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Cumulative Effects of Prenatal and Concurrent Maternal Distress on Psychiatric Disorders in Adolescent Offspring

Abstract

Rationale: Offspring exposure to maternal distress prenatally, as well as in adolescence have independently been linked to offspring psychopathology. However, the cumulative effect of these exposures on adolescent mental health is not well understood.

Methods: 1964 participants enrolled in the 2014 Ontario Child Health Study (OCHS) aged 12-17 years completed the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Maternal prenatal distress was defined as self-reported depression and/or anxiety during pregnancy requiring treatment. Maternal concurrent distress was self-reported when offspring were 12-17 years of age using the Kessler Psychological Distress Scale (K6). We examined associations between increasing levels of exposure to maternal distress (no exposure, prenatal exposure, concurrent exposure, both prenatal and concurrent exposure) and the risk of psychiatric disorders in 12-17 year-olds. Analyses were adjusted for age, sex, socioeconomic status, family functioning, single-parent status and parental physical health.

Results: The odds of major depressive disorder (OR=1.29, 95% CI: 1.01- 1.67) and ADHD (OR=1.30, 95% CI: 1.02-1.65) increased with increasing exposure to maternal distress. The adverse effects of increasing levels of maternal distress were found to be amplified in males for adolescent major depressive disorder, social anxiety disorder, and generalized anxiety disorder.

Conclusion: Increasing exposure to maternal distress is associated with an increased risk of major depressive disorder and ADHD in adolescent offspring in a dose-dependent manner. These results highlight the importance of the early identification of maternal distress, and ongoing monitoring and intervention upon its causes in order to reduce the burden of mental disorders in adolescents.

Introduction

Mothers have a profound impact on their children’s health and development across the lifespan. For example, the experience of maternal distress (e.g., stress, anxiety, depression) can have lifelong adverse effects on offspring mental health (Brand & Brennan, 2009). Indeed, one of the strongest predictors of psychopathology in offspring is the experience of maternal distress during childhood (Goodman et al, 2011) and/or adolescence, as it increases the risk of both externalizing (e.g., impulsivity, aggression) and internalizing (e.g., depression, anxiety) problems across the lifespan (Nelson et al, 2003; Campbell et al, 2009). Despite these findings, surprisingly few studies have examined the joint effect of maternal distress experienced prenatally as well as during childhood or adolescence.

Mental disorders affect 20% of children and adolescents globally (Kieling et al, 2011), and predict some of the most chronic and costly problems faced by health systems and society (Silbernagel & Davidson, 2017). For example, adolescent mental health problems are associated with more difficulties in family and peer relationships (Patel et al, 2007), reduced academic performance (Avenevoli, 2008), and poorer vocational attainment (Wille et al, 2008). Studies suggest that 50% of adult mental disorders have their precursors during adolescence (Kim-Cohen et al, 2003), further highlighting the importance of identifying modifiable risk factors for adolescent psychopathology (Belfer, 2008).

Up to 30% of women experience some form of distress during pregnancy (Fontein-Kuipers, 2016). Prenatal maternal distress predicts mental health problems in offspring during childhood and adolescence (Lewis et al, 2014; O’Donnell & Meaney, 2017). Maternal depression during pregnancy increases the risk of emotional problems in children and adolescents by up to two-to-three times (Weissman et al, 2006; Kovacs et al, 1997). Although fewer studies have explored the long-term effects of maternal antenatal anxiety, O’Conner et al (2002) have also linked maternal anxiety in pregnancy to behavioural and emotional problems in childhood.

Maternal distress experienced during adolescence also has been associated with offspring psychopathology, as distressed mothers struggle to attend to all of the needs of their adolescents (Naicker et al, 2012). This has been linked to increased levels of punitive parenting practices and reduced maternal sensitivity (Dix & Meunier, 2009), which in turn predict adolescent maladjustment (Rubin & Burgess, 2002) and externalizing and internalizing problems (Bradley & Corwyn, 2007). Adolescent mental health problems can also contribute to maternal distress, resulting in a deleterious cycle of psychopathology among members of the dyad (Middeldorp et al, 2016).

Studies have consistently reported that males and females may differ in their susceptibility to maternal prenatal and postnatal distress (McGinnis et al, 2015). For example, Quarini and colleagues (2016) reported that females are more susceptible to prenatal maternal distress, whereas males may be more susceptible to postnatal maternal distress. However, another study by Geradin and colleagues (2011) reported that males may be more vulnerable to both prenatal and postnatal maternal distress. This difference in gender susceptibility may be due to a male’s genetic vulnerability, and/or because of differential environmental exposures including parenting behaviors (e.g., mothers tend to interact less responsively with their sons than their daughters (Mirhosseini et al, 2015)). However, findings on moderation by sex are relatively limited and sometimes inconsistent because of differences in study methods (Essex et al, 2002; McKee et al, 2007).

Despite our knowledge of the individual contributions of maternal prenatal distress, and of distress experienced by mothers when their offspring are adolescents, very little is known about the joint effects of maternal distress at these two important developmental time points on adolescent mental health. Indeed, researchers such and Davis et al (2019) and Naicker et al (2012) have examined adolescent mental health as a result of either prenatal or postnatal maternal distress, but not both. Previous studies that have examined the combined effect of maternal distress at more than one time point have primarily focused on maternal distress during similar developmental epochs. For example, many studies have examined the cumulative effect of prenatal and early postnatal maternal distress on young children (Wen et al, 2017; Gjerde et al, 2017; Brand & Brennan, 2007). While, the current literature highlights the importance of examining maternal distress prenatally and concurrently in adolescence in order to better understand the development of adolescent mental disorders and how to intervene to optimize mental health in mothers and their adolescent offspring, our understanding of the cumulative effects of maternal distress over time remains incomplete. To address these shortcomings, we examined the cumulative effect of maternal prenatal and concurrent distress on adolescent mental health.

Methods

Sample

Participants in this study were drawn from the 2014 Ontario Child Health Study (OCHS), a province-wide, cross-sectional epidemiologic study that gathered data from 10,802 participants aged 4-17 and their families to estimate the prevalence of youth mental illness in Ontario, Canada. The 2014 OCHS utilizes clustered, stratified, random sampling techniques to generate a study sample representative of the over two million children and youth currently residing in Ontario, Canada (Duncan et al, 2018). A subsample of 1964 adolescents aged 12-17 completed the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Household-level sampling in the MINI-KID subsample was performed whereby only one eligible adolescent was randomly selected per household to complete the MINI-KID. This was designed to reduce bias by over-representing families with larger numbers of children aged 12-17.

Outcome: MINI-KID

The MINI-KID is a structured diagnostic interview that detects current (past 6 month) DSM-IV psychiatric disorders in the pediatric population. The MINI-KID demonstrates excellent convergent and discriminant validity that is comparable to other gold-standard psychiatric interviews (Duncan et al., 2017), as well as strong reliability and concordance with the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) (Sheehan et al., 2010). Because the goal of the 2014 OCHS was to establish prevalence rates for the most common pediatric psychiatric disorders (those that have the potential to have largest impact at a population level), symptoms of the following MINI-KID diagnoses were assessed: major depressive disorder, separation anxiety disorder, social anxiety disorder, specific phobia, generalized anxiety disorder, oppositional defiant disorder, conduct disorder and attention-deficit/hyperactivity disorder.

The MINI-KID was administered by Statistics Canada personnel who were experienced in conducting clinical research involving children and held undergraduate or graduate level degrees in the health sciences or the social sciences. Interview administrators received training on interview techniques as well as the symptom criteria and clinical foundations of the disorders being measured by the MINI-KID, and were naïve to the maternal mental health of the participants they interviewed.

Maternal Prenatal Distress: Depression/Anxiety Requiring Treatment During Pregnancy

Distress is a broad construct consisting of emotional and other psychiatric symptoms like anxiety and depression (Carlson et al 2010), a definition commonly used to define this construct in mothers in the past (i.e., symptoms of depression and anxiety (e.g., Kingston et al, 2012; Ewon et al, 2013; Riis et al, 2016)). Maternal prenatal anxiety and depression were assessed retrospectively via self-report as part of the 2014 OCHS. Mothers were asked if “during the pregnancy with [selected child], did you have depression or anxiety that required you to take prescription medication for more than two weeks or to receive special care (for example, early admission to hospital, added physician visits, bed rest)?”. This question was based on the Canadian Maternity Experiences Questionnaire (CME, Public Health Agency of Canada, 2009) and the CDC Pregnancy Risk Assessment Monitoring System 6 (PRAMS-6, Public Health Agency of Canada, 2018). The anxiety/depression items on the PRAMS-6 were among the best performing items on the scale (Davis et al, 2013).

Maternal Concurrent Distress Adolescent Assessment: K6 Distress Scale

Concurrent maternal depression/anxiety was assessed using the Kessler K6 psychological distress scale. This self-report instrument assesses past-month symptoms of stress and distress to identify individuals who are experiencing significant functional and daily-life challenges due to mental illness (Wittchen, 2010). Factor analysis identifies a two-factor construct of depression and anxiety to optimally describe the symptom structure of the K6 (Lace et al., 2018). The K6 demonstrates strong concordance with the Composite International Diagnostic Interview (CIDI) “any serious mental illness” module and has been extensively validated in diverse populations (Prochaska, Sung, Max, Shi, & Ong, 2012).

The Importance of Measuring Maternal Distress Prenatally and Concurrently

We considered the impact of prenatal and concurrent distress time points separately on offspring psychopathology in adolescence, as well as jointly in order to develop a better understanding of the association between time and cumulative distress ‘dosage’ on adolescent outcomes. Schetter (2011) reported that both the type and duration of distress can impact offspring outcomes, and DiPietro and colleagues (2006) highlighted that distress occurring over time impacts offspring development more than its less frequent or chronic experience. The examination of maternal distress both prenatally and concurrently can also provide insights into the need and optimal timing for interventions applied to optimize both maternal and offspring mental health (Cicchetti and Gunnar, 2008).

Covariates

Age, sex and socioeconomic disadvantage: Because sex influences mental illness prevalence throughout childhood and adolescence (Kessler et al., 2007), as well as the type and severity (Becker, McClellan, & Reed, 2016; Sramek, Murphy, & Cutler, 2016), we adjusted for it in our statistical analyses. Socioeconomic status is also an independent predictor of youth mental health (Bradley & Corwyn, 2002), and can influence maternal mental health and the experience of distress during (Goyal, Gay, & Lee, 2010) and after pregnancy (Belle, 1990). We used the Statistics Canada’s Low-Income Measurement (LIM) cut-off to define socioeconomic disadvantage in this study. This measure is a percentage of median adjusted household income, accounting for household needs based on region and family size (Wolfson, 1992).

Family Functioning: Because family dysfunction affects and can be caused by psychopathology in youth (Jozefiak & Wallander, 2016; Krug, Wittchen, Lieb, Beesdo-Baum, & Knappe, 2016), and also influences maternal distress (Fleck et al., 2015; Sheck, 1998), we adjusted for family function assessed using the General Functioning (GF) subscale of the McMaster Family Assessment Device (Epstein, Baldwin, & Bishop, 1983).

Single Parent Household: As the responsibilities of parenting are significantly greater for single parents, and since this can contribute to greater distress in parents (Cairney, Boyle, Offord, & Racine, 2003), and mental illness in offspring (Fergusson et al, 2007), we also adjusted for this variable in our adjusted analyses.

Parental Physical Health: Chronic physical health problems represent an additional source of stress and adversity for parents that can influence maternal mental health (McMahon, 2014) and the mental health of their children (Sieh, Dikkers, Visser-Meily, & Meijer, 2012). Because of this, we included parental-self report of chronic physical health problems (for instance: diabetes, epilepsy or cardiovascular disease) in our adjusted analyses.

Statistical Analyses

Participants were classified into four groups based on increasing exposure to maternal distress: no exposure to either prenatal or concurrent maternal distress (reference group/group 1), exposure to only prenatal distress (group 2), exposure to only concurrent maternal distress (group 3), or exposure to both prenatal and concurrent maternal distress (group 4). This classification structure allows us to estimate the magnitude of risk for youth psychopathology attributable to either prenatal or concurrent maternal distress, as well as the cumulative effect of these two exposures.

Demographic information was compared between groups using t-tests (continuous data) and Chi squared–tests (categorical data). To assess the difference in prevalence of MINI-KID diagnoses across these four groups, logistic regression analyses were performed to generate odds ratios estimating the average increase in the odds of adolescent mental illness as exposure to maternal distress increases.

These models were then adjusted for the described covariates (age, sex, SES, family functioning, single parent household and parental physical illness). In accordance with analyses procedures outlined by Statistics Canada and the 2014 OCHS Team, standardized weights were applied to make use of the complex sampling structure of the 2014 OCHS. This ensured that participants included in analyses were representative of the population of Ontario. Listwise deletion was utilized to manage missing data.

All analyses were performed using SPSS Statistics 23 (IBM SPSS Statistics) and were performed at the Statistics Canada Research Data Centre at McMaster University. To ensure that participant confidentiality was maintained, all observations were vetted by Statistics Canada personnel prior to release. In keeping with Statistics Canada policy, specific counts of both individual MINI-KID diagnoses, and sociodemographic variables could not be disclosed if fewer than 10 participants shared that characteristic.

Results

Table 1: Demographic characteristics of participants and their mothers

a P < 0.05 compared to group 1

b P < 0.05 compared to group 2

c P < 0.05 compared to group 3

d P < 0.05 compared to group 4

g, grams; K6, Kessler psychological distress scale; LIM, low income measure; SD, standard deviation

Table 1 contains the means of each characteristic and results of the pairwise analyses between the four comparison groups. No significant differences were observed for sex and participant age. Pairwise analyses for multiple comparisons revealed that significant differences existed for participant birth weight (group 2 vs 3), maternal age (groups 3 vs 4), K6 maternal distress scale (groups 2, 3 and 4), more than one health condition (groups 2, 3 and 4), single parent household (groups 3 and 4) and below the low income measure (groups 2, 3 and 4).

Table 2: Adjusted associations between increasing levels of maternal distress and odds of MINI-KID diagnoses (adolescent reported)

MINI-KID Diagnoses               Unadjusted OR (95% Cl)                     Adjusted OR (95%Cl)

Major Depressive Disorder                1.28 (1.02-1.61)    1.29 (1.01-1.67)

GAD     1.23 (1.02-1.48)    1.12 (0.91-1.39)

SAD     1.15 (0.77-1.70)    0.94 (0.61-1.45)

Social Anxiety    1.21 (0.89-1.63)    1.00 (0.71-1.40)

Specific Phobia   0.86 (0.60-1.16)    0.74 (0.54-1.02)

ADHD     1.45 (1.16-1.80)    1.30 (1.02-1.65)

Conduct     1.09 (0.71-1.69)    0.84 (0.53-1.33)

ODD     1.22 (0.97-1.53)    1.07 (0.84-1.37)

* Bolded values represent significant odds

Prior to statistical adjustment, the odds of major depressive disorder (MDD) (OR= 1.28 95% CI: 1.02-1.61), any subtype of ADHD (OR= 1.45 95% CI: 1.16-1.80), and generalized anxiety disorder (OR= 1.23 95% CI: 1.02-1.48) increased as exposure to level of maternal distress increased (none vs. prenatal vs. concurrent vs. prenatal+concurrent). There did not appear to be an increase is the odds of any other MINI-assessed diagnosis.

After adjusting for age, sex, SES, family functioning, single parent household and parental physical illness, each increase in level of maternal distress increased the odds of major depressive disorder (OR=1.29, 95% CI: 1.01- 1.67) and ADHD (OR=1.30, 95% CI: 1.02-1.65). The children of mothers with both prenatal and concurrent distress exhibited the highest odds of these disorders while those exposed to none had the lowest. These results are summarized in Table 2.

Statistically significant interactions after adjustment for covariates (maternal health, sex, age, SES, marital dysfunction and single motherhood) were noted between level of maternal distress and offspring major depressive disorder (P<.001), social anxiety (P=.028), specific phobia (P=.021), and generalized anxiety disorder (P=.001).

Table 3: Adjusted odds of the interaction between sex and maternal distress for the MINI-KID diagnoses (stratified results)

MINI-KID Diagnoses          Male adjusted OR (95%Cl)           Female adjusted OR (95%Cl)

Major Depressive Disorder              1.98 (1.37-2.86)           0.81 (0.55-1.19)

GAD                         1.63 (1.21-2.21)          0.78 (0.58-1.04)

Social Anxiety             2.02 (1.04-3.95)          0.75 (0.50-1.13)

Specific Phobia            1.06 (0.71-1.57)          0.50 (0.28-0.89)

* These models are adjusted for: maternal health, sex, age, SES, marital dysfunction and single motherhood

For each of the statistically significant interactions, associations between maternal distress and offspring psychopathology were examined in males and females separately. These analyses revealed that males were more susceptible to the effects of maternal distress for major depressiveepisodes(OR=1.98, 95% Cl: 1.37-2.86), social anxiety disorder (OR=2.02, 95% Cl: 1.04-3.95) and generalized anxiety disorder (OR=1.63, 95% Cl: 1.21-2.1). These results  suggest that increases in levels maternal distress amplified major depressive disorder, social anxiety and GAD risk in males. Interestingly, as levels of maternal distress increased, levels of specific phobia in females actually decreased(OR=0.50, 95% Cl: 0.28-0.89).

Discussion

This study aimed to explore the impact of exposure to maternal distress (prenatal, concurrent), as well as their joint effect on the mental health of their offspring in adolescence. After adjusting for covariates, we found that exposure to increasing levels of maternal distress increased the risk of major depressive disorder and ADHD in adolescence in a dose-dependent manner. We also observed that the impact of increasing maternal distress was amplified in male adolescents for major depressive disorder, social anxiety and GAD. Unexpectedly, females exposed to increasing levels of maternal distress actually had lower rates of specific phobia, though this was an isolated result.

Our findings of increasing risk for major depression and ADHD with exposure to elevated levels of maternal distress are consistent with the cumulative risk hypothesis. This hypothesis argues that the occurrence of multiple risks over time leads to a greater risk of psychopathology compared to single or more limited exposures to risk factors (Evans et al, 2013).

Prenatal maternal distress has been shown to have detrimental consequences on fetal development that may persist into infancy (Haselbeck et al, 2017), adolescence (Monk et al, 2013) and adulthood (Plant et al, 2016). During prenatal development the fetus is highly susceptible to a wide rage of stressors (e.g., maternal distress) that can adversely affect important biological pathways including the hypothalamus-pituitary- adrenal (HPA) axis (Weinstock, 2005; De Bruijn et al, 2009). The function of the HPA axis in pregnancy is complex (Ramborger, 2018), playing an integral role in stress response and vulnerability to mental and physical diseases later in life (Reynold, 2013). This is especially important because poor stress regulation is a common feature of emotional (e.g., depression) and behavioral problems (e.g., ADHD) in adolescence (Lupien, 2009). Therefore, an increased stress vulnerability due to maternal prenatal distress may have led in part to the increased risk of psychopathology later in life observed in this work (Buss et al., 2010; Pallarés & Antonelli, 2014).

Women who are distressed throughout their pregnancy are often also distressed after their pregnancy as well (Hippman et al, 2009). This ongoing maternal distress can affect the quality of the interaction between mothers and their offspring, including their adolescents (Yoo et al, 2014). Numerous studies have illustrated that mothers experiencing distress display more control over their adolescents (Benzies et al, 2015), exhibit less warmth (Karevold et al, 2017), and are less responsive during interactions with their child compared to non-depressed mothers (Foster et al, 2008). This can in turn affect the mother-adolescent relationship, and can result in poor adolescent adjustment (Martin et al, 2018). Moreover, distressed mothers tend to display poor modeling techniques, as they may expose their adolescent to depressive coping strategies and depression in the longer term (Flouri & Ioakeimidi, 2018). Therefore, the combination of altered biology emerging in response to prenatal distress, and later maternal distress and its impact on offspring may increase the risk of depression in adolescents.

While genetics play an important role in the pathophysiology of ADHD (Prince, 2008), prenatal factors have also been observed to influence its development (Sagiv et al, 2013). Indeed, a large number of studies have observed associations between prenatal maternal distress and the risk of problems like ADHD years later (Grizenko et al, 2012; Ronald et al, 2011). This has been hypothesized to be due to increased levels of maternal cortisol that may alter brain structures (e.g., amygdala) during fetal neurodevelopment (Davis et al, 2011). Maternal prenatal distress leads to the transfer of higher levels of maternal cortisol through the placenta, and lower levels of 11β-HSD_{2 ,} a placental enzyme responsible for converting cortisol into inactive cortisone (Painter et al, 2012). Other studies have found that maternal distress can activate the mother’s sympathetic nervous system, which then can reduce blood flow to the fetus by increasing resistance of the uterine artery (Teixeira et al, 1999). Such reductions may also negatively affect brain development (Dipietro, 2012) relevant to ADHD risk.

Studies have also shown that ADHD symptoms are highest in the children of women who experienced both prenatal and postnatal distress (Wolford et al, 2017). Moreover, concurrent maternal behaviour has also been linked to an increased risk of ADHD in children (Nelson et al, 2009). Links between maternal distress and parenting behaviours such as hostility (Verlaan et al, 2014), decreased affection and care (Silinskas et al, 2019), and overprotection (Fanti & Henrich, 2010) also predict ADHD in offspring (Gau and Chang, 2013).

Research on the interplay between prenatal distress and maternal distress in adolescence is quite limited. However, researchers have hypothesized that the interplay of distress at these two time periods impose greater risk than one time point alone (Kingston et al, 2015). Meaney (2001) reported that prenatal maternal distress alters the offspring’s HPA response to stress. Kozyrskyj and colleagues (2007) reported that poor mother-child interactions as a result of concurrent maternal distress result in epigenetic modifications of DNA, which increase the expression of glucocorticoid receptor genes and further alter the HPA response to stress in children. These findings suggest that the cumulative effect of prenatal and concurrent maternal distress amplify the risk of adolescent psychopathology by continuously limiting HPA functioning.

It is important to note however that we did not observe associations between maternal distress and an increased risk of problems related to anxiety or other forms of externalizing (i.e., ODD and conduct disorder) in adolescents. To date, the literature examining associations between maternal distress and later anxiety and externalizing problems has yielded inconsistent results (Dubois-Comtois et al, 2013). It is unclear why joint maternal distress lead to certain forms of psychopathology in our sample but not others. Further research is needed to differentiate the mechanisms by which maternal distress affects anxiety and externalizing problems.

This work also highlighted that adolescent males were more affected by increasing levels of maternal distress than females, particularly major depressive disorder, social anxiety and GAD. Studies suggest that the male embryo may be more vulnerable to prenatal stressors than females (Ellman et al, 2008), and so maternal distress may amplify risk in males because they are biologically more vulnerable (Sandman et al, 2013). Males may also be more affected by concurrent maternal distress. Indeed, Mirhosseini et al (2015) reported that males are affected more by postnatal maternal distress than girls, and that these effects can be long lasting. Moreover, males are more emotionally reactive and demand more attention from their mothers than do females (Kraemer, 2000), and mothers who are concurrently distressed are reported to be less responsive and affectionate towards their adolescents (Silinskas et al, 2019). This can establish an avoidant or disorganized form of attachment that may lead to more internalizing symptoms in adolescent males (Kerns & Brumariu, 2014).

It is unclear why maternal distress might be associated with a reduced risk of specific phobia in adolescent females. This result is consistent with the mismatch hypothesis of Nederhoff and Schmidt (2012) which posits that negative experiences early in life can better prepare individuals for later challenges. However, this is an isolated result and so requires replication in future studies.

It is important to view the results of this study in light of its limitations. First, maternal distress was assessed using self-report, and retrospectively for the prenatal period. While based on a validated question, it focused on more severe distress and involved only a single item. While this item increases the likelihood that distress would be reported validly (Lampea et al, 1999), it will have missed mothers who had milder distress. Another important limitation is that adolescent psychopathology could have contributed to concurrent maternal distress (Middeldorp et al, 2016) rather than maternal distress leading to offspring problems. While our finding of a dose-response association reduces this likelihood, it cannot be entirely ruled out. Thirdly, since data collection did not occur between the prenatal and concurrent distress period, it is unknown whether maternal distress continued or ceased and remerged during adolescence. This can affect the severity and chronicity of maternal distress and impact our results and their implications. Fourthly, our study only looked at a subset of the total MINI-KID sample, but the sample weights applied should ensure that the results are generalizable to the most populous province in Canada. Lastly, our study sample had access to universal healthcare and so this may limit the generalizability of the findings.

Despite these shortcomings, this study helps to fill a substantive gap in the literature by examining maternal distress and offspring psychopathology in adolescence. Most studies the impact of maternal distress focused on either prenatal or concurrent time periods independently, while our study examined both separately and jointly. Secondly, limited data are available regarding maternal distress and clinically significant adolescent mental disorders because most research has focused on infants and young children. To our knowledge, this study is the only one to use a structured diagnostic interview, a gold standard clinical assessment tool. Our study utilizes a large sample and applied sample weights to ensure the generalizability of our findings to the largest province in Canada.

The findings of this study suggest that the cumulative exposure to maternal distress increases the risk of clinically significant major depression disorder and ADHD on adolescent offspring. Further, we observed that the impact of increasing maternal distress was amplified in males for adolescent major depressive disorder, social anxiety and GAD. This work highlights the importance of identification and the continued monitoring and assessment of maternal mental health, followed by the application of appropriate interventions throughout childhood and adolescence to ensure the optimization of offspring mental health.

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