Is a Family History of Bipolar Disorder Put You at Higher Risk for Postpartum Depression

Am J Psychiatry. Writer manuscript; bachelor in PMC 2019 Aug 1.

Published in final edited form equally:

PMCID: PMC6070397

NIHMSID: NIHMS941324

Familiality of psychiatric disorders and adventure of postpartum psychiatric episodes: A population-based cohort study

Anna East. Bauer, Ph.D.,^one Merete L. Maegbaek, K.Sc.,^two Xiaoqin Liu, Ph.D.,² Naomi R. Wray, Ph.D.,^{3, four} Patrick F. Sullivan, Yard.D.,^{i, 5} William C. Miller, M.D.,^vi Samantha Meltzer-Brody, M.D.,^{one, *} and Trine Munk-Olsen, Ph.D.^{2, *}

Anna Due east. Bauer

¹Department of Psychiatry, University of North Carolina School of Medicine, Chapel Loma, NC, United states

Merete L. Maegbaek

²National Eye for Annals-Based Research, Aarhus University, Aarhus, Kingdom of denmark

Xiaoqin Liu

²National Centre for Register-Based Inquiry, Aarhus University, Aarhus, Denmark

Naomi R. Wray

³Institute for Molecular Bioscience, The University of Queensland, Brisbane, Commonwealth of australia

^ivQueensland Brain Institute, The University of Queensland, Brisbane, Commonwealth of australia

Patrick F. Sullivan

¹Department of Psychiatry, University of North Carolina Schoolhouse of Medicine, Chapel Hill, NC, U.s.

⁵Department of Genetics, Academy of Northward Carolina School of Medicine, Chapel Colina, NC, United states

William C. Miller

^sixOhio State University College of Public Health, Columbus, OH, Usa

Samantha Meltzer-Brody

¹Department of Psychiatry, Academy of North Carolina Schoolhouse of Medicine, Chapel Hill, NC, USA

Trine Munk-Olsen

^twoNational Center for Register-Based Enquiry, Aarhus University, Aarhus, Denmark

Abstract

Objective

Postpartum psychiatric disorders are common and morbid complications of pregnancy. Nosotros sought to evaluate how family history of psychiatric disorders is associated with postpartum psychiatric disorders in proband mothers with and without a prior psychiatric history by assessing degree of relationship, type of disorder, and sex of family members.

Method

We linked Danish birth and psychiatric treatment registers to evaluate familial risk of postpartum psychiatric episodes in a national, population-based cohort. Probands were first-time mothers who gave nascence later historic period xv years and before December 31, 2012 who were born in Denmark in 1970 or later on (northward=362,462). The primary exposure was a diagnosed psychiatric disorder in a relative. We used Cox regression models to estimate the hazard ratio (HR) of postpartum psychiatric disorders in proband mothers.

Results

Relative adventure of psychiatric disorders in the postpartum period was elevated when get-go-degree family members had a psychiatric disorder (HR 1.45; 95% CI 1.28–one.65) and highest when proband mothers had a first-caste family fellow member with bipolar disorder (HR 2.86; 95% CI, ane.88–iv.35). Associations were stronger among proband mothers with no previous psychiatric history. There were no notable differences by sex of the family unit member.

Conclusions

Family history of psychiatric disorders, especially bipolar disorder, is an important run a risk cistron for postpartum psychiatric disorders. To aid identification of women at-risk for postpartum psychiatric disorders, questions related to female and male person first-caste relatives with bipolar disorder is of the highest importance, and should be added to routine clinical screening guidelines to improve prediction of chance.

Introduction

The postpartum period is a vulnerable time for onset of psychiatric disorders, existence 1 of the few identified periods of heightened risk throughout the life class (i–3). Prior history of a psychiatric disorder, occurring either within or outside of the perinatal menstruation, increases run a risk of experiencing a postpartum psychiatric disorder (3–8). Although personal psychiatric history is a highly predictive chance factor for postpartum psychiatric disorders, predicting who will experience a new-onset psychiatric disorder in the postpartum menstruum remains a meaning claiming.

Family unit psychiatric history is a strong and consistent risk factor for psychiatric disorders outside of the perinatal menstruation (8, 9). Perinatal mood disorders may be more heritable than other mood disorders, as the heritability for perinatal low is estimated to be 44% (xi) compared with 37% for major depressive disorder (11, 12). Heritability of other types of perinatal psychiatric disorders is unknown. Family history of a postpartum mood disorder in a female parent or sister doubles or triples risk of experiencing a postpartum mood disorder (14–16), and postpartum psychosis in a female parent or sis increases risk of postpartum psychosis five-fold (14). Family unit history of non-postpartum mood disorders is also associated with postpartum mood disorders, especially for bipolar disorder and the most severe postpartum episodes like postpartum psychosis (14,16–19). These prior studies, however, accept primarily been conducted in high-hazard populations of women and their families with previously diagnosed psychiatric disorders. In that location is much less known nearly how familiality of psychiatric disorders outside of the perinatal catamenia influence postpartum psychiatric disorders for the broader spectrum of psychiatric disorders, particularly in women without a personal psychiatric history. The few existing population-based studies examining the clan betwixt family history of non-postpartum mood disorders with postpartum mood disorders have not investigated specific types of psychiatric disorders among unlike degrees of familial relationships (iii, xix).

Prior work has non explored whether the familial associations of postpartum psychiatric disorders are related to a specific female vulnerability (east.1000. female parent to daughter). Because previous studies of familiality of postpartum psychiatric disorders have primarily evaluated the relationship betwixt postpartum mood disorders in proband mothers and postpartum mood disorders in first-caste relatives, most have exclusively evaluated pairs of female relatives (e.thou., mother-girl or sister-sister pairs) (11,14–sixteen,21,22). Among studies including both male person and female relatives with psychiatric disorders outside of the perinatal period, none have evaluated the difference in recurrence risk amongst female relatives compared to male relatives (eleven,17). Agreement the degree to which familial history of psychiatric disorders predicts risk for postpartum psychiatric disorders would essentially aid our ability to place those at greatest hazard for postpartum psychiatric disorders and arbitrate early.

Nosotros aimed to address this gap in the literature by evaluating how family unit history of psychiatric disorders influences take chances for postpartum psychiatric episodes. We wanted to evaluate whether familial risk of postpartum psychiatric disorders differs by degree of human relationship and sex of the family members in both women with and without a prior personal psychiatric history. To address these aims, nosotros conducted a population-based study of recurrence take a chance (the likelihood a trait in 1 family member will occur over again in another family member) (23–25), a study design frequently applied in psychiatric genetics (ten,fourteen,16,25,26). Recurrence hazard studies typically evaluate the same disorder in family members (e.1000. postpartum low in both a proband mother and her sister). In our study, nosotros sought to determine the unique familial contributions of psychiatric disorders exterior of the perinatal period to psychiatric events within the postpartum flow; thus, nosotros consider the recurrent event (a psychiatric diagnosis inside the postpartum period) to be different than the familial event (a psychiatric diagnosis at any time point). Nosotros refer to this specific type of recurrence risk as 'familial risk' from this point forward.

Methods

Study population

Nosotros conducted a population-based accomplice report inside the Danish Civil Registration Organization (27). A unique personal identifier of all people living in Kingdom of denmark enables comprehensive linkages with multiple health-related national registers as well as linkages to family unit members. Probands (time to come referred to as proband mothers) were selected from all women born in Denmark from 1970 onward with non-missing links to both parents (n=1,336,419). Proband mothers were all first-time mothers who gave birth to a live-born child when at least 15 years of historic period and earlier the end of follow-up on December 31, 2012. A total of 362,462 proband mothers were included in our study (Figure 1).

Identification of postpartum psychiatric episodes

Our issue of interest was a psychiatric episode diagnosis during the postpartum menstruum in proband mothers. Information on psychiatric episodes was obtained from the Psychiatric Central Register (28), which provides information on inpatient handling since 1969 and outpatient treatment since 1995. Outpatient diagnoses come from specialty psychiatric clinics and practise not include diagnoses from primary care settings. Diagnoses are recorded using International Nomenclature of Disease (ICD) codes (ICD-viii prior to 1994 and ICD-10 codes 1994 and later on). We defined a postpartum psychiatric disorder as a treated psychiatric episode (290–315 in ICD-eight codes and F00–F99 in ICD-10 codes), excluding organic mental disorders (290.09, 290.ten, 290.xi,290.18, 290.19, 292.X9, 293.X9, 294.X9, and 309.X9 in ICD-8 codes; F00–F09 in ICD-x codes), substance abuse (291.X9, 294.39, 303.X9, 303.20,303.28, 303.90 and 304.X9 in ICD-8 codes and F10–nineteen in ICD-10 codes), and mental retardation (310–315 in ICD-8 codes; F70–F79 in ICD-ten codes), which have been well-validated in these registries (28,29). For our primary assay, we considered the postpartum flow to be 0 to 6 months after childbirth. Prior work in our data have indicated increasing vulnerability for depressive episodes up to 6 months after childbirth (two) and nosotros wanted to ensure we deemed for a potential delay between symptom onset and recorded diagnosis. In sensitivity analyses, we also examined two other fourth dimension periods separately: one) 0 to three months postpartum, a more narrowly defined and maybe more etiologically similar phenotype (30–32), and 2) 0 to 12 months postpartum, an increasingly applied clinical definition for the postpartum period (30,33,34).

Identification of relatives of proband mothers and family history of psychiatric episodes

To identify relatives, proband mothers were linked to their parents by unique identifier and subsequent family relationships were identified through these linkages. The caste of relationship of family members was divers every bit follows: Beginning-degree relatives included mother, father, and full sibling; Second-degree relatives included grandparents, half-siblings, uncles, and aunts; Third-degree relatives included cousins. Because the register was established in 1970, we were unable to place people built-in before this date, and thus, second- and third-degree relationships are less consummate.

Among the proband mothers included in our study population, we considered the association betwixt a postpartum psychiatric disorder and whatever psychiatric disorder in our categorized relatives. Furthermore, we investigated specifically five hierarchical diagnostic groups of psychiatric disorders in the relatives: 1) schizophrenia and related disorders (highest in hierarchy; ICD-10 codes F20–F29); 2) bipolar disorder (ICD-10 codes F30–31; 3) unipolar disorder (ICD-x codes F32–33; four) other mood disorders except for bipolar and unipolar disorders (ICD-10 codes F34–39); 5) other psychiatric disorders (lowest in hierarchy; ICD-x codes F40–F69 and F80–F99). This hierarchical arrangement is built into the ICD diagnostic system and accounts for individuals with more than one recorded diagnoses.

Statistical analysis

Nosotros started follow-upwards at the appointment of childbirth for each proband mother and followed her until a postpartum psychiatric episode, three, vi or 12 months postpartum, expiry, emigration, or December 31, 2012, whichever came get-go. Nosotros restricted proband mothers to commencement-time mothers for several reasons: 1) history of PPD increases risk in subsequent pregnancies, two) prior birth event may influence later on reproductive behavior, and 3) environmental factors during the postpartum flow are dissimilar after outset and subsequent births. To ensure that detection of a psychiatric diagnosis in a relative occurred before the postpartum psychiatric diagnosis and was non dependent on the proband mother's age at childbirth, we assessed whether the relatives had a diagnosis of psychiatric disorder on or prior to the proband mother'south 15^th altogether, going back to 1970. We adjusted for the calendar year and the proband mother'due south age at birth.

Nosotros evaluated the association by determining familial risk, a register-based estimate of the risk of experiencing a postpartum psychiatric disorder when a relative of a proband mother had a psychiatric disorder. We further examined the association of postpartum psychiatric disorders with each of the 5 hierarchical psychiatric disorders. We used Cox regression analysis to calculate run a risk ratios (HR). Given postpartum psychiatric disorders amidst proband mothers with a psychiatric history prior to childbirth may be a distinct psychiatric phenotype, we examined the associations in proband mothers with and without previous psychiatric history separately.

To guess whether the associations betwixt family unit history of psychiatric disorders and postpartum psychiatric disorders were due to a genetic contribution or shared environmental factors, we repeated the analyses by outset-, 2nd-, and tertiary-degree relatives and sex of the relatives with a psychiatric disorder. If an increased risk is due to familial factors attributable to not-genetic factors shared by nuclear families, nosotros would expect to encounter excess risk only among first-caste relatives. Conversely, if the increased risk is due to a genetic contribution in some extent, we would wait to see backlog among both close and afar relatives in line with their coefficient of relationship.

Statistical analyses were performed using the statistical software packet Stata 13.ane.

Results

The final population-based cohort consisted of 362,462 proband mothers who gave nascence to their first child in Denmark betwixt 1985 and 2012. Mean (SD) historic period of proband mothers was 27.0 (iv.3) years at the time of delivery. Of these mothers, 2,603 (0.7%) experienced a psychiatric disorder within 6 months postpartum and 4,085 (1.ane%) within 12 months postpartum (Table 1).

Tabular array ane

Characteristics of the study population for women with psychiatric episodes within 6 months and 12 months postpartum.

Total proband mothers (N=362,462)	Probands with no prior psychiatric history (N=339,112)				Probands with prior psychiatric history (N=23,350)
	Postpartum episodes within				Postpartum episodes within
	half dozen months		12 months		vi months		12 months
	Due north	%	N	%	North	%	N	%
N	ane,585		2,421		ane,018		1,664
Age at starting time childbirth
Mean (SD) (years)	27.0	4.3	26.v	4.6	26.7	4.7	26.3	4.seven
Birth twelvemonth of proband mother
1985–1994	35	2.ii	73	three.0	12	1.2	16	1.0
1995–1999	254	sixteen.0	391	16.2	99	9.seven	151	9.1
2000–2004	392	24.7	619	25.6	203	19.nine	343	20.6
2005–2009	588	37.1	902	37.3	438	43.0	709	42.half-dozen
2010–2012	316	19.9	436	18.0	266	26.1	445	26.7
Previous psychiatric history amongst parents
Any psychiatric diagnosis, female parent	lxx	4.4	109	4.5	84	8.three	145	8.7
Any psychiatric diagnosis, father	57	3.6	85	3.5	51	v.0	88	v.3
Any psychiatric diagnosis, first-degree	132	8.three	203	eight.iv	141	xiii.9	244	fourteen.seven
Any psychiatric diagnosis, 2d-degree	173	10.9	281	eleven.vi	163	16.0	294	17.7
Whatsoever psychiatric diagnosis, 3rd-degree	47	iii.0	76	iii.1	49	4.8	97	5.8
Schizophrenia, first-degree	43	2.7	60	2.5	46	iv.5	65	3.9
Schizophrenia, 2d-degree	58	three.seven	91	three.viii	45	4.4	78	iv.vii
Schizophrenia, third-degree	eight	0.v	11	0.five	seven	0.vii	11	0.7
Bipolar disorder, showtime-degree	xiii	0.8	18	0.7	9	0.nine	14	0.8
Bipolar disorder, 2d-caste	vii	0.4	thirteen	0.5	eight	0.8	10	0.half-dozen
Bipolar disorder, 3rd-caste	0	0	<4		0	0	0	0
Unipolar disorder, first-degree	50	iii.two	81	3.3	46	4.5	83	5.0
Unipolar disorder, 2nd-degree	73	iv.vi	118	4.9	66	6.5	125	7.5
Unipolar disorder, third-degree	<4		5	0.2	vi	0.6	12	0.vii
Other mood disorders, first-caste	9	0.vi	12	0.five	4	0.4	fourteen	0.8
Other mood disorders, second-degree	4	0.3	fourteen	0.6	6	0.6	xi	0.7
Other mood disorders, third-degree	0	0	0	0	0	0	<4
Other psychiatric disorders, first-degree	21	1.iii	41	1.vii	43	iv.2	81	4.9
Other psychiatric disorders, second-degree	57	3.half dozen	103	four.3	68	6.7	125	7.5
Other psychiatric disorders, 3rd-degree	37	2.3	62	2.6	xl	3.ix	81	four.nine

Equally described, we evaluated familial hazard, a register-based gauge of the gamble of experiencing a postpartum psychiatric disorder when a relative of a proband female parent had a psychiatric disorder. Results are presented for familial risk of postpartum psychiatric episodes within 6 months postpartum, but results were similar for 0 to three months and 0 to 12 months postpartum (Table S1 and S2). Overall, the chance of experiencing a psychiatric disorder inside the kickoff six months postpartum was higher among proband mothers with a kickoff-degree relative who had experienced any psychiatric disorder compared with proband mothers whose relatives did non experience any psychiatric disorder (HR i.45; 95% CI 1.28–ane.65). The hazard ratio of experiencing a postpartum psychiatric episode was the highest when proband mothers had a first-degree relative with bipolar disorder (60 minutes 2.86; 95% CI, 1.88–four.35). Familial hazard was also elevated for those who had a start-degree relative with schizophrenia (HR 1.58; 95% CI 1.27–one.95), unipolar disorder (Hour 1.52; 95% CI 1.24–one.87), or other mood disorder (HR 1.78; 95% CI ane.03–3.06), just not other psychiatric disorders (Hr 0.ninety; 95% CI 0.70–ane.16). The point estimates tended to be larger among proband mothers with no previous psychiatric history (Table 2, Effigy 2). We found that prior psychiatric history was a strong take chances factor for postpartum psychiatric disorders (HR 8.66; 95% CI 7.97–nine.40, for postpartum disorders in women with prior psychiatric history compared to women with no psychiatric history, adjusted for psychiatric disorders in first, second, and third degree relatives).

Familial risk of psychiatric episodes inside half dozen months postpartum in proband mothers with and without personal psychiatric history, by blazon of disorder and sex activity in relatives.

Tabular array 2

Familial take chances of psychiatric disorders inside six months postpartum, by type of disorder of the proband mother's relative.

Relationship to probandnew mother	Relatives with any psychiatric vs. no psychiatric disorders		Relatives with schizophrenia vs. no schizophrenia		Relatives with bipolar disorder vs. no bipolar disorder		Relatives with unipolar disorder vs. no unipolar disorder		Relatives with other mood disorder vs. no other mood disorder		Relatives with other psychiatric disorders vs. no other psychiatric disorders
	Hr	95% CI	Hr	95% CI	HR	95% CI	Hour	95% CI	60 minutes	95% CI	HR	95% CI
All proband mothers a
Mother	i.50	1.27–ane.77	one.58	i.xix–two.10	2.43	1.34–4.39	1.58	1.21–2.05	1.82	0.81–iv.05	1.02	0.71–1.46
Father	1.54	i.27–1.87	ane.66	ane.20–2.30	3.47	one.87–6.46	one.52	one.10–2.10	1.87	0.89–iii.92	0.92	0.56–1.51
Whatsoever get-go-degree relative	1.45	one.28–1.65	1.58	i.27–1.95	2.86	one.88–4.35	i.52	ane.24–i.87	one.78	1.03–iii.06	0.90	0.lxx–1.16
Any second-degree relative	one.sixteen	1.02–i.31	1.09	0.89–ane.33	1.11	0.67–1.84	1.15	0.97–1.37	1.01	0.54–1.88	i.sixteen	0.96–1.41
Any third-degree relative	1.27	i.03–1.58	ii.xv	1.29–3.58	-	-	1.39	0.72–2.68	-	-	ane.sixteen	0.92–1.47
Proband mothers with no prior psychiatric history b
Mother	1.78	1.40–2.27	1.96	i.31–ii.93	3.53	one.68–7.42	1.56	i.04–ii.34	three.33	1.27–8.88	1.19	0.65–2.sixteen
Father	1.92	one.47–two.51	ane.54	0.93–2.57	3.99	ane.79–viii.89	two.xx	i.48–3.27	three.10	1.29–7.47	1.01	0.45–ii.26
Any first-degree relative	1.76	1.47–two.11	1.82	1.34–2.47	3.61	ii.09–6.23	1.85	1.39–2.45	three.ten	1.61–5.97	0.90	0.58–1.xl
Any 2d-caste relative	1.35	1.fourteen–one.threescore	1.35	1.04–1.76	0.98	0.47–2.07	i.30	ane.02–1.66	0.92	0.34–2.46	1.38	1.04–i.82
Any third-degree relative	1.46	1.08–1.98	two.68	one.33–5.39	-	-	ane.10	0.35–3.43	-	-	one.31	0.94–1.84
Proband mothers with prior psychiatric history b
Female parent	one.35	1.08–1.69	1.32	0.88–one.97	1.56	0.58–4.17	one.59	1.13–2.23	0.94	0.24–3.78	one.05	0.68–1.64
Father	1.28	0.97–1.70	1.74	1.14–ii.65	2.79	1.04–7.45	0.97	0.56–ane.67	0.90	0.22–three.60	0.96	0.51–1.80
Any first-degree relative	one.27	1.06–1.52	1.39	i.03–1.86	2.17	1.13–iv.18	1.28	0.95–1.73	0.89	0.33–2.36	0.99	0.72–1.36
Whatsoever second-degree relative	i.03	0.86–1.24	0.88	0.65–one.19	1.28	0.64–2.57	1.05	0.81–ane.36	1.12	0.50–ii.l	ane.11	0.85–one.44
Any tertiary-degree relative	1.21	0.90–i.64	one.91	0.90–4.03	-	-	1.76	0.78–three.95	-	-	1.13	0.81–ane.57

Familial run a risk of postpartum psychiatric disorders was elevated when first-degree relatives experienced psychiatric disorders, as described above, and slightly elevated for familial psychiatric disorders among more distant relatives (for any psychiatric disorder, second-degree relatives: Hour 1.sixteen; 95% CI i.02–one.31; tertiary-degree relatives: Hour ane.27; 95% CI 1.03–1.58). More distant relatives share both a reduced coefficient of relationship (Figure S1) and reduced shared family environment.

The familial risk of postpartum disorders in proband mothers born by mothers with psychiatric disorders (Hour one.50, 95% CI 1.27–i.77 for mothers) was similar to those born by fathers with psychiatric disorders (60 minutes i.54, 95% CI ane.27–1.87 for fathers). This pattern persisted for all five diagnostic groups of psychiatric disorders (Table 2). Likewise, when nosotros assessed familial hazard separately in female and male relatives more than generally, we did not observe differences by sex activity for either whatsoever psychiatric disorder or specific diagnostic groups of psychiatric disorders for any degree of human relationship (Tabular array 3, Figure 2).

Table 3

Familial risk of psychiatric disorders inside half dozen months postpartum, by blazon of disorder and sexual activity of first-degree relatives

Relationship to proband new female parent	Relatives with any psychiatric vs. no psychiatric disorders		Relatives with schizophrenia vs. no schizophrenia		Relatives with bipolar disorder vs. no bipolar disorder		Relatives with unipolar disorder vs. no unipolar disorder		Relatives with other mood disorder vs. no other mood disorder		Relatives with other psychiatric disorders vs. no other psychiatric disorders
	HR	95% CI	Hr	95% CI	HR	95% CI	HR	95% CI	Hr	95% CI	HR	95% CI
All proband mothers a
Whatever first-degree relative	1.45	i.28–1.65	1.58	one.27–i.95	2.86	1.88–four.35	1.52	1.24–1.87	1.78	1.03–3.06	0.xc	0.70–i.16
Female relative	1.36	ane.16–1.59	1.48	ane.thirteen–1.95	2.48	1.40–iv.37	1.51	ane.17–1.95	1.68	0.75–three.74	0.92	0.70–one.22
Male relative	one.32	i.eleven–1.57	1.52	1.12–2.06	three.45	1.91–6.23	1.45	1.07–ane.98	1.73	0.83–three.64	0.84	0.60–one.sixteen
Proband mothers with no prior psychiatric history b
Any first-degree relative	ane.76	1.47–2.11	i.82	1.34–2.47	3.61	2.09–six.23	1.85	1.39–2.45	iii.10	one.61–5.97	0.90	0.58–1.xl
Female relative	1.61	ane.27–ii.02	two.02	ane.xl–2.91	3.30	1.57–6.93	one.60	1.09–ii.36	3.07	1.fifteen–viii.18	0.95	0.58–i.54
Male relative	one.72	i.35–2.19	1.60	1.02–2.51	3.66	1.64–8.xvi	two.28	1.57–3.32	2.91	one.21–7.00	0.81	0.46–1.44
Proband mothers with prior psychiatric history b
Whatsoever outset-degree relative	1.27	ane.06–1.52	ane.39	1.03–ane.86	2.17	1.xiii–4.18	i.28	0.95–i.73	0.89	0.33–2.36	0.99	0.72–1.36
Female relative	one.24	1.01–1.53	ane.12	0.75–1.68	one.84	0.76–4.42	1.45	ane.03–2.05	0.87	0.22–three.50	one.01	0.71–1.43
Male relative	1.09	0.85–1.41	1.45	0.96–2.nineteen	3.14	i.30–7.56	0.83	0.48–1.44	0.83	0.21–iii.34	0.93	0.62–1.twoscore

Discussion

We used linked Danish birth and psychiatric registry data to determine familial take chances of postpartum psychiatric disorders associated with family history of psychiatric disorders within 5 hierarchical diagnostic groups. To our knowledge, this study is the first to use a large, population-based cohort to investigate familial run a risk of postpartum psychiatric disorders with psychiatric disorders outside of the perinatal period. Our analysis of first-always postpartum psychiatric disorders provides evidence of the importance of psychiatric disorders in family members even among women with no personal history of mental disease.

Our study is the beginning to address whether familial risk of postpartum psychiatric disorders differs by sex of the family member. Since only women may experience the consequence of a postpartum psychiatric disorder, prior studies of recurrence risk of postpartum psychiatric disorders have exclusively studied female-relative pairs (e.g., mother-daughter, sisters) (11,14–sixteen,21,22). However, both males and females feel non-postpartum psychiatric disorders, and it is unknown whether family history of not-postpartum psychiatric disorders experienced by male or female relatives differentially influences risk of postpartum psychiatric disorders. Studies of other psychiatric conditions (35) and small-scale studies of mood disorders in selected populations (36,37) have shown some bear witness of greater female heritability or transmission, just larger, population-based studies of psychiatric disorders have not plant sex differences (10,38). Consistent with this, nosotros establish that despite postpartum psychiatric disorders being uniquely female events, family history of psychiatric disorders in male relatives was just as influential as their occurrence in female relatives. Thus, when assessing risk for postpartum episodes, clinicians should enquire about family history of psychiatric disorders broadly, and not limit discussion only to postpartum psychiatric disorders or psychiatric disorders in female relatives.

We found that familial risk for postpartum psychiatric disorders was college for family history of bipolar disorder compared with family history of psychiatric disorders, which had previously merely been identified for the most severe postpartum psychiatric episodes (14,17) or among women with a personal history of mood disorders (14–17). Outside of the perinatal period, familial risk for bipolar disorder is greater than that of unipolar low (RR = 6.iv to vii.9 for bipolar disorder (10); RR = 2.eight for unipolar low (12)). We found similar patterns in our study of psychiatric disorders inside the postpartum period; familal gamble was higher with family history of bipolar disorder than for family history of unipolar depression (HR= 2.86, 95% CI 1.88–iv.35 for postpartum episodes with bipolar low; HR=1.52, 95% CI i.24–1.87 for postpartum episodes with unipolar depression). Our estimates, particularly for familial risk of postpartum disorders with familial bipolar disorder, were very similar to previous estimates for postpartum mood disorders overall (RR=2.3 to 3.ix) (xiv–16). It should be noted that previous recurrence risk studies of postpartum psychiatric disorders have all been conducted in cohorts of women with a prior psychiatric history, whereas we evaluated familial chance separately in women with and without prior psychiatric history. The link between bipolar disorder and postpartum psychosis is well established (half dozen,39–42), and recent work in these same information take shown an increase in the risk of conversion to bipolar disorder with closer time to birth of psychiatric encounter (18). Taken together with our findings demonstrating that family history of bipolar disorder is more than strongly associated with whatsoever postpartum psychiatric disorder and not only the nigh severe episodes, there is evidence for a genetic vulnerablity or other etiologically similar mechanisms linking bipolar disorder and psychiatric episodes specifically in the postpartum period and is supported by the literature (6,14,17,39–42).

Our analysis of a big, population-based cohort, provides the ability to investigate several types of psychiatric events and makes our results more generalizable to the broader population. Most prior studies of familiality of postpartum psychiatric disorders accept been conducted in modest cohorts or cohorts of high-risk women recruited specifically to study recurrent major depressive disorder and bipolar disorder. This report specifically captured psychiatric disorders in the postpartum period among proband mothers with and without prior psychiatric history. Prior studies typically accept not distinguished between incident episodes and those that may reverberate an ongoing psychiatric disorder that recurs during the postpartum period. Differentiating between new-onset episodes and recurrent episodes can have of import implications for both screening and handling. We also considered timing of onset of postpartum psychiatric episodes and separately analyzed 3 unlike fourth dimension periods: 0 to 3 months postpartum, 0 to 6 months postpartum, and 0 to 12 months postpartum. There is evidence that etiology of postpartum psychiatric disorders may differ by time of symptom onset (2,31,32,43), and that the commencement few weeks afterwards childbirth may be the well-nigh biologically vulnerable fourth dimension point (xxx,31). Even so, considering our information provide information nearly timing of diagnosis or handling, but not the onset of symptoms, there is likely a potential lag between onset of symptoms and when a mother seeks intendance. This is an intrinsic limitation in almost all studies of postpartum psychiatric disorders, and nosotros sought to address this limitation past analyzing the 0 to 6 calendar month fourth dimension menstruation. We also selected 0 to 12 months postpartum equally a clinically relevant time period (30,33,34). External ecology factors change during the first year postpartum, which may influence each time period differently. Despite the potential for differences, nosotros institute results of how family psychiatric history affects postpartum psychiatric disorders to be like across all three fourth dimension periods.

Use of registry data improves generalizability to broader populations, just there are also limitations to the data available in the registers. Our information included inpatient hospital admissions and outpatient psychiatric dispensary records, simply not records from full general practitioners. Rates of postpartum psychiatric disorders were lower compared to typically reported rates because cases were patients who obtained psychiatric care in a specialty dispensary or hospital, which captured the nigh astringent psychiatric episodes but not patients seeking care from their primary care provider. Therefore, these results are virtually generalizable to development of severe postpartum psychiatric disorders, and potentially not for postpartum psychiatric disorders overall. Additionally, because outpatient diagnoses were not included in the registers until 1995, psychiatric diagnoses prior to 1995 include just the near severe inpatient hospitalizations. To business relationship for the secular trends, we adjusted for calender year of the proband mothers and age at first delivery in the models. Moreover, to assess how this differentially defined exposure may influence our results, we repeated our analyses in a restricted cohort of only mothers who had children born afterwards 1995. Like trend was observed in this sub-analysis, although the interval estimates became wider and less precise due to small numbers of cases. We also acknowledge that our results are only generalizable to primiparous women. Finally, proband mothers were included only if they could be linked to their parents. The disability to identify many of the grandparents makes our groupings of second- and third-degree relatives incomplete. Despite our large sample size, at that place were not enough pairs of sisters or mothers and daughters that both experienced incident psychiatric disorders in the postpartum period following the birth of their first child to address recurrence chance of only postpartum psychiatric disorders. Our sample size besides limited our ability to examine specific types of psychiatric disorders in the postpartum menstruation every bit nosotros did for the relatives. We also did not see an expected pattern of familial risk aligned with the coefficient of relationship and were underpowered to evaluate familial risk by blazon of disorder for 3rd-caste relatives, both likely due to incomplete identification of third-degree relatives.

Predicting who volition experience a postpartum psychiatric disorder is a challenge only likewise of groovy importance. The results of this study provide compelling testify that assessment of risk for postpartum psychiatric disease, with a particular focus on history of bipolar disorder, should include inquiring nearly family history of psychiatric disorders in any male or female beginning-degree relative. Thus, inquiring about family unit history in fathers and brothers is as important as obtaining a history of postpartum psychiatric disorders in mothers or sisters. Further, as expected, we found personal psychiatric history to be a stronger independent predictor of postpartum psychiatric disorders than family history. Nonetheless, we constitute associations of family history of psychiatric disorders to be stronger amidst women without a personal psychiatric history, indicating that family history may be especially helpful in a risk-cess tool for new-onset postpartum psychiatric episodes amidst women with no records of psychiatric disorders. Previously, a woman who has a blood brother with bipolar disorder only no personal history of mental illness would not necessarily be identified at higher risk for experiencing a postpartum psychiatric disorder. However, this research provides show that such characteristics may place novel adventure groups for which clinicians could direct additional screening efforts, earlier teaching about symptoms, or earlier referral to mental health resources. Few clinical exercise guidelines include family unit history, just those that do suggest planning the timing of pregnancies in periods of stable mood (44) and increasing surveillance for symptoms of postpartum psychosis in the first two weeks later on childbirth (45), which should also be considered for these novel risk groups.

Clinical do guidelines in the U.s.a. have recently been updated to reflect a growing emphasis on the importance of perinatal mental health screening, but the current guidelines put forth past the Usa Preventive Services Task Force (46) and the American College of Obstetricians and Gynecologists (33) practice not include family history as a consideration for postpartum psychiatric disorders. This is in contrast to other women'south health conditions, such equally breast cancer, in which family history of breast cancer in a commencement-degree relative is described extensively as an important screening consideration despite the magnitude of familial risk being similar to that of postpartum psychiatric disorders (47). Therefore, obtaining family unit history of psychiatric disorders is highly valuable information that should be acknowledged as an of import factor in identifying at-risk women and operationalized in clinical exercise to ameliorate prediction of hazard for postpartum psychiatric illness.

Supplementary Material

supplement

Acknowledgments

Disclosures

This study was funded by the National Constitute of Mental Health (1R01MH104468) to S.M.-B., principal investigator, and co-investigators (T.M.-O., W.C.Chiliad., P.Due south., M.L.Grand., and X.50.). T.Thousand.-O. is supported past iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (LuF Grant R155-2014-1724). N.R.W. acknowledges funding from the Australian National Health and Medical Research Council 1078901, 1087889

S.M.-B. receives inquiry grant back up from Sage Therapeutics and Janssen.

T.Grand.-O., M.L.G., and 10.50 have total access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data assay.

References

1. Munk-Olsen T, Maegbaek ML, Johannsen BM, Liu X, Howard LM, di Florio A, et al. Perinatal psychiatric episodes: a population-based study on handling incidence and prevalence. Translational Psychiatry. Nature Publishing Group. 2016;6(10):e919. [PMC complimentary commodity] [PubMed] [Google Scholar]

two. Munk-Olsen T, Laursen TM, Pedersen CB, Mors O, Mortensen PB. New Parents and Mental Disorders. Jama. 2006;296(21):2582–nine. [PubMed] [Google Scholar]

iii. Meltzer-Brody S, Maegbaek ML, Medland SE, Miller WC, Sullivan P, Munk-Olsen T. Obstetrical, pregnancy and socio-economic predictors for new-onset severe postpartum psychiatric disorders in primiparous women. Psychological Medicine. 2017:1–15. [PMC complimentary article] [PubMed] [Google Scholar]

4. O'Hara MW, Wisner KL. Best Practise and Inquiry: Clinical Obstetrics and Gynaecology. 1. Vol. 28. Elsevier Ltd; 2014. Perinatal mental illness: Definition, clarification and aetiology; pp. 3–12. [PMC gratuitous article] [PubMed] [Google Scholar]

v. Howard LM, Molyneaux Due east, Dennis CL, Rochat T, Stein A, Milgrom J. The Lancet. 9956. Vol. 384. Elsevier Ltd; 2014. Non-psychotic mental disorders in the perinatal period; pp. 1775–88. [PubMed] [Google Scholar]

half-dozen. Di Florio A, Forty L, Gordon-Smith K, Heron J, Jones L, Craddock Due north, et al. Perinatal episodes across the mood disorder spectrum. JAMA psychiatry. 2013;70(2):168–75. [PubMed] [Google Scholar]

seven. Viguera Ac, Tondo L, Koukopoulos AE, Reginaldi D, Lepri B, Baldessarini RJ. Episodes of Mood Disorders in ii,252 Pregnancies and Postpartum Periods. Am J Psychiatry. 2011;168:1179–86. [PubMed] [Google Scholar]

8. Rasmussen M-LH, Strøm M, Wohlfahrt J, Videbech P, Melbye M. Risk, handling duration, and recurrence run a risk of postpartum affective disorder in women with no prior psychiatric history: A population-based accomplice study. PLoS ONE. 2017;14(9):e1002392. [PMC free commodity] [PubMed] [Google Scholar]

9. Craddock N, Forty L. Genetics of affective (mood) disorders. European periodical of human genetics : EJHG. 2006;fourteen(6):660–8. [PubMed] [Google Scholar]

x. Lichtenstein P, Yip BH, Björk C, Pawitan Y, Cannon TD, Sullivan PF, et al. Common genetic influences for schizophrenia and bipolar disorder: A population-based study of 2 one thousand thousand nuclear families. Lancet. 2009;373(9659):234–9. [PMC gratuitous commodity] [PubMed] [Google Scholar]

xi. Viktorin A, Meltzer-Brody S, Kuja-Halkola R, Sullivan PF, Landén Thou, Lichtenstein P, et al. Heritability of perinatal low and genetic overlap with nonperinatal low. American Journal of Psychiatry. 2016;173(two):158–65. [PubMed] [Google Scholar]

12. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression : Review and meta-assay. American Journal of Psychiatry. 2000;157(10):1552–62. [PubMed] [Google Scholar]

13. Wray NR, Gottesman II. Using summary data from the Danish National Registers to gauge heritabilities for schizophrenia, bipolar disorder, and major depressive disorder. Frontiers in Genetics. 2012 Jul;iii:1–12. [PMC gratuitous article] [PubMed] [Google Scholar]

14. Jones I, Craddock Northward. Familiality of the puerperal trigger in bipolar disorder: results of a family study. The American Journal of Psychiatry. 2001;158(half-dozen):253–64. [PubMed] [Google Scholar]

15. Murphy-Eberenz G, Zandi PP, March D, Crowe RR, Scheftner WA, Alexander Thousand, et al. Is perinatal low familial? Journal of Affective Disorders. 2006;90(1):49–55. [PubMed] [Google Scholar]

16. Payne JL, Mackinnon DF, Mondimore FM, Mcinnis MG, Schweizer B, Zamoiski RB, et al. Familial assemblage of postpartum mood symptoms in bipolar disorder pedigrees. Bipolar Disorders. 2008;10(1):38–44. [PMC free article] [PubMed] [Google Scholar]

17. Jones I, Craddock N. Do puerperal psychotic episodes identify a more than familial subtype of bipolar disorder? Results of a family history written report. Psychiatric genetics. 2002;12(3):177–80. [PubMed] [Google Scholar]

18. Munk-olsen T, Laursen TM, Meltzer-Brody S, Mortensen Lead, Jones I. Psychiatric Disorders With Postpartum Onset. Archives of general psychiatry. 2012;69(4):428–34. [PubMed] [Google Scholar]

19. Chaudron LH, Pies RW. The Relationship betwixt Postpartum Psychosis and Bipolar Disorder: A Review. Journal of Clinical Psychiatry. 2003;64(11):1284–92. [PubMed] [Google Scholar]

twenty. Dennis C-L, Ross LE. The clinical utility of maternal self-reported personal and familial psychiatric history in identifying women at risk for postpartum low. Acta Obstetrica et Gynecologica. 2006;85:1179–85. [PubMed] [Google Scholar]

21. Forty Fifty, Jones L, Macgregor S, Caesar Southward, Cooper C, Hough A, et al. Familiality of postpartum depression in unipolar disorder: Results of a family unit study. American Periodical of Psychiatry. 2006;163(ix):1549–53. [PubMed] [Google Scholar]

22. Treloar SA, Martin NG, Bucholz KK, Madden PA, Heath AC. Genetic influences on postnatal depressive symptoms: findings from an Australian twin sample. Psychological medicine. 1999 May;29(3):645–54. [PubMed] [Google Scholar]

24. Molina KM, Molina KM, Goltz HH, Kowalkouski MA, Hart SL, Latini D, et al. Recurrence Risk Ratio Encyclopedia of Behavioral Medicine. New York, NY: Springer New York; 2013. pp. 1633–1633. [Google Scholar]

25. Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2003;123C(i):48–58. [PubMed] [Google Scholar]

26. Lichtenstein P, Björk C, Hultman CM, Scolnick E, Sklar P, Sullivan PF. Recurrence risks for schizophrenia in a Swedish national cohort. Psychological medicine. 2006;36(10):1417–25. [PubMed] [Google Scholar]

27. Pedersen CB. The Danish Ceremonious Registration System. Scandinavian Journal of Public Health. 2011;39(Suppl 7):22–5. [PubMed] [Google Scholar]

28. Mors O, Perto GP, Mortensen Atomic number 82. The Danish Psychiatric Fundamental Research Register. Scandinavian Journal of Public Health. 2011;39(Suppl seven):54–7. [PubMed] [Google Scholar]

29. Kessing L. Validity of diagnoses and other clinical register data in patients with affective disorder. European Psychiatry. 1998;13(8):392–eight. [PubMed] [Google Scholar]

30. Gavin NI, Gaynes BN, Lohr KN, Meltzer-brody Due south, Gartlehner G, Swinson T. Perinatal Depression: A Systematic Review of Prevalence and Incidence. Obstetrics and Gynecology. 2005;106(5):1071–83. [PubMed] [Google Scholar]

31. Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. The British journal of psychiatry : the journal of mental science. 1987 May;150:662–73. [PubMed] [Google Scholar]

32. Munk-Olsen T, Laursen TM, Mendelson T, Pedersen CB, Mors O, Mortensen Pb. Risks and predictors of readmission for a mental disorder during the postpartum menses. Archives of full general psychiatry. 2009;66(2):189–95. [PubMed] [Google Scholar]

33. American Higher of Obstetricians and Gynecologists. Screening for Perinatal Depression. 2015:ane–four. [Google Scholar]

34. Stuart-Parrigon Thousand, Stuart Southward. Perinatal Low: An Update and Overview. Current Psychiatry Reports. 2014;16(9) [PMC costless commodity] [PubMed] [Google Scholar]

35. Duncan LE, Ratanatharathorn A, Aiello AE, Almli LM, Amstadter AB, Ashley-Koch AE, et al. Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability Molecular psychiatry. Nature Publishing Group; 2017. Feb, pp. 1–eight. [PMC free article] [PubMed] [Google Scholar]

36. Currier D, Mann MJ, Oquendo MA, Galfalvy H, Isle of mann JJ. Sex differences in the familial transmission of mood disorders. Journal of Affective Disorders. 2006;95(1–3):51–threescore. [PubMed] [Google Scholar]

37. Jansson Chiliad, Gatz Chiliad, Berg S, Johansson B, Malmberg B, McClearn GE, et al. Gender differences in heritability of depressive symptoms in the elderly. Psychological Medicine. 2004;34:471–9. [PubMed] [Google Scholar]

38. Fernandez-Pujals AM, Adams MJ, Thomson P, McKechanie AG, Blackwood DHR, Smith BH, et al. Epidemiology and heritability of major depressive disorder, stratified by age of onset, sex, and illness course in generation Scotland: Scottish family wellness study (GS: SFHS) PLoS I. 2015;10(xi):ane–xviii. [PMC complimentary article] [PubMed] [Google Scholar]

39. Jones I, Chandra PS, Dazzan P, Howard LM. The Lancet. 9956. Vol. 384. Elsevier Ltd; 2014. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period; pp. 1789–99. [PubMed] [Google Scholar]

xl. Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJM, Kushner SA, Bergink V. Risk of postpartum relapse in bipolar disorder and postpartum psychosis: A systematic review and meta-analysis. American Journal of Psychiatry. 2016;173(ii):117–27. [PubMed] [Google Scholar]

41. Reich T, Winokur Thousand. Postpartum psychoses in patients with manic depressive illness. J Nerv Ment Dis. 1970:60–eight. [PubMed] [Google Scholar]

42. Dean C, Williams RJ, Brockington IF. Is puerperal psychosis the same as bipolar manic-depressive disorder? A family study. Psychol Med. 1989:637–47. [PubMed] [Google Scholar]

43. Postpartum Depression: Action Towards Causes and Handling (PACT) Consortium. Heterogeneity of postpartum low: a latent class assay. The Lancet Psychiatry. 2015;2(one):59–67. [PMC free commodity] [PubMed] [Google Scholar]

44. BC Reproductive Mental Program Wellness & Services Perinatal BC. Best Practice Guidelines for Mental Health Disorders in the Perinatal Period. 2014 [Google Scholar]

45. Howard LM, Megnin-Viggars O, Symington I, Pilling S. Antenatal and postnatal mental health: summary of updated Dainty guidance. Bmj. 2014;349:g7394–g7394. [PubMed] [Google Scholar]

46. Siu AL, U.s. Preventive Services Task Force Screening for Depression in Adults: United states Preventive Services Task Strength Recommendation Argument. JAMA. 2016;315(4):380–7. [PubMed] [Google Scholar]

47. Siu AL, US Preventive Services Task Force Screening for Breast Cancer: U.Due south. Preventive Services Job Forcefulness Recommendation Statement. Annals of Internal Medicine. 2016;164(4):279–97. [PubMed] [Google Scholar]

fischerhoucter.blogspot.com

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070397/