-041217-011106
4. Sockol LE. A systematic review of the efficacy
of cognitive behavioral therapy for treating and
preventing perinatal depression. J Affect Disord.
2015;177:7-21. doi:10.1016/j.jad.2015.01.052
5. O’Connor E, Senger CA, Henninger ML,
Coppola E, Gaynes BN. Interventions to prevent
perinatal depression: evidence report and
systematic review for the US Preventive Services
Task Force. JAMA. 2019;321(6):588-601.
doi:10.1001/jama.2018.20865
6. Brown JVE, Wilson CA, Ayre K, et al.
Antidepressant treatment for postnatal depression.
Cochrane Database Syst Rev. 2021;(2):CD013560.
doi:10.1002/14651858.CD013560.pub2

Author Contributions: Dr Zacher Kjeldsen had full
access to all of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis. Drs Madsen and
Munk-Olsen are co–last authors.
Study concept and design: Zacher Kjeldsen, Bricca,
Frokjaer, Madsen, Munk-Olsen.
Acquisition, analysis, or interpretation of data:
All authors.
Drafting of the manuscript: Zacher Kjeldsen.
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review,
or approval of the manuscript; and decision to
submit the manuscript for publication.
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