[Skip to Content]
[Skip to Content Landing]
Figure 1.  Flowchart of the Study Selection Process
Flowchart of the Study Selection Process
Figure 2.  Forest Plot of Summary Odds Ratio
Forest Plot of Summary Odds Ratio

Individual curves reflect the posterior distribution for each of the included studies and the summary effect in the meta-analysis. The dotted black line at x = 1 provides the overall cut point for inference. The dashed and dotted lines provide the point estimate and 95% credible intervals for the summary effect.

Figure 3.  Posterior Distribution for the Summary Odds Ratio
Posterior Distribution for the Summary Odds Ratio

The posterior distribution for the summary odds ratio is provided, along with the point estimate (dotted blue line at the median) and 95% credible intervals (dotted blue lines on either side of the median) to describe uncertainty. The dotted black line at x = 1 provides the overall cut point for inference. The shaded portion of the distribution corresponds with the posterior probability that the odds ratio is greater than 1 of 98.6%.

Table 1.  Characteristics of Included Studies
Characteristics of Included Studies
Table 2.  Influence Analysis Results
Influence Analysis Results
1.
Gaynes  BN, Gavin  N, Meltzer-Brody  S,  et al.  Perinatal depression: prevalence, screening accuracy, and screening outcomes.   Evid Rep Technol Assess (Summ). 2005;(119):1-8. doi:10.1037/e439372005-001PubMedGoogle Scholar
2.
Bennett  HA, Einarson  A, Taddio  A, Koren  G, Einarson  TR.  Prevalence of depression during pregnancy: systematic review.   Obstet Gynecol. 2004;103(4):698-709. doi:10.1097/01.AOG.0000116689.75396.5fPubMedGoogle ScholarCrossref
3.
Ko  JY, Rockhill  KM, Tong  VT, Morrow  B, Farr  SL.  Trends in postpartum depressive symptoms—27 states, 2004, 2008, and 2012.   MMWR Morb Mortal Wkly Rep. 2017;66(6):153-158. doi:10.15585/mmwr.mm6606a1PubMedGoogle ScholarCrossref
4.
Slomian  J, Honvo  G, Emonts  P, Reginster  J-Y, Bruyère  O.  Consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes.   Womens Health (Lond). 2019;15:1745506519844044. doi:10.1177/1745506519844044PubMedGoogle Scholar
5.
Mikšić  Š, Miškulin  M, Juranić  B, Rakošec  Ž, Včev  A, Degmečić  D.  Depression and suicidality during pregnancy.   Psychiatr Danub. 2018;30(1):85-90. doi:10.24869/psyd.2018.85PubMedGoogle ScholarCrossref
6.
Murray  L, Cooper  P, Fearon  P.  Parenting difficulties and postnatal depression: implications for primary healthcare assessment and intervention.   Community Pract. 2014;87(11):34-38.PubMedGoogle Scholar
7.
Fihrer  I, McMahon  CA, Taylor  AJ.  The impact of postnatal and concurrent maternal depression on child behaviour during the early school years.   J Affect Disord. 2009;119(1-3):116-123. doi:10.1016/j.jad.2009.03.001PubMedGoogle ScholarCrossref
8.
Thompson  SM, Jiang  L, Hammen  C, Whaley  SE.  Association of maternal depressive symptoms and offspring physical health in low-income families.   Matern Child Health J. 2018;22(6):874-882. doi:10.1007/s10995-018-2462-9PubMedGoogle ScholarCrossref
9.
Grace  SL, Evindar  A, Stewart  DE.  The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature.   Arch Womens Ment Health. 2003;6(4):263-274. doi:10.1007/s00737-003-0024-6PubMedGoogle ScholarCrossref
10.
Goodman  JH.  Paternal postpartum depression, its relationship to maternal postpartum depression, and implications for family health.   J Adv Nurs. 2004;45(1):26-35. doi:10.1046/j.1365-2648.2003.02857.xPubMedGoogle ScholarCrossref
11.
Betts  KS, Williams  GM, Najman  JM, Alati  R.  Maternal depressive, anxious, and stress symptoms during pregnancy predict internalizing problems in adolescence.   Depress Anxiety. 2014;31(1):9-18. doi:10.1002/da.22210PubMedGoogle ScholarCrossref
12.
Van Batenburg-Eddes  T, Brion  MJ, Henrichs  J,  et al.  Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study.   J Child Psychol Psychiatry. 2013;54(5):591-600. doi:10.1111/jcpp.12023PubMedGoogle ScholarCrossref
13.
Azeredo  CM, Santos  IS, Barros  AJD, Barros  FC, Matijasevich  A.  Maternal depression and bullying victimization among adolescents: results from the 2004 Pelotas cohort study.   Depress Anxiety. 2017;34(10):897-907. doi:10.1002/da.22662PubMedGoogle ScholarCrossref
14.
Capron  LE, Glover  V, Pearson  RM,  et al.  Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.   J Affect Disord. 2015;187:20-26. doi:10.1016/j.jad.2015.08.012PubMedGoogle ScholarCrossref
15.
Leis  JA, Heron  J, Stuart  EA, Mendelson  T.  Associations between maternal mental health and child emotional and behavioral problems: does antenatal mental health matter?   J Abnorm Child Psychol. 2014;42(1):161-171. doi:10.1007/s10802-013-9766-4PubMedGoogle ScholarCrossref
16.
Stein  A, Gath  DH, Bucher  J, Bond  A, Day  A, Cooper  PJ.  The relationship between postnatal depression and mother-child interaction.   Br J Psychiatry. 1991;158:46-52. doi:10.1192/bjp.158.1.46PubMedGoogle ScholarCrossref
17.
Kingston  D, Tough  S, Whitfield  H.  Antenatal and postpartum maternal psychological distress and infant development: a systematic review.   Child Psychiatry Hum Dev. 2012;43(5):683-714. doi:10.1007/s10578-012-0291-4PubMedGoogle ScholarCrossref
18.
Sullivan  PF, Neale  MC, Kendler  KS.  Genetic epidemiology of major depression: review and meta-analysis.   Am J Psychiatry. 2000;157(10):1552-1562. doi:10.1176/appi.ajp.157.10.1552PubMedGoogle ScholarCrossref
19.
Caspi  A, Moffitt  TE.  Gene-environment interactions in psychiatry: joining forces with neuroscience.   Nat Rev Neurosci. 2006;7(7):583-590. doi:10.1038/nrn1925PubMedGoogle ScholarCrossref
20.
Polderman  TJC, Benyamin  B, de Leeuw  CA,  et al.  Meta-analysis of the heritability of human traits based on fifty years of twin studies.   Nat Genet. 2015;47(7):702-709. doi:10.1038/ng.3285PubMedGoogle ScholarCrossref
21.
McAdams  TA, Rijsdijk  FV, Neiderhiser  JM,  et al.  The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.   Psychol Med. 2015;45(12):2583-2594. doi:10.1017/S0033291715000501PubMedGoogle ScholarCrossref
22.
Hannigan  LJ, Eilertsen  EM, Gjerde  LC,  et al.  Maternal antenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study.   Lancet Psychiatry. 2018;5(10):808-815. doi:10.1016/S2215-0366(18)30225-6PubMedGoogle ScholarCrossref
23.
Dagher  RK, Hofferth  SL, Lee  Y.  Maternal depression, pregnancy intention, and return to paid work after childbirth.   Womens Health Issues. 2014;24(3):e297-e303. doi:10.1016/j.whi.2014.03.002PubMedGoogle ScholarCrossref
24.
Kohlhoff  J, Barnett  B.  Parenting self-efficacy: links with maternal depression, infant behaviour, and adult attachment.   Early Hum Dev. 2013;89(4):249-256. doi:10.1016/j.earlhumdev.2013.01.008PubMedGoogle ScholarCrossref
25.
Prenoveau  J, Craske  M, Counsell  N,  et al.  Postpartum GAD is a risk factor for postpartum MDD: the course and longitudinal relationships of postpartum GAD and MDD.   Depress Anxiety. 2013;30(6):506-514. doi:10.1002/da.22040PubMedGoogle ScholarCrossref
26.
Beeber  LS, Schwartz  TA, Martinez  MI,  et al.  Depressive symptoms and compromised parenting in low-income mothers of infants and toddlers: distal and proximal risks.   Res Nurs Health. 2014;37(4):276-291. doi:10.1002/nur.21604PubMedGoogle ScholarCrossref
27.
O’Connor  TG, Tang  W, Gilchrist  MA, Moynihan  JA, Pressman  EK, Blackmore  ER.  Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study.   Biol Psychol. 2014;96:35-41. doi:10.1016/j.biopsycho.2013.11.002PubMedGoogle ScholarCrossref
28.
Glynn  LM, Howland  MA, Sandman  CA,  et al.  Antenatal maternal mood patterns predict child temperament and adolescent mental health.   J Affect Disord. 2018;228:83-90. doi:10.1016/j.jad.2017.11.065PubMedGoogle ScholarCrossref
29.
Rifkin-Graboi  A, Bai  J, Chen  H,  et al.  Antenatal maternal depression associates with microstructure of right amygdala in neonates at birth.   Biol Psychiatry. 2013;74(11):837-844. doi:10.1016/j.biopsych.2013.06.019PubMedGoogle ScholarCrossref
30.
Qiu  A, Shen  M, Buss  C,  et al; the GUSTO study group.  Effects of antenatal maternal depressive symptoms and socioeconomic status on neonatal brain development are modulated by genetic risk.   Cereb Cortex. 2017;27(5):3080-3092. doi:10.1093/cercor/bhx065PubMedGoogle ScholarCrossref
31.
Milgrom  J, Gemmill  AW, Bilszta  JL,  et al.  Antenatal risk factors for postnatal depression: a large prospective study.   J Affect Disord. 2008;108(1-2):147-157. doi:10.1016/j.jad.2007.10.014PubMedGoogle ScholarCrossref
32.
Robertson  E, Grace  S, Wallington  T, Stewart  DE.  Antenatal risk factors for postpartum depression: a synthesis of recent literature.   Gen Hosp Psychiatry. 2004;26(4):289-295. doi:10.1016/j.genhosppsych.2004.02.006PubMedGoogle ScholarCrossref
33.
McEwen  BS.  Effects of stress on the developing brain.   Cerebrum. 2011;2011:14.PubMedGoogle Scholar
34.
Azar  R, Mercer  D.  Mild depressive symptoms are associated with elevated C-reactive protein and proinflammatory cytokine levels during early to midgestation: a prospective pilot study.   J Womens Health (Larchmt). 2013;22(4):385-389. doi:10.1089/jwh.2012.3785PubMedGoogle ScholarCrossref
35.
Achtyes  E, Keaton  SA, Smart  L,  et al.  Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression.   Brain Behav Immun. 2020;83:239-247. doi:10.1016/j.bbi.2019.10.017PubMedGoogle ScholarCrossref
36.
Osborne  S, Biaggi  A, Chua  TE,  et al.  Antenatal depression programs cortisol stress reactivity in offspring through increased maternal inflammation and cortisol in pregnancy: the Psychiatry Research and Motherhood–Depression (PRAM-D) Study.   Psychoneuroendocrinology. 2018;98:211-221. doi:10.1016/j.psyneuen.2018.06.017PubMedGoogle ScholarCrossref
37.
Pearson  RM, Evans  J, Kounali  D,  et al.  Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.   JAMA Psychiatry. 2013;70(12):1312-1319. doi:10.1001/jamapsychiatry.2013.2163PubMedGoogle ScholarCrossref
38.
Pawlby  S, Hay  DF, Sharp  D, Waters  CS, O’Keane  V.  Antenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based study.   J Affect Disord. 2009;113(3):236-243. doi:10.1016/j.jad.2008.05.018PubMedGoogle ScholarCrossref
39.
Murray  L, Arteche  A, Fearon  P, Halligan  S, Goodyer  I, Cooper  P.  Maternal postnatal depression and the development of depression in offspring up to 16 years of age.   J Am Acad Child Adolesc Psychiatry. 2011;50(5):460-470. doi:10.1016/j.jaac.2011.02.001PubMedGoogle ScholarCrossref
40.
Netsi  E, Pearson  RM, Murray  L, Cooper  P, Craske  MG, Stein  A.  Association of persistent and severe postnatal depression with child outcomes.   JAMA Psychiatry. 2018;75(3):247-253. doi:10.1001/jamapsychiatry.2017.4363PubMedGoogle ScholarCrossref
41.
Hay  DF, Pawlby  S, Waters  CS, Sharp  D.  Antepartum and postpartum exposure to maternal depression: different effects on different adolescent outcomes.   J Child Psychol Psychiatry. 2008;49(10):1079-1088. doi:10.1111/j.1469-7610.2008.01959.xPubMedGoogle ScholarCrossref
42.
Quarini  C, Pearson  RM, Stein  A, Ramchandani  PG, Lewis  G, Evans  J.  Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?   J Affect Disord. 2016;189:329-335. doi:10.1016/j.jad.2015.09.039PubMedGoogle ScholarCrossref
43.
Plant  DT, Pariante  CM, Sharp  D, Pawlby  S.  Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment.   Br J Psychiatry. 2015;207(3):213-220. doi:10.1192/bjp.bp.114.156620PubMedGoogle Scholar
44.
Hammerton  G, Mahedy  L, Mars  B,  et al.  Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation.   PLoS One. 2015;10(7):e0131885. doi:10.1371/journal.pone.0131885PubMedGoogle Scholar
45.
Hammen  C, Brennan  PA.  Severity, chronicity, and timing of maternal depression and risk for adolescent offspring diagnoses in a community sample.   Arch Gen Psychiatry. 2003;60(3):253-258. doi:10.1001/archpsyc.60.3.253PubMedGoogle Scholar
46.
Tomlinson  M, Rotheram-Borus  MJ, Scheffler  A, le Roux  I.  Antenatal depressed mood and child cognitive and physical growth at 18-months in South Africa: a cluster randomised controlled trial of home visiting by community health workers.   Epidemiol Psychiatr Sci. 2018;27(6):601-610. doi:10.1017/S2045796017000257PubMedGoogle Scholar
47.
Verkuijl  NE, Richter  L, Norris  SA, Stein  A, Avan  B, Ramchandani  PG.  Postnatal depressive symptoms and child psychological development at 10 years: a prospective study of longitudinal data from the South African Birth to Twenty cohort.   Lancet Psychiatry. 2014;1(6):454-460. doi:10.1016/S2215-0366(14)70361-XPubMedGoogle Scholar
48.
Pietikäinen  JT, Kiviruusu  O, Kylliäinen  A,  et al.  Maternal and paternal depressive symptoms and children’s emotional problems at the age of 2 and 5 years: a longitudinal study.   J Child Psychol Psychiatry. 2020;61(2):195-204. doi:10.1111/jcpp.13126PubMedGoogle Scholar
49.
Ouzzani  M, Hammady  H, Fedorowicz  Z, Elmagarmid  A.  Rayyan—a web and mobile app for systematic reviews.   Syst Rev. 2016;5(1):210. doi:10.1186/s13643-016-0384-4PubMedGoogle Scholar
50.
Jaworska  N, MacQueen  G.  Adolescence as a unique developmental period.   J Psychiatry Neurosci. 2015;40(5):291-293. Published correction appears in  J Psychiatry Neurosci. 2015;40(6):386. doi:10.1503/jpn.150268PubMedGoogle Scholar
51.
Viechtbauer  W.  Conducting meta-analyses in R with the metafor package.   J Stat Softw. 2010;36(1):1-48. doi:10.18637/jss.v036.i03PubMedGoogle Scholar
52.
Bürkner  P-C.  Advanced Bayesian multilevel modeling with the R package brms.   R Journal. 2018;10(1):395-411. doi:10.32614/RJ-2018-017Google Scholar
53.
R Core Team.  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2019.
54.
Harrer  M, Cuijpers  P, Furukawa  TA, Ebert  DD.  Doing meta-analysis in R: a hands-on guide. Published 2019. Accessed May 12, 2020. doi:10.5281/zenodo.2551803
55.
Williams  DR, Rast  P, Bürkner  P-C.  Bayesian meta-analysis with weakly informative prior distributions.  January 2018. doi:10.31234/https://osf.io/7tbrm
56.
McElreath  R.  Statistical Rethinking: A Bayesian Course with Examples in R and Stan. CRC Press; 2016.
57.
Gelman  A, Jakulin  A, Pittau  MG, Su  Y-S.  A weakly informative default prior distribution for logistic and other regression models.   Ann Appl Stat. 2008;2(4):1360-1383. doi:10.1214/08-AOAS191Google Scholar
58.
Bürkner  P-C, Williams  DR, Simmons  TC, Woolley  JD.  Intranasal oxytocin may improve high-level social cognition in schizophrenia, but not social cognition or neurocognition in general: a multilevel Bayesian meta-analysis.   Schizophr Bull. 2017;43(6):1291-1303. doi:10.1093/schbul/sbx053PubMedGoogle Scholar
59.
Chang  BH, Hoaglin  DC.  Meta-analysis of odds ratios: current good practices.   Med Care. 2017;55(4):328-335. doi:10.1097/MLR.0000000000000696PubMedGoogle Scholar
60.
Glasheen  C, Richardson  GA, Kim  KH, Larkby  CA, Swartz  HA, Day  NL.  Exposure to maternal pre- and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring.   Dev Psychopathol. 2013;25(4 Pt 1):1045-1063. doi:10.1017/S0954579413000369PubMedGoogle Scholar
61.
Raposa  E, Hammen  C, Brennan  P, Najman  J.  The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.   J Adolesc Health. 2014;54(1):88-93. doi:10.1016/j.jadohealth.2013.07.038PubMedGoogle Scholar
62.
Taka-Eilola Nèe Riekki  T, Veijola  J, Murray  GK, Koskela  J, Mäki  P.  Severe mood disorders and schizophrenia in the adult offspring of antenatally depressed mothers in the Northern Finland 1966 Birth Cohort: relationship to parental severe mental disorder.   J Affect Disord. 2019;249:63-72. doi:10.1016/j.jad.2019.02.011PubMedGoogle Scholar
63.
Stroup  DF, Berlin  JA, Morton  SC,  et al; Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group.  Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting.   JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008PubMedGoogle Scholar
64.
Wells  GA, Shea  B, O’Connell  D,  et al.  The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses.  Published 2012. Accessed May 12, 2020. http://wwwohrica/programs/clinical_epidemiology/oxford.asp
65.
Pierce  M, Hope  HF, Kolade  A,  et al  Effects of parental mental illness on children's physical health: systematic review and meta-analysis.   Br J Psychiatry. 2019;Oct 15:1-10. doi:10.1192/bjp.2019.216Google Scholar
66.
Dietz  LJ, Birmaher  B, Williamson  DE,  et al.  Mother-child interactions in depressed children and children at high risk and low risk for future depression.   J Am Acad Child Adolesc Psychiatry. 2008;47(5):574-582. doi:10.1097/CHI.0b013e3181676595PubMedGoogle Scholar
67.
Lewinsohn  PM, Rohde  P, Klein  DN, Seeley  JR.  Natural course of adolescent major depressive disorder: I. continuity into young adulthood.   J Am Acad Child Adolesc Psychiatry. 1999;38(1):56-63. doi:10.1097/00004583-199901000-00020PubMedGoogle Scholar
68.
Harrington  R, Fudge  H, Rutter  M, Pickles  A, Hill  J.  Adult outcomes of childhood and adolescent depression. I. Psychiatric status.   Arch Gen Psychiatry. 1990;47(5):465-473. doi:10.1001/archpsyc.1990.01810170065010PubMedGoogle Scholar
69.
Davidovich  S, Collishaw  S, Thapar  AK, Harold  G, Thapar  A, Rice  F.  Do better executive functions buffer the effect of current parental depression on adolescent depressive symptoms?   J Affect Disord. 2016;199:54-64. doi:10.1016/j.jad.2016.03.049PubMedGoogle Scholar
70.
Kember  RL, Dempster  EL, Lee  THA, Schalkwyk  LC, Mill  J, Fernandes  C.  Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse.   Brain Behav. 2012;2(4):455-467. doi:10.1002/brb3.69PubMedGoogle Scholar
71.
Elliott  E, Ezra-Nevo  G, Regev  L, Neufeld-Cohen  A, Chen  A.  Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice.   Nat Neurosci. 2010;13(11):1351-1353. doi:10.1038/nn.2642PubMedGoogle Scholar
72.
Chertkow-Deutsher  Y, Cohen  H, Klein  E, Ben-Shachar  D.  DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2.   Int J Neuropsychopharmacol. 2010;13(3):347-359. doi:10.1017/S146114570999071XPubMedGoogle Scholar
73.
Franklin  TB, Russig  H, Weiss  IC,  et al.  Epigenetic transmission of the impact of early stress across generations.   Biol Psychiatry. 2010;68(5):408-415. doi:10.1016/j.biopsych.2010.05.036PubMedGoogle Scholar
74.
Peña  CJ, Neugut  YD, Champagne  FA.  Developmental timing of the effects of maternal care on gene expression and epigenetic regulation of hormone receptor levels in female rats.   Endocrinology. 2013;154(11):4340-4351. doi:10.1210/en.2013-1595PubMedGoogle Scholar
75.
Angold  A, Costello  EJ, Erkanli  A, Worthman  CM.  Pubertal changes in hormone levels and depression in girls.   Psychol Med. 1999;29(5):1043-1053. doi:10.1017/S0033291799008946PubMedGoogle Scholar
76.
Silberg  J, Pickles  A, Rutter  M,  et al.  The influence of genetic factors and life stress on depression among adolescent girls.   Arch Gen Psychiatry. 1999;56(3):225-232. doi:10.1001/archpsyc.56.3.225PubMedGoogle Scholar
77.
Carlson  GA.  The challenge of diagnosing depression in childhood and adolescence.   J Affect Disord. 2000;61(suppl 1):3-8. doi:10.1016/S0165-0327(00)00283-4PubMedGoogle Scholar
78.
Tackett  JL, Lahey  BB, van Hulle  C, Waldman  I, Krueger  RF, Rathouz  PJ.  Common genetic influences on negative emotionality and a general psychopathology factor in childhood and adolescence.   J Abnorm Psychol. 2013;122(4):1142-1153. doi:10.1037/a0034151PubMedGoogle Scholar
79.
Caspi  A, Houts  RM, Belsky  DW,  et al.  The p factor: one general psychopathology factor in the structure of psychiatric disorders?   Clin Psychol Sci. 2014;2(2):119-137. doi:10.1177/2167702613497473PubMedGoogle Scholar
80.
Cox  EQ, Sowa  NA, Meltzer-Brody  SE, Gaynes  BN.  The perinatal depression treatment cascade: baby steps toward improving outcomes.   J Clin Psychiatry. 2016;77(9):1189-1200. doi:10.4088/JCP.15r10174PubMedGoogle Scholar
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Views 2,770
    Citations 0
    Original Investigation
    Psychiatry
    June 30, 2020

    Risk of Depression in the Adolescent and Adult Offspring of Mothers With Perinatal Depression: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston
    • 2Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
    • 3Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern School of Medicine, University of Texas Health Science Center at Houston
    • 4Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, University of Texas Health Science Center at Houston
    • 5Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands
    • 6Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
    • 7Department of Internal Medicine, Mercy Health St Vincent Medical Center, Toledo, Ohio
    • 8Center for Clinical Research and Evidence-Based Medicine, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston
    • 9Medical Sciences Division, Department of Psychiatry, University of Oxford, Oxford, United Kingdom
    JAMA Netw Open. 2020;3(6):e208783. doi:10.1001/jamanetworkopen.2020.8783
    Key Points español 中文 (chinese)

    Question  Is maternal perinatal depression associated with increased risk of offspring depression in adolescence and adulthood?

    Findings  In this systematic review and meta-analysis that examined 6 prospective longitudinal studies involving 15 584 mother-child dyads, a 70% increase in the odds of adolescent and adult offspring depression was noted among offspring of mothers who had perinatal depression.

    Meaning  In this study, maternal perinatal depression was associated with the risk of depression in adolescence and adulthood among offspring; future studies aimed at exploring the neurobiological mechanism of risk transmission and postinterventional risk reduction could improve the management of depressive disorders.

    Abstract

    Importance  Maternal depression during pregnancy is associated with emotional and behavioral difficulties of offspring during childhood that can increase the risk of depression in adolescence and adulthood.

    Objective  To investigate the association between perinatal maternal depression and an increased long-term risk of depression in their adolescent and adult offspring.

    Data Sources  A systematic search of the electronic databases of PubMed and PsycINFO was conducted from May 2019 to June 2019.

    Study Selection  A total of 6309 articles were identified, of which 88 articles were extracted for full-text review by 2 reviewers. Only articles reporting data from prospective longitudinal studies that assessed maternal depression during antenatal and/or postnatal periods and resulting offspring 12 years or older with measures of established psychometric properties were included. Exclusion criteria consisted of all other study designs, mothers with other medical and psychiatric comorbidities, and offspring younger than 12 years.

    Data Extraction and Synthesis  Data were extracted by 2 independent reviewers, and discrepancies were mediated by an expert third reviewer. Meta-analysis was performed using Bayesian statistical inference and reported using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline. The association of depression timing with the sex of offspring was explored using metaregression.

    Main Outcomes and Measures  Offspring depression was evaluated using standardized depression scales or clinical interviews.

    Results  Six studies with a total of 15 584 mother-child dyads were included in the meta-analysis, which found the offspring of mothers who experienced perinatal depression to have increased odds of depression (odds ratio [OR], 1.70; 95% credible interval [CrI], 1.60-2.65; posterior probability [PP] [OR >1], 98.6%). Although metaregression found no evidence for an overall association between perinatal depression timing and offspring depression (antenatal vs postnatal, PP [OR >1] = 53.8%), subgroup analyses showed slightly higher pooled odds for the antenatal studies (OR, 1.78; 95% CrI, 0.93-3.33; PP [OR >1] = 96.2%) than for the postnatal studies (OR, 1.66; 95% CrI, 0.65-3.84; PP [OR >1] = 88.0%). Female adolescent offspring recorded higher rates of depression in metaregression analyses, such that a 1% increase in the percentage of female (relative to male) offspring was associated with a 6% increase in the odds of offspring depression (OR, 1.06; 95% CrI, 0.99-1.14; τ2 = 0.31).

    Conclusions and Relevance  In this study, maternal perinatal depression, especially antenatal depression, was associated with the risk of depression in adolescence and adulthood. More research into the mechanisms of depression risk transmission and assessments of postinterventional risk reduction could aid in the development of future strategies to tackle depressive disorders in pregnancy.

    Introduction

    Perinatal depression is a depressive episode that occurs in women during pregnancy (antenatal depression) or within 12 months after pregnancy (postnatal depression). Studies show that approximately 10% to 20% of women experience perinatal depression.1 Antenatal depression is estimated to affect 7.4% to 12.8% of women, with women in their second and third trimesters being most susceptible.2 The prevalence of postnatal depression is estimated to be 10% to 15% of all pregnancies, and it may be as high as 25% in women with low incomes.3 Women with severe maternal depression are at an increased risk of self-harm, suicide, substance use disorder, marital difficulties, and parenting difficulties.4-6 Perinatal depression also affects children by increasing the risk of mental and physical health problems,7,8 thus substantially contributing to family and societal burden. The adverse consequences of perinatal depression on childhood development, including increased behavioral difficulties, impaired cognitive ability, and decreased emotional functioning, have been well established.9-12 Studies have noted that additional consequences in adolescent offspring include anxiety, experiencing bullying, and depression.13-15 Therefore, perinatal depression is a significant health concern as a potentially treatable cause of impaired functioning in offspring.16,17

    Depression is a heterogeneous condition with environmental factors interplaying with genetic susceptibility in the onset of illness.18,19 A 2015 meta-analysis of all twin studies conducted before 2012 reported a modest heritability of 34.4% (95% CI, 30.7%-37.3%) for depressive episodes.20 Perinatal depression in mothers may represent a genetic susceptibility to depression, in addition to having a direct environmental consequences on the offspring. A Children of Twins study (CoTs) analysis that examined the covariation between parental and offspring depression attributed the risk transmission to shared environmental factors rather than shared genes alone.21 Thus, a substantial part of the risk of transmission is likely due to both environmental and genetic factors between mother and offspring.22 Compromised parenting skills, lower socioeconomic conditions, maternal psychiatric comorbidities (particularly postnatal depression), and childhood maltreatment are some of the significant risk factors for offspring depression.23-26 In the case of antenatal depression, the biological stress response has been strongly implicated as a possible mediator of offspring depression.27,28 Some studies have reported significant neurodevelopmental changes in the fetus exposed to antenatal depression, especially in the right amygdala,29,30 hippocampus, and other corticolimbic areas.30 However, the exact mechanism of this risk transmission is still unclear.

    Antenatal depression itself is a risk factor for developing postnatal depression.31,32 Recent studies on early stress and brain development have brought more attention to the biological basis and causal linkage of the occurrence of emotional and behavioral problems in the offspring.33 Elevated levels of peripheral inflammatory markers such as interleukins and C-reactive protein have been reported in both antenatal and postnatal depression.34,35 These peripheral inflammatory biomarkers were also positively correlated with hyperactive cortisol secretion in infants immediately after birth and at age 1 year.36 Therefore, it is critical to comprehensively examine the cumulative and differential associations of perinatal depression timing with outcomes for offspring.

    The estimated risk of adolescent offspring depression associated with perinatal depression varies across different studies and is associated with its timing. Studies37,38 have found that offspring of mothers with antenatal depression were 1.3 to 4.7 times more likely to develop depression. A 4.9- to 7.4-fold increase in the risk of developing depression in adolescence39,40 has been reported in the case of maternal postnatal depression. Although some studies37,38,41 did not report this association, longer follow-up studies using the same cohort data suggest otherwise. Additionally, female offspring of mothers with antenatal depression and male offspring of mothers with postnatal depression are particularly more susceptible to depression according to Quarini et al.42 In the same study, the association by sex was not found in children younger than 12 years, suggesting a likely biopsychological process that took effect only after reaching puberty. While postnatal depression is reported to be associated with depression in offspring of mothers with lower educational attainment,37 antenatal depression is reported to be an overall stronger factor associated with adolescent offspring depression.37,39 Recurrent depressive episodes and the severity of the symptoms in the mother also seem to be associated with the development and prognosis of offspring depression.43-45

    Most studies reporting on the consequences of maternal perinatal depression focus on childhood behavior and development.46-48 To our knowledge, this study is the first of its kind to systematically review the literature and conduct a meta-analysis of all prospective longitudinal cohort studies that examine the association of maternal antenatal and postnatal depression with offspring depression in adolescence and adulthood. The initial hypothesis of this study was that perinatal maternal depression would be associated with an increased long-term risk of depression in adolescent and adult offspring. This study also explored the differences in depression outcomes with respect to the sex of the offspring as well as the timing of the perinatal depression (ie, antenatal vs postnatal depression).

    Methods
    Search Strategy

    A systematic search of the electronic databases of PubMed and PsycINFO was conducted from May 2019 to June 2019. The search criteria included keyword phrases and different variations for postnatal depression OR antenatal depression OR perinatal depression along with terms for adolescent* and adult offspring* (eAppendix in the Supplement). A validated search filter for prospective longitudinal cohort studies built in collaboration with our liaison librarian was used. We then conducted a secondary search on the reference lists of initially identified studies obtained from the primary search to find additional relevant articles.

    The search was limited to studies published in peer-reviewed journals, using human populations. No limitations for language or publication period were set to broaden the scope of the systematic review. Reporting of key characteristics followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.63

    Study Selection and Data Extraction

    This search strategy returned a total of 6923 studies, with 6309 articles remaining after removing duplicates (Figure 1). Only studies examining associations between maternal depression and adolescent and/or adult depression were included. Titles and abstracts retrieved by the systematic search were independently screened by 2 authors (V.T. and R.R.) using Rayyan QCRI49 and filtered according to the inclusion and exclusion criteria. For the purposes of our study, antenatal depression was defined as the presence of depressive symptoms during pregnancy, and postnatal depression was defined as the presence of maternal depressive symptoms within 1 year following delivery.1 We contacted authors for additional information if data was unavailable.

    We had 4 inclusion criteria when determining eligibility for meta-analysis. First, studies included were prospective longitudinal studies following mothers during their pregnancy and/or during the postnatal period and into the offspring’s adolescence and adulthood. Second, mothers should have been screened for depression during pregnancy and/or at least 1 year after pregnancy. Third, the offspring of mothers not exposed to depression during the antenatal and/or postnatal period were to serve as controls for the study group. Offspring aged 12 years or older were defined as adolescents50 and warranted inclusion. Finally, all study outcomes were required to be based on empirical measures with established psychometric properties, such as a standardized depression scale or interview (eg, Edinburgh Postnatal Depression Scale, Standard Psychiatric Interview, Clinical Interview Schedule). Studies that met the following criteria were excluded: cross-sectional studies, retrospective studies, and surveys; mothers with other primary psychiatric or medical comorbidities during pregnancy; and offspring younger than 12 years at the time of assessment for depression. The decision to include or exclude a study was based on a consensus agreement and any discrepancy was mediated by an expert third reviewer (S.S.).

    Articles that fit the search criteria underwent full-text review. Upon further filtering out studies using the same cohort information, 6 articles39,42,43,60-62 were selected for the final review and meta-analysis. The flow of studies through the review selection procedure is shown in Figure 1. The selected studies underwent quality assessment using the Newcastle-Ottawa scale64 (eTable in the Supplement).

    Statistical Analysis

    Meta-analysis was performed using Bayesian statistical inference in the package brms in the R statistical computing environment version 3.6.2 (R Project for Statistical Computing).51-54 Weakly informative priors (Intercept distributed Normal [0,1]; group-level σ distributed half-Cauchy [0,1]) were chosen for the present analysis to minimize the influence on the meta-analytic estimates per recommendations in the literature.55-58 Assumptions of Bayesian modeling were assessed via posterior predictive checking and convergence diagnostics (eg, effective sample size, chain-mixing convergence).

    Effect estimates for the association between maternal and offspring depression were calculated from existing study data using the metafor package in R.51 Effect sizes were weighted by their sample variances. In total, 9 effects were calculated from the 6 peer-reviewed articles included in the meta-analysis. Of these, 3 articles provided results for multiple effects via separate results for both antenatal and postnatal maternal depression, 1 article reported data for antenatal depression only, 1 article reported postnatal depression only, and 1 article reported a combined set of values from antenatal and postnatal mothers. Part of the model-fitting process was to determine the extent to which antenatal and postnatal associations could be modeled jointly, and if so, the degree to which depression timing influenced the summary effects. Given that adjusted effects were only provided in 3 of 6 studies and those that did use adjustment included widely different sets of covariates (and thus were not comparable),59 the present analysis used unadjusted effects from the raw data in each study.

    Pooled log odds and 95% credible intervals (CrIs) were calculated using a multilevel (ie, random-effects) specification, chosen a priori to account for variability across all 9 effects. Log odds were then exponentiated to provide odds ratios (ORs). Given that multiple effects were extracted from 3 of 6 articles, a random intercept for each effect with a hierarchical effect for a paired article identifier was also tested for a superior fit to the data. Goodness-of-fit (leave-one-out cross-validation ) was used to determine the optimal model specification (ie, whether or not the nested intercept improved model fit). A forest plot of Bayesian estimates was generated to visualize the relative contribution of each study to the overall pooled OR as well as the uncertainty within each effect. Metaregression was used to test the potential influence of depression timing and offspring sex (percentage female of offspring sample). Follow-up analyses obtained pooled ORs within each maternal depression timing (antenatal or postnatal). Visual inspection of funnel plot asymmetry and the nonparametric trim-and-fill method were used in the frequentist context (via the metafor package in R) to explore the possibility of publication bias. Individual study influence was investigated via leave-one-out sensitivity analysis, whereby pooled estimates were calculated by omitting each study in turn.

    Results
    Study Characteristics

    Our search strategy yielded 6309 studies, out of which 88 articles underwent full-text review, and 11 original articles meeting the inclusion criteria were identified. Upon further filtering out studies using the same cohort information, 6 articles were selected for the final review and meta-analysis. Key characteristics (ie, title, author information, study design, sample size, location, measuring scales, mean ages of offspring at assessment, and number of male and female participants) of the included articles were reported based on the MOOSE guidelines63 and are shown in Table 1.39,42,43,60-62

    Primary Analysis

    Meta-analysis estimated the pooled OR for the effect of maternal depression on offspring depression including 6 studies (in an overall sample size of 19 535 mother-child dyads). Model specification via leave-one-out cross-validation supported a simple multilevel model above a more complex structure featuring a nested article identifier (ie, only a simple random intercept for each effect was necessary for the present analysis; a nested article identifier for each effect demonstrated worse fit). The best-fitting model yielded a pooled OR of 1.70 (95% CrI, 1.06-2.65; τ2 = 0.42), indicating a 70% increase in the odds of offspring depression for mothers who experienced antenatal or postnatal depression (Figure 2). The posterior probability (PP) that the pooled OR was greater than 1 was 98.6%; the posterior distribution for the pooled OR in Figure 3 provides a graphic summary of the association. Bayesian modeling assumptions for the present analysis were satisfied: posterior predictive checking supported the Gaussian outcome distribution for the OR, the scale reduction factor (Rhat) indicated good mixing of MCMC chains, and effective sample sizes were sufficient.

    Metaregression

    The association of perinatal depression timing (antenatal vs postnatal) with offspring depression was further explored using metaregression (ie, including a fixed effect of dichotomous timing). This metaregression did not include the study by Glasheen et al60 because of a lack of separation between antenatal and postnatal depression. Across the remaining 5 studies (in a sample size of 18 958 mother-child dyads), metaregression did not find strong evidence to support differences between antenatal and postnatal depression, observing only a 53.8% PP that the association of antenatal (compared with postnatal) depression with depression in offspring was greater than 1 (OR, 1.03; 95% CrI, 0.34-3.21; τ2 = 0.52).

    The percentage of female (relative to male) offspring was also explored using metaregression on all studies. This value was reported in each study and ranged from 40.6% to 55.8% female offspring. Metaregression indicated a 95.0% PP that the effect of percentage female offspring was greater than 1, such that a 1% increase in the percentage of female (relative to male) offspring was related to a 6% increase in the odds of offspring depression (OR, 1.06; 95% CrI, 0.99-1.14; τ2 = 0.31). Bayesian modeling assumptions were satisfied for each meta-regression analysis.

    Subgroup Analyses

    Follow-up subgroup analyses calculated the pooled OR across studies within each maternal depression period (4 antenatal studies, 14 693 mother-child dyads; 4 postnatal studies, 4265 mother-child dyads). A pooled OR of 1.78 (95% CrI, 0.93-3.33; τ2 = 0.31; PP [OR >1] = 96.2%) indicated a 78% increase in the odds of offspring depression for mothers with antenatal depression. A pooled OR of 1.66 (95% CrI, 0.65-3.84; τ2 = 1.00; PP [OR >1] = 88.0%) indicated a 66% increase in the odds of offspring depression for mothers with postnatal depression. Bayesian modeling assumptions for both subgroup analyses were satisfied. These subgroup analyses complemented the metaregression analyses: the subgroup analyses found that associations exist for both antenatal and postnatal depression, while the meta-regression indicates that these 2 associations are not different from one another.

    Publication Bias and Influence Analysis

    Visual inspection of funnel plot asymmetry did not indicate substantial evidence of publication bias, and the nonparametric trim-and-fill method found no missing studies (eFigure in the Supplement). However, formal testing (ie, Egger test) was not feasible given the small number of measured effect sizes. Omitting individual studies in turn from the meta-analysis (ie, the leave-one-out method) did not change inferences regarding the pooled OR. Influence analyses found a minimum 97.0% PP that the pooled OR was greater than 1 across models, with estimates for the pooled OR ranging from 1.55 to 1.90. This robustness is of particular importance in the present study given the highly discrepant sample sizes across studies; that is, in a multilevel model, the larger sample size studies could have overwhelmed the findings from the smaller studies, but they did not. A summary of the influence analysis is provided in Table 2 (pooled OR, 1.70; 95% CrI, 1.06-2.65).

    Discussion

    The results of the primary analysis found a 70% increased odds of depression in the offspring of mothers who experienced maternal depression during pregnancy. It supports the initial hypothesis that a maternal history of antenatal or postnatal depression is associated with an increased risk of offspring depression in adolescents and adults. Although metaregression analyses suggested that depression timing was not associated with model outcomes, subgroup analyses within each time (antenatal and postnatal) found a slightly higher pooled OR for the antenatal studies (78% increase in the odds of depression) than the postnatal studies (66% increase).

    A recent review80 reported that while 50% of women with antenatal depression and 30% of women with postnatal depression are diagnosed in the clinics, only 6% to 8% of them receive adequate treatment. Maternal depression during and after pregnancy has been associated with reduced growth rates, malnutrition, an increased risk of asthma and atopic diseases, childhood obesity, infections, and maltreatment in infancy and childhood.65 In addition to the poor physical health outcome itself being an independent risk factor, persistent depression in mothers increases the risk of early-onset depression in the offspring as a result of poor engagement and impaired ability to meet the child’s needs.66 One of our included studies (Plant et al43) reported on a direct trajectory between perinatal depression and childhood maltreatment as a mediating link for depression in young adults. While most teenagers recover from the first episode of depression, following recovery they are found to have a progressive or recurrent course into adulthood.67,68 Repeated or concurrent exposure to episodes of depression during adolescence significantly affects the chronicity of their illness.69 Therefore, targeted early interventions at different phases of development of depression will be required to reduce the cumulative effect of maternal depression, early life stressors, and repeated depressive episodes.

    Although the exact mechanism remains unclear, newer early life stress models in animals have shown some promising leads in understanding this risk transmission. Altered DNA methylation in the promoter regions of NR3C1 (OMIM 138040), BDNF (OMIM 113505), and epigenetic genes such as CRH (OMIM 122560), MECP2 (OMIM 300005), CNR1 (OMIM 114610), CRHR2 (OMIM 602034), and DLGAP2 (605438) have been implicated in the impaired stress response seen in adulthood as a result of maternal separation and maltreatment.70-73 Changes in the ESR1 gene expression, noted as early as in the first week of life because of lower maternal care, may influence multigenerational changes in maternal behavior and sensitivity.74 The increased odds reported in this study may partly reflect the transmission of genetic factors. It would be necessary in future studies to disentangle the extent to which the associations reported between perinatal depression and adolescent offspring psychopathology are environmentally as opposed to genetically mediated, given that the methods and potentials for intervention differ highly depending on the mechanisms involved.

    Our findings are also concordant with existing evidence of higher rates of depressive disorders in postpubertal adolescent girls. Several studies have attributed the increased risk of depression to negative body image, poor self-esteem, coping skills, or significant life events as well as possibly genetic heritability.75,76 A recent twin studies meta-analysis33 reported a depressive episode genetic heritability of about 40% in women (vs 34.4% in men). One study76 also suggested that the susceptible genes in female adolescents may affect the long-term stability of a depressive disorder diagnosis in adulthood.

    Given the heterogeneous nature of depression, we chose to study depressive symptoms in adolescents and young adults owing to the increased stability in the diagnosis and lesser ambiguity in the symptom spectrum.77 This study included only prospective longitudinal studies to minimize recall error, avoid selection bias, and provide more accuracy in establishing a temporal sequence. Furthermore, no evidence for publication bias was found in the included studies.

    Limitations

    This study does have some limitations. First, the inadvertent losses to follow-up in the included studies, especially the larger cohort studies, may have contributed to the results. However, studies such as Quarini et al42 have countered the issue by imputing the missing data for their primary analyses. While 2 of the remaining studies39,62 had very high retention rates for their subjects, 3 others43,60,61 reported mean retention rates of 82%, 85%, and 83% respectively. Second, a single standard diagnostic criterion for depression or major depressive disorder in both the mothers and offspring was not specified. For example, Taka-Eilola et al62 used a single structured question during antenatal visits for its 1966 birth cohort study due to the absence of specific screening scales at the time. Although this could be a potential limitation, it also makes the study more generalizable by being less dependent on a single diagnostic method. Third, while the lower age limit for inclusion was set at 12 years, the follow-up period varied in each of the studies included. This lack of homogeneity in offspring age at the time of follow-up assessments may have a potential confounding effect, in that studies with longer follow-up may report a higher incidence of depression. Fourth, the number of included studies (6) was relatively low and may inherently limit the precision of the obtained estimates. Fifth, the percentage of mothers with both antenatal and postnatal depression was not available for any of the studies. Therefore, the analysis cannot accurately address the possibility of unreported antenatal depression in a postnatal sample and/or unreported postnatal depression in an antenatal sample. Sixth, it should be noted that the effects of maternal depression may not be specific to that disorder. While participants with comorbid psychiatric diagnoses were excluded, subclinical symptoms of other psychiatric domains may be present and depression may also be representative of general susceptibility to psychopathology.78,79 Another possible limitation would be that of unpublished data not identified in our search strategy.

    Conclusions

    To our knowledge, this meta-analysis provides the most robust empirical evidence that maternal perinatal depression, especially antenatal depression, could play a substantial role in the onset of depression in adolescence and adulthood. Education about the benefits and risks of psychotherapy and medication approaches should be communicated to patients, families, and clinicians. Given the significant public health consequences of perinatal depression, a constant improvement in our screening efforts and management plans and optimal allocation of resources from public health initiatives are of utmost importance. Further explorative studies of the potential neurobiological and genetic pathways will remarkably improve our understanding of the complexities of depressive disorders. Specific studies designed to ascertain the evidence of postinterventional risk reduction in depression will aid in the development of future strategies to tackle this serious public health problem.

    Back to top
    Article Information

    Accepted for Publication: April 6, 2020.

    Published: June 30, 2020. doi:10.1001/jamanetworkopen.2020.8783

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Tirumalaraju V et al. JAMA Network Open.

    Corresponding Author: Sudhakar Selvaraj, MBBS, MRCPsych, DPhil, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX 77054 (sudhakar.selvaraj@uth.tmc.edu).

    Author Contributions: Drs Tirumalaraju and Suchting had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Tirumalaraju and Suchting contributed equally to this manuscript.

    Concept and design: Tirumalaraju, Suchting, Evans, Goetzl, Anand, Selvaraj.

    Acquisition, analysis, or interpretation of data: Tirumalaraju, Suchting, Refuerzo, Neumann, Anand, Ravikumar, Green, Cowen, Selvaraj.

    Drafting of the manuscript: Tirumalaraju, Suchting, Refuerzo, Anand, Selvaraj.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Suchting, Neumann, Anand, Green.

    Administrative, technical, or material support: Tirumalaraju, Evans, Goetzl, Anand, Selvaraj.

    Supervision: Refuerzo, Anand, Selvaraj.

    Conflict of Interest Disclosures: Dr Neumann reported receiving a grant from the Dutch Ministry of Education, Culture, and Science, a grant from the Netherlands Organization for Scientific Research Consortium on Individual Development, and a Canadian Institutes of Health Research team grant during the conduct of the study. Dr Selvaraj reported receiving speaking honoraria from Global Medical Education and honoraria from the British Medical Journal Publishing Group, owning shares at Flow Med Tech, and receiving research support from COMPASS outside the submitted work. Dr Evans reported receiving grants from University of Bristol during the conduct of the study. Dr Goetzl reported a pending patent for Isolation Fetal CNS Exosomes. No other disclosures were reported.

    Funding/Support: Dr Selvaraj is supported by the UTHealth faculty research supplement. The University of Texas Health Science Center at Houston research supplement funds were utilized for this study.

    Role of the Funder/Sponsor: The University of Texas Health Science Center at Houston had no 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.

    Additional Contributions: The authors thank Amy Taylor, MLS, liaison librarian at Texas Medical Center Library, Houston, for her guidance and invaluable support in building the search strategy.

    References
    1.
    Gaynes  BN, Gavin  N, Meltzer-Brody  S,  et al.  Perinatal depression: prevalence, screening accuracy, and screening outcomes.   Evid Rep Technol Assess (Summ). 2005;(119):1-8. doi:10.1037/e439372005-001PubMedGoogle Scholar
    2.
    Bennett  HA, Einarson  A, Taddio  A, Koren  G, Einarson  TR.  Prevalence of depression during pregnancy: systematic review.   Obstet Gynecol. 2004;103(4):698-709. doi:10.1097/01.AOG.0000116689.75396.5fPubMedGoogle ScholarCrossref
    3.
    Ko  JY, Rockhill  KM, Tong  VT, Morrow  B, Farr  SL.  Trends in postpartum depressive symptoms—27 states, 2004, 2008, and 2012.   MMWR Morb Mortal Wkly Rep. 2017;66(6):153-158. doi:10.15585/mmwr.mm6606a1PubMedGoogle ScholarCrossref
    4.
    Slomian  J, Honvo  G, Emonts  P, Reginster  J-Y, Bruyère  O.  Consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes.   Womens Health (Lond). 2019;15:1745506519844044. doi:10.1177/1745506519844044PubMedGoogle Scholar
    5.
    Mikšić  Š, Miškulin  M, Juranić  B, Rakošec  Ž, Včev  A, Degmečić  D.  Depression and suicidality during pregnancy.   Psychiatr Danub. 2018;30(1):85-90. doi:10.24869/psyd.2018.85PubMedGoogle ScholarCrossref
    6.
    Murray  L, Cooper  P, Fearon  P.  Parenting difficulties and postnatal depression: implications for primary healthcare assessment and intervention.   Community Pract. 2014;87(11):34-38.PubMedGoogle Scholar
    7.
    Fihrer  I, McMahon  CA, Taylor  AJ.  The impact of postnatal and concurrent maternal depression on child behaviour during the early school years.   J Affect Disord. 2009;119(1-3):116-123. doi:10.1016/j.jad.2009.03.001PubMedGoogle ScholarCrossref
    8.
    Thompson  SM, Jiang  L, Hammen  C, Whaley  SE.  Association of maternal depressive symptoms and offspring physical health in low-income families.   Matern Child Health J. 2018;22(6):874-882. doi:10.1007/s10995-018-2462-9PubMedGoogle ScholarCrossref
    9.
    Grace  SL, Evindar  A, Stewart  DE.  The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature.   Arch Womens Ment Health. 2003;6(4):263-274. doi:10.1007/s00737-003-0024-6PubMedGoogle ScholarCrossref
    10.
    Goodman  JH.  Paternal postpartum depression, its relationship to maternal postpartum depression, and implications for family health.   J Adv Nurs. 2004;45(1):26-35. doi:10.1046/j.1365-2648.2003.02857.xPubMedGoogle ScholarCrossref
    11.
    Betts  KS, Williams  GM, Najman  JM, Alati  R.  Maternal depressive, anxious, and stress symptoms during pregnancy predict internalizing problems in adolescence.   Depress Anxiety. 2014;31(1):9-18. doi:10.1002/da.22210PubMedGoogle ScholarCrossref
    12.
    Van Batenburg-Eddes  T, Brion  MJ, Henrichs  J,  et al.  Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study.   J Child Psychol Psychiatry. 2013;54(5):591-600. doi:10.1111/jcpp.12023PubMedGoogle ScholarCrossref
    13.
    Azeredo  CM, Santos  IS, Barros  AJD, Barros  FC, Matijasevich  A.  Maternal depression and bullying victimization among adolescents: results from the 2004 Pelotas cohort study.   Depress Anxiety. 2017;34(10):897-907. doi:10.1002/da.22662PubMedGoogle ScholarCrossref
    14.
    Capron  LE, Glover  V, Pearson  RM,  et al.  Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.   J Affect Disord. 2015;187:20-26. doi:10.1016/j.jad.2015.08.012PubMedGoogle ScholarCrossref
    15.
    Leis  JA, Heron  J, Stuart  EA, Mendelson  T.  Associations between maternal mental health and child emotional and behavioral problems: does antenatal mental health matter?   J Abnorm Child Psychol. 2014;42(1):161-171. doi:10.1007/s10802-013-9766-4PubMedGoogle ScholarCrossref
    16.
    Stein  A, Gath  DH, Bucher  J, Bond  A, Day  A, Cooper  PJ.  The relationship between postnatal depression and mother-child interaction.   Br J Psychiatry. 1991;158:46-52. doi:10.1192/bjp.158.1.46PubMedGoogle ScholarCrossref
    17.
    Kingston  D, Tough  S, Whitfield  H.  Antenatal and postpartum maternal psychological distress and infant development: a systematic review.   Child Psychiatry Hum Dev. 2012;43(5):683-714. doi:10.1007/s10578-012-0291-4PubMedGoogle ScholarCrossref
    18.
    Sullivan  PF, Neale  MC, Kendler  KS.  Genetic epidemiology of major depression: review and meta-analysis.   Am J Psychiatry. 2000;157(10):1552-1562. doi:10.1176/appi.ajp.157.10.1552PubMedGoogle ScholarCrossref
    19.
    Caspi  A, Moffitt  TE.  Gene-environment interactions in psychiatry: joining forces with neuroscience.   Nat Rev Neurosci. 2006;7(7):583-590. doi:10.1038/nrn1925PubMedGoogle ScholarCrossref
    20.
    Polderman  TJC, Benyamin  B, de Leeuw  CA,  et al.  Meta-analysis of the heritability of human traits based on fifty years of twin studies.   Nat Genet. 2015;47(7):702-709. doi:10.1038/ng.3285PubMedGoogle ScholarCrossref
    21.
    McAdams  TA, Rijsdijk  FV, Neiderhiser  JM,  et al.  The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.   Psychol Med. 2015;45(12):2583-2594. doi:10.1017/S0033291715000501PubMedGoogle ScholarCrossref
    22.
    Hannigan  LJ, Eilertsen  EM, Gjerde  LC,  et al.  Maternal antenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study.   Lancet Psychiatry. 2018;5(10):808-815. doi:10.1016/S2215-0366(18)30225-6PubMedGoogle ScholarCrossref
    23.
    Dagher  RK, Hofferth  SL, Lee  Y.  Maternal depression, pregnancy intention, and return to paid work after childbirth.   Womens Health Issues. 2014;24(3):e297-e303. doi:10.1016/j.whi.2014.03.002PubMedGoogle ScholarCrossref
    24.
    Kohlhoff  J, Barnett  B.  Parenting self-efficacy: links with maternal depression, infant behaviour, and adult attachment.   Early Hum Dev. 2013;89(4):249-256. doi:10.1016/j.earlhumdev.2013.01.008PubMedGoogle ScholarCrossref
    25.
    Prenoveau  J, Craske  M, Counsell  N,  et al.  Postpartum GAD is a risk factor for postpartum MDD: the course and longitudinal relationships of postpartum GAD and MDD.   Depress Anxiety. 2013;30(6):506-514. doi:10.1002/da.22040PubMedGoogle ScholarCrossref
    26.
    Beeber  LS, Schwartz  TA, Martinez  MI,  et al.  Depressive symptoms and compromised parenting in low-income mothers of infants and toddlers: distal and proximal risks.   Res Nurs Health. 2014;37(4):276-291. doi:10.1002/nur.21604PubMedGoogle ScholarCrossref
    27.
    O’Connor  TG, Tang  W, Gilchrist  MA, Moynihan  JA, Pressman  EK, Blackmore  ER.  Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study.   Biol Psychol. 2014;96:35-41. doi:10.1016/j.biopsycho.2013.11.002PubMedGoogle ScholarCrossref
    28.
    Glynn  LM, Howland  MA, Sandman  CA,  et al.  Antenatal maternal mood patterns predict child temperament and adolescent mental health.   J Affect Disord. 2018;228:83-90. doi:10.1016/j.jad.2017.11.065PubMedGoogle ScholarCrossref
    29.
    Rifkin-Graboi  A, Bai  J, Chen  H,  et al.  Antenatal maternal depression associates with microstructure of right amygdala in neonates at birth.   Biol Psychiatry. 2013;74(11):837-844. doi:10.1016/j.biopsych.2013.06.019PubMedGoogle ScholarCrossref
    30.
    Qiu  A, Shen  M, Buss  C,  et al; the GUSTO study group.  Effects of antenatal maternal depressive symptoms and socioeconomic status on neonatal brain development are modulated by genetic risk.   Cereb Cortex. 2017;27(5):3080-3092. doi:10.1093/cercor/bhx065PubMedGoogle ScholarCrossref
    31.
    Milgrom  J, Gemmill  AW, Bilszta  JL,  et al.  Antenatal risk factors for postnatal depression: a large prospective study.   J Affect Disord. 2008;108(1-2):147-157. doi:10.1016/j.jad.2007.10.014PubMedGoogle ScholarCrossref
    32.
    Robertson  E, Grace  S, Wallington  T, Stewart  DE.  Antenatal risk factors for postpartum depression: a synthesis of recent literature.   Gen Hosp Psychiatry. 2004;26(4):289-295. doi:10.1016/j.genhosppsych.2004.02.006PubMedGoogle ScholarCrossref
    33.
    McEwen  BS.  Effects of stress on the developing brain.   Cerebrum. 2011;2011:14.PubMedGoogle Scholar
    34.
    Azar  R, Mercer  D.  Mild depressive symptoms are associated with elevated C-reactive protein and proinflammatory cytokine levels during early to midgestation: a prospective pilot study.   J Womens Health (Larchmt). 2013;22(4):385-389. doi:10.1089/jwh.2012.3785PubMedGoogle ScholarCrossref
    35.
    Achtyes  E, Keaton  SA, Smart  L,  et al.  Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression.   Brain Behav Immun. 2020;83:239-247. doi:10.1016/j.bbi.2019.10.017PubMedGoogle ScholarCrossref
    36.
    Osborne  S, Biaggi  A, Chua  TE,  et al.  Antenatal depression programs cortisol stress reactivity in offspring through increased maternal inflammation and cortisol in pregnancy: the Psychiatry Research and Motherhood–Depression (PRAM-D) Study.   Psychoneuroendocrinology. 2018;98:211-221. doi:10.1016/j.psyneuen.2018.06.017PubMedGoogle ScholarCrossref
    37.
    Pearson  RM, Evans  J, Kounali  D,  et al.  Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.   JAMA Psychiatry. 2013;70(12):1312-1319. doi:10.1001/jamapsychiatry.2013.2163PubMedGoogle ScholarCrossref
    38.
    Pawlby  S, Hay  DF, Sharp  D, Waters  CS, O’Keane  V.  Antenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based study.   J Affect Disord. 2009;113(3):236-243. doi:10.1016/j.jad.2008.05.018PubMedGoogle ScholarCrossref
    39.
    Murray  L, Arteche  A, Fearon  P, Halligan  S, Goodyer  I, Cooper  P.  Maternal postnatal depression and the development of depression in offspring up to 16 years of age.   J Am Acad Child Adolesc Psychiatry. 2011;50(5):460-470. doi:10.1016/j.jaac.2011.02.001PubMedGoogle ScholarCrossref
    40.
    Netsi  E, Pearson  RM, Murray  L, Cooper  P, Craske  MG, Stein  A.  Association of persistent and severe postnatal depression with child outcomes.   JAMA Psychiatry. 2018;75(3):247-253. doi:10.1001/jamapsychiatry.2017.4363PubMedGoogle ScholarCrossref
    41.
    Hay  DF, Pawlby  S, Waters  CS, Sharp  D.  Antepartum and postpartum exposure to maternal depression: different effects on different adolescent outcomes.   J Child Psychol Psychiatry. 2008;49(10):1079-1088. doi:10.1111/j.1469-7610.2008.01959.xPubMedGoogle ScholarCrossref
    42.
    Quarini  C, Pearson  RM, Stein  A, Ramchandani  PG, Lewis  G, Evans  J.  Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?   J Affect Disord. 2016;189:329-335. doi:10.1016/j.jad.2015.09.039PubMedGoogle ScholarCrossref
    43.
    Plant  DT, Pariante  CM, Sharp  D, Pawlby  S.  Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment.   Br J Psychiatry. 2015;207(3):213-220. doi:10.1192/bjp.bp.114.156620PubMedGoogle Scholar
    44.
    Hammerton  G, Mahedy  L, Mars  B,  et al.  Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation.   PLoS One. 2015;10(7):e0131885. doi:10.1371/journal.pone.0131885PubMedGoogle Scholar
    45.
    Hammen  C, Brennan  PA.  Severity, chronicity, and timing of maternal depression and risk for adolescent offspring diagnoses in a community sample.   Arch Gen Psychiatry. 2003;60(3):253-258. doi:10.1001/archpsyc.60.3.253PubMedGoogle Scholar
    46.
    Tomlinson  M, Rotheram-Borus  MJ, Scheffler  A, le Roux  I.  Antenatal depressed mood and child cognitive and physical growth at 18-months in South Africa: a cluster randomised controlled trial of home visiting by community health workers.   Epidemiol Psychiatr Sci. 2018;27(6):601-610. doi:10.1017/S2045796017000257PubMedGoogle Scholar
    47.
    Verkuijl  NE, Richter  L, Norris  SA, Stein  A, Avan  B, Ramchandani  PG.  Postnatal depressive symptoms and child psychological development at 10 years: a prospective study of longitudinal data from the South African Birth to Twenty cohort.   Lancet Psychiatry. 2014;1(6):454-460. doi:10.1016/S2215-0366(14)70361-XPubMedGoogle Scholar
    48.
    Pietikäinen  JT, Kiviruusu  O, Kylliäinen  A,  et al.  Maternal and paternal depressive symptoms and children’s emotional problems at the age of 2 and 5 years: a longitudinal study.   J Child Psychol Psychiatry. 2020;61(2):195-204. doi:10.1111/jcpp.13126PubMedGoogle Scholar
    49.
    Ouzzani  M, Hammady  H, Fedorowicz  Z, Elmagarmid  A.  Rayyan—a web and mobile app for systematic reviews.   Syst Rev. 2016;5(1):210. doi:10.1186/s13643-016-0384-4PubMedGoogle Scholar
    50.
    Jaworska  N, MacQueen  G.  Adolescence as a unique developmental period.   J Psychiatry Neurosci. 2015;40(5):291-293. Published correction appears in  J Psychiatry Neurosci. 2015;40(6):386. doi:10.1503/jpn.150268PubMedGoogle Scholar
    51.
    Viechtbauer  W.  Conducting meta-analyses in R with the metafor package.   J Stat Softw. 2010;36(1):1-48. doi:10.18637/jss.v036.i03PubMedGoogle Scholar
    52.
    Bürkner  P-C.  Advanced Bayesian multilevel modeling with the R package brms.   R Journal. 2018;10(1):395-411. doi:10.32614/RJ-2018-017Google Scholar
    53.
    R Core Team.  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2019.
    54.
    Harrer  M, Cuijpers  P, Furukawa  TA, Ebert  DD.  Doing meta-analysis in R: a hands-on guide. Published 2019. Accessed May 12, 2020. doi:10.5281/zenodo.2551803
    55.
    Williams  DR, Rast  P, Bürkner  P-C.  Bayesian meta-analysis with weakly informative prior distributions.  January 2018. doi:10.31234/https://osf.io/7tbrm
    56.
    McElreath  R.  Statistical Rethinking: A Bayesian Course with Examples in R and Stan. CRC Press; 2016.
    57.
    Gelman  A, Jakulin  A, Pittau  MG, Su  Y-S.  A weakly informative default prior distribution for logistic and other regression models.   Ann Appl Stat. 2008;2(4):1360-1383. doi:10.1214/08-AOAS191Google Scholar
    58.
    Bürkner  P-C, Williams  DR, Simmons  TC, Woolley  JD.  Intranasal oxytocin may improve high-level social cognition in schizophrenia, but not social cognition or neurocognition in general: a multilevel Bayesian meta-analysis.   Schizophr Bull. 2017;43(6):1291-1303. doi:10.1093/schbul/sbx053PubMedGoogle Scholar
    59.
    Chang  BH, Hoaglin  DC.  Meta-analysis of odds ratios: current good practices.   Med Care. 2017;55(4):328-335. doi:10.1097/MLR.0000000000000696PubMedGoogle Scholar
    60.
    Glasheen  C, Richardson  GA, Kim  KH, Larkby  CA, Swartz  HA, Day  NL.  Exposure to maternal pre- and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring.   Dev Psychopathol. 2013;25(4 Pt 1):1045-1063. doi:10.1017/S0954579413000369PubMedGoogle Scholar
    61.
    Raposa  E, Hammen  C, Brennan  P, Najman  J.  The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.   J Adolesc Health. 2014;54(1):88-93. doi:10.1016/j.jadohealth.2013.07.038PubMedGoogle Scholar
    62.
    Taka-Eilola Nèe Riekki  T, Veijola  J, Murray  GK, Koskela  J, Mäki  P.  Severe mood disorders and schizophrenia in the adult offspring of antenatally depressed mothers in the Northern Finland 1966 Birth Cohort: relationship to parental severe mental disorder.   J Affect Disord. 2019;249:63-72. doi:10.1016/j.jad.2019.02.011PubMedGoogle Scholar
    63.
    Stroup  DF, Berlin  JA, Morton  SC,  et al; Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group.  Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting.   JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008PubMedGoogle Scholar
    64.
    Wells  GA, Shea  B, O’Connell  D,  et al.  The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses.  Published 2012. Accessed May 12, 2020. http://wwwohrica/programs/clinical_epidemiology/oxford.asp
    65.
    Pierce  M, Hope  HF, Kolade  A,  et al  Effects of parental mental illness on children's physical health: systematic review and meta-analysis.   Br J Psychiatry. 2019;Oct 15:1-10. doi:10.1192/bjp.2019.216Google Scholar
    66.
    Dietz  LJ, Birmaher  B, Williamson  DE,  et al.  Mother-child interactions in depressed children and children at high risk and low risk for future depression.   J Am Acad Child Adolesc Psychiatry. 2008;47(5):574-582. doi:10.1097/CHI.0b013e3181676595PubMedGoogle Scholar
    67.
    Lewinsohn  PM, Rohde  P, Klein  DN, Seeley  JR.  Natural course of adolescent major depressive disorder: I. continuity into young adulthood.   J Am Acad Child Adolesc Psychiatry. 1999;38(1):56-63. doi:10.1097/00004583-199901000-00020PubMedGoogle Scholar
    68.
    Harrington  R, Fudge  H, Rutter  M, Pickles  A, Hill  J.  Adult outcomes of childhood and adolescent depression. I. Psychiatric status.   Arch Gen Psychiatry. 1990;47(5):465-473. doi:10.1001/archpsyc.1990.01810170065010PubMedGoogle Scholar
    69.
    Davidovich  S, Collishaw  S, Thapar  AK, Harold  G, Thapar  A, Rice  F.  Do better executive functions buffer the effect of current parental depression on adolescent depressive symptoms?   J Affect Disord. 2016;199:54-64. doi:10.1016/j.jad.2016.03.049PubMedGoogle Scholar
    70.
    Kember  RL, Dempster  EL, Lee  THA, Schalkwyk  LC, Mill  J, Fernandes  C.  Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse.   Brain Behav. 2012;2(4):455-467. doi:10.1002/brb3.69PubMedGoogle Scholar
    71.
    Elliott  E, Ezra-Nevo  G, Regev  L, Neufeld-Cohen  A, Chen  A.  Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice.   Nat Neurosci. 2010;13(11):1351-1353. doi:10.1038/nn.2642PubMedGoogle Scholar
    72.
    Chertkow-Deutsher  Y, Cohen  H, Klein  E, Ben-Shachar  D.  DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2.   Int J Neuropsychopharmacol. 2010;13(3):347-359. doi:10.1017/S146114570999071XPubMedGoogle Scholar
    73.
    Franklin  TB, Russig  H, Weiss  IC,  et al.  Epigenetic transmission of the impact of early stress across generations.   Biol Psychiatry. 2010;68(5):408-415. doi:10.1016/j.biopsych.2010.05.036PubMedGoogle Scholar
    74.
    Peña  CJ, Neugut  YD, Champagne  FA.  Developmental timing of the effects of maternal care on gene expression and epigenetic regulation of hormone receptor levels in female rats.   Endocrinology. 2013;154(11):4340-4351. doi:10.1210/en.2013-1595PubMedGoogle Scholar
    75.
    Angold  A, Costello  EJ, Erkanli  A, Worthman  CM.  Pubertal changes in hormone levels and depression in girls.   Psychol Med. 1999;29(5):1043-1053. doi:10.1017/S0033291799008946PubMedGoogle Scholar
    76.
    Silberg  J, Pickles  A, Rutter  M,  et al.  The influence of genetic factors and life stress on depression among adolescent girls.   Arch Gen Psychiatry. 1999;56(3):225-232. doi:10.1001/archpsyc.56.3.225PubMedGoogle Scholar
    77.
    Carlson  GA.  The challenge of diagnosing depression in childhood and adolescence.   J Affect Disord. 2000;61(suppl 1):3-8. doi:10.1016/S0165-0327(00)00283-4PubMedGoogle Scholar
    78.
    Tackett  JL, Lahey  BB, van Hulle  C, Waldman  I, Krueger  RF, Rathouz  PJ.  Common genetic influences on negative emotionality and a general psychopathology factor in childhood and adolescence.   J Abnorm Psychol. 2013;122(4):1142-1153. doi:10.1037/a0034151PubMedGoogle Scholar
    79.
    Caspi  A, Houts  RM, Belsky  DW,  et al.  The p factor: one general psychopathology factor in the structure of psychiatric disorders?   Clin Psychol Sci. 2014;2(2):119-137. doi:10.1177/2167702613497473PubMedGoogle Scholar
    80.
    Cox  EQ, Sowa  NA, Meltzer-Brody  SE, Gaynes  BN.  The perinatal depression treatment cascade: baby steps toward improving outcomes.   J Clin Psychiatry. 2016;77(9):1189-1200. doi:10.4088/JCP.15r10174PubMedGoogle Scholar
    ×