Beyond the postpartum period

Numerous studies of the impact of maternal depression have not exclusively focused on perinatal or postpartum depression. Maternal depression has consistently been shown to be associated with a negative impact not only on the infant but also on the prepubescent, adolescent and adult offspring (Tronick and Reck, Reference Tronick and Reck2009; Goodman and Garber Reference Goodman and Garber2017; Stein et al., Reference Stein, Pearson, Goodman, Rapa, Rahman, McCallum, Howard and Pariante2014; Weissman et al., Reference Weissman, Berry, Warner, Gameroff, Skipper, Talati, Pilowesky and Wickramarante2016; Hammen, Reference Hammen2018; Weissman, Reference Weissman2018). These effects are sustained in offspring followed into adulthood especially when parental depression persists over long periods (Stein et al., Reference Stein, Pearson, Goodman, Rapa, Rahman, McCallum, Howard and Pariante2014; Netsi et al., Reference Netsi, Pearson, Murray, Cooper, Craske and Stien2018; Santavirta et al., Reference Santavirta, Santavirta and Gilman2018). The effects include low birth weights, poor school performance, increased health complications, depression, anxiety, substance abuse, increased suicidal behavior and increased mortality (Liu et al., Reference Liu, Daumit, Dua, Aquila, Charlson, Cuijpers, Druss, Dudek, Freeman, Fuji, Gaebel, Hegerl, Levay, Laursen, Ma, Maj, Medina-Mora, Nordentoft, Prabhakaran, Pratt, Prince, Rangaswamy, Shiers, Susser, Thornicroft, Wahlbeck, Wassie, Whiteford and Saxena2017; Ramming et al., Reference Ramming, Benros, Thorup, Davidsen, Hjorthoj, Nordentoft, Laursen and Sorensen2019). Paternal effects have been studied less than maternal but have also been found (Kerstis et al., Reference Kerstis, Aarts, Tillman, Persson, Engstrom, Edlund, Ohrvik and Skalkidou2016; Sweeney and MacBeth, Reference Sweeney and MacBeth2016). The Shen et al. (Reference Shen, Magnusson, Rai, Lundberg, Le-Scherban, Dalman and Lee2016) study from Sweden had sufficiently large samples of fathers and was longitudinal and did show both a maternal and paternal depression effect on child's school performance. It has usually been unclear whether the father was actually living in the home or had much contact with the child in these studies.

Mother–infant bonding and parental bonding

Studies of the impact of maternal depression beyond the postpartum period with children beyond infancy have also examined measures of mother/child attachment. Here a frequently used scale is the Parental Bonding Instrument (PBI). Developed by Gordon Parker in the 1970s in Australia, the PBI measures the offspring's perception of the parenting they received up to age 16 as well as the parent's perception of their parenting. It measures dimensions of care and protection in four quadrants – high care/low control; high care/high control; low care/high control; low care/low control with 1 and 4 going from optimal to neglectful parenting. The PBI assessment seems to be an extension for older children of the mother–infant bonding scale. The PBI has survived many tests and years and remains an important clinical moderator of outcomes in intergenerational research nearly 45 years after it was introduced (Parker et al., Reference Parker, Tupling and Brown1979; Wilhelm et al., Reference Wilhelm, Niven, Parker and Hadzi-Pavlovic2004). Studies of mother/infant bonding and parental bonding need to be joined in longitudinal studies. We could not find one study that examined whether mother/infant bonding assessed during infancy predicted later parental bonding problems arising when the infants were prepubescent to adolescents. Both study attachment and have been shown to be powerful moderators of the relationship between mothers and children, and could be potential targets for intervention and also for understanding resilience.

Intergenerational study of biological mechanisms

Parental bonding is only one of the potential moderators. A recent comprehensive review of the possible mechanisms accounting for the negative effects of intergenerational transmission of depression on offspring noted the clinical link may be confounded or moderated by genetics, maternal childhood maltreatment or use of antidepressants during pregnancies (Sawyer et al., Reference Sawyer, Zunszain, Dazzan and Pariante2019). Many biological mechanisms also can explain how an adverse intra-uterine environment influenced by behavior can predispose to disorders later in life. These mechanisms include inflammation, epigenetic regulation, development of brain structure and placental mechanisms regulating the stress hormones to the fetus. The Sawyer et al. (Reference Sawyer, Zunszain, Dazzan and Pariante2019) article is highly recommended to the reader to understand the novelty, complexity and challenge of the study of brain/behavior biologic mechanisms. They conclude that at least three parallel molecular pathways operate across the two generations and include epigenetic and biomarker changes in the oxytocin, glucocorticoids and inflammation systems. Their review supports the importance of intergenerational study of mother and children also assessed prospectively.

Opportunities for preventive interventions

Until understanding of the biological mechanisms provides new insights, how do you translate into prevention and treatment the strong clinical evidence on the transmission of intergenerational depression? There is good evidence that successful treatment of a depressed mother, meaning reduction of her depressive symptoms, has positive effects on her school-aged and adolescent children (Cuijpers et al., Reference Cuijpers, Weitz, Karyotaki, Garber and Andersson2015; Weissman et al., Reference Weissman, Wickramaratne, Pilowsky, Poh, Batten, Hernandez, Flament, Stewart, McGrath, Blier and Stewart2015). These effects can be sustained at least for a year after remission (Wickramaratne et al., Reference Wickramaratne, Gameroff, Pilowsky, Hughes, Garber, Mallow, King, Cerda, Sood, Alpert, Trivedi, Fava, Rush, Wisniewski and Weissman2011). The effect on offspring has been shown in trials treating depressed mothers with medication (Weissman et al., Reference Weissman, Pilowsky, Wickramante, Talati, Wisniewski, Fava, Hughes, Garber, Mallow, King, Cerda, Sood, Alpert, Trivedi and Rush2006; Reference Weissman, Wickramaratne, Pilowsky, Poh, Batten, Hernandez, Flament, Stewart, McGrath, Blier and Stewart2015) or psychotherapy (Swartz et al., Reference Swartz, Cyranowski, Cheng, Zuckoff, Brent, Markowitz, Martin, Amole, Ritchey and Frank2016, Grote et al., Reference Grote, Simon, Russo, Lohr, Carson and Katon2017). The key component seems to be optimally delivered therapy reducing the symptoms of maternal depression. It is not yet clear whether parenting interventions are needed in addition to treatment of depression (Howard and Challacombe, Reference Howard and Challacombe2018), or should be routinely offered as integrated interventions (Goodman and Garber, Reference Goodman and Garber2017). Certainly parenting approaches may help with improving mother/infant bonding perhaps combined with treatment of maternal depression.

Since the effects of maternal depression can be seen early in the offspring, there is need for the earliest possible screening and treatment in pregnancy. In February 2019 the U.S. Preventive Task Force noted that an estimated 400 000 American mothers each year and up to 13% worldwide experience perinatal depression. They issued a report on the prevention of perinatal depression in pregnant women at high risk for depression (O'Connor et al., Reference O'Connor, Senger, Henniger, Copppola and Gaynes2019). They reviewed 50 clinical trials including psychotherapy, antidepressants, complementary and alternative medicine. Their review found about a 50% reduction in perinatal depression using cognitive behavioral or interpersonal psychotherapy adapted for the perinatal period in women at high risk for depression. The high risk definition was based on symptoms, history of depression or socio-economic factors. The task force concluded that providing or referring pregnant women at increased risk to these counseling interventions had a moderate real benefit in preventing perinatal depression. They also noted that a variety of other interventions provides some evidence of effectiveness but lacked a robust evidence base and needs further research.

Pregnancy presents additional challenges for maternal treatment. Medications are widely used and available and effective for reducing depression. Evidence for the effect of in utero exposure to serotonin selective reuptake inhibitors suggests caution in their role during pregnancy (Gingrich et al., Reference Gingrich, Malm, Ansorge, Brown, Sourander, Deepika, Teixeira, Caffrey Cagliostro, Mahadevia and Weissman2017). These studies are by need observational and are subject to confounding of maternal depression severity as well as the fact that maternal depression itself with or without maternal treatment has an effect on the developing fetus. One recent study based on a large Finnish birth cohort followed up to 14 years found increased motor and language development problems prepubertally (Brown et al., Reference Brown, Gyllenberg, Malm, McKeague, Hinkka-Yli-Salomäki, Artama, Gissler, Cheslack-Postava, Weissman, Gingrich and Sourander2016) and depression in early adolescence in offspring (Malm et al., Reference Malm, Brown, Gissler, Gyllenberg, Hinkka-Yli-Salomäki, McKeague, Weissman, Wickramaratne, Artama, Gingrich and Sourander2016). This is an area of intense public health interest and a number of investigations are currently underway. Included are studies of the effect of pre-natal Selective Seratonin Reuptake Inhibitors (SSRI) exposure to brain development using structural and diffusion magnetic resonance imaging (Lugo-Candelas et al., Reference Lugo-Candelas, Cha, Hong, Bastidas, Weissman, Flfer, Myers, Talati, Bansal, Peterson, Monk, Gingrich and Posner2018). Discussions of depression treatment during pregnancy must include consideration of the impact of untreated depression especially for women who do not respond to non-pharmacologic interventions (Molyneaux et al., Reference Molyneaux, Trevillion and Howard2015).

The Kasamatsu et al. (Reference Kasamatsu, Tsuchida, Matsumura, Shimao, Hamazaki and Inadera2019) findings on the intergenerational effect of maternal depression of mother/infant bonding join studies from USA, UK, Sweden, Denmark, Finland and Australia including different age groups of children; different timings of maternal depression, different moderators and different mechanisms of outcomes and a convergence of findings. There are many new opportunities for prevention and for improved care. It is clear that intergenerational studies that prospectively follow the generations are a fruitful strategy for clinical and biological research in depression.