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Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic–pituitary–adrenal axis, the renin–angiotensin–aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient’s reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women’s health.

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section on “Special Populations” is the sixth of six guidelines articles. Results: Recent studies inform the treatment of MDD in children and adolescents, pregnant and breastfeeding women, women in perimenopause or menopause, and the elderly. Evidence for efficacy of treatments in these populations is more limited than for the general adult population, however, and risks of treatment in these groups are often poorly studied and reported. Conclusions: Despite the limited evidence base, extant data and clinical experience suggest that each of these special populations can benefit from the systematic application of treatment guidelines for treatment of MDD.

Data on the chronicity of mental disorder in children with chronic physical illness (CPI) are limited. We examined the prevalence and predictors of homotypic and heterotypic continuity of mental disorder in children with CPI. A sample of 263 children aged 2–16 years with physician-diagnosed CPI were recruited from outpatient clinics (e.g., dermatology, respiratory) at a Canadian pediatric academic hospital and followed for 24 months. Parent and child-reported mental disorders (mood, anxiety, behavioral, attention-deficit hyperactivity disorder [ADHD]) were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents at baseline, 6, 12, and 24 months. Marginal regression models were computed to identify clinical, parent, and demographic factors associated with mental comorbidity over time. Mental disorder was observed in 24–27% of children with CPI based on child reports and 35–39% based on parent reports. Parent-reported models revealed significant homotypic continuity for all mental disorders (ORs = 4.2–9.5), and heterotypic continuity between mood and anxiety disorders (OR = 2.2), ADHD and behavioral disorders (OR = 5.1), and behavioral and each mental disorder (ORs = 6.7–8.4). Child-reported models revealed significant homotypic continuity for mood (OR = 8.8) and anxiety disorder (OR = 6.0), and heterotypic continuity between anxiety and mood disorders (OR = 12.4). Child disability (ORs = 1.3–1.5) and parent psychopathology (ORs = 1.2–1.8) were the most consistent predictors of both child- and parent-reported mental disorder over time. Mental comorbidity was prevalent and persistent in children with CPI with homotypic and heterotypic continuity common across informants. Child disability and parent psychopathology may be priority targets within integrated family-centered models of care to prevent mental comorbidity in children with CPI.

IntroductionMultimorbidity, the co-occurrence of a chronic physical condition and mental disorder, affects a substantial number of children and youth and can lead to compromised quality of life, hardship for families, and an increased burden on the healthcare system. We are conducting a study to document the course of mental disorder in children and youth diagnosed with a chronic physical condition; identify predictors of child and youth multimorbidity; examine whether the effects of these predictors are moderated by relevant psychosocial and biological factors; explore potential inflammatory and stress biomarkers that mediate the onset of child and youth multimorbidity; and, assess whether multimorbidity in children and youth alters patterns of mental health service use.Methods and analysisMultimorbidity in Children and Youth Across the Life-course (MY LIFE) is a prospective study. Two hundred and fifty children and youth aged 2–16 years diagnosed with a chronic physical condition along with one parent will be recruited from the outpatient clinics at a paediatric tertiary care centre. Data will be collected using a multi-informant, multimethod design at four time-points (at recruitment, and at 6, 12 and 24 months postrecruitment). Parents will provide reports for all children/youth. In addition, youth ≥10 years will self-report. Mental disorder will be assessed using structured interviews. On completion of data collection, participant-reported data will be linked to provincial health records to identify mental health services use. Multilevel analyses (survival, proportional hazard, structural equation modelling) will be used to address MY LIFE objectives.Ethics and disseminationThis study has been approved by the University of Waterloo Human Research Ethics Board and the Hamilton Integrated Research Ethics Board. Findings will be disseminated to key stakeholders using a number of outlets (peer-reviewed publications and conferences, lay informational pamphlets, social media).

The prenatal environment can exert important effects on mental health. While much research has linked low birth weight to psychopathology, the intrauterine environment associated with high birth weight (macrosomia; > 4000 g) is also sub-optimal and may increase risk. Given the increasing prevalence of macrosomic births, understanding the mental health outcomes of infants born macrosomic can help refine theories of etiology, predict disorder, and target preventive interventions. Using data from the 2014 Ontario Child Health Study (OCHS), we examined the risk for psychiatric disorders in adolescents born macrosomic. Youth (N = 2151) aged 12–17 years completed the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Rates of common mental disorders assessed by the MINI-KID were compared between those born at normal birth weight (NBW; 2500–4000 g, n = 1817) and adolescents born macrosomic (> 4000 g, n = 334). These associations were then adjusted for participant age, sex, socioeconomic status (SES) of the family, parental mental health, and gestational diabetes mellitus. After adjustment for covariates, adolescents born macrosomic had higher odds of conduct disorder (CD; OR = 3.19, 95% CI: 1.37–7.43), oppositional defiant disorder (ODD; OR = 1.79, 95% CI: 1.11–2.91), and ADHD (OR = 1.77, 95% CI: 1.21–2.80). Moderation analyses revealed that males born macrosomic were more likely to have psychiatric problems than their female peers. Socioeconomic disadvantage also amplified the risk posed by macrosomia for ODD, ADHD, major depressive disorder, and generalized anxiety disorder. In this study, macrosomia was associated with an increased risk of clinically significant externalizing problems in adolescence, most notably among boys and those facing socioeconomic disadvantage.

During the COVID-19 pandemic, pregnant women have been at high risk for psychological distress. Lifestyle factors may be modifiable elements to help reduce and promote resilience to prenatal stress. We used Machine-Learning (ML) algorithms applied to questionnaire data obtained from an international cohort of 804 pregnant women to determine whether physical activity and diet were resilience factors against prenatal stress, and whether stress levels were in turn predictive of sleep classes. A support vector machine accurately classified perceived stress levels in pregnant women based on physical activity behaviours and dietary behaviours. In turn, we classified hours of sleep based on perceived stress levels. This research adds to a developing consensus concerning physical activity and diet, and the association with prenatal stress and sleep in pregnant women. Predictive modeling using ML approaches may be used as a screening tool and to promote positive health behaviours for pregnant women.

Objective: To determine if maternal pre-pregnancy body mass index (BMI) is associated with increased levels of internalizing and externalizing symptomatology in offspring throughout childhood and adolescence, and if these links persist after adjusting for the confounders of these associations. Method: We examined links between maternal pre-pregnancy BMI and internalizing and externalizing symptoms in the offspring of 2785 members of the Western Australian Pregnancy (Raine) Cohort. Mothers rated these problems using the Child Behavior Checklist when their children were 5, 8, 10, 14, and 17 years of age. Growth curves were generated using multilevel linear regression to examine associations and to determine if changes in levels of these symptoms varied overtime by maternal BMI. Results: Increased maternal pre-pregnancy BMI was associated with stably elevated levels of externalizing problems, and exhibited a statistically significant interaction with internalizing problems over time, indicating that youth born to mothers with higher maternal pre-pregnancy BMIs had less rapid decreases in internalizing scores as they got older. Significant positive associations between maternal pre-pregnancy BMI and elevated levels of internalizing problems emerged at age 8 and increased through 17. These findings persisted despite adjustment for confounders. Conclusions: Exposure to elevated maternal pre-pregnancy BMI is associated with increased levels of internalizing and externalizing problems throughout childhood and adolescence. Further work is required to establish if these associations are causal. If elevated maternal pre-pregnancy BMI is causally linked to psychopathology in offspring, it could provide a potentially realizable target for the prevention of mental health problems in youth.

Background Despite the high prevalence of mental health issues among young mothers, their subsequent needs for mental health care support does not correlate with their access and use of services. The purpose of this study, grounded in the experiences of young mothers living in Ontario, Canada, was to describe their experiences of using mental health services during the perinatal period, and to identify the attributes of services and professionals that influenced their decision to engage with mental health services. Methods As the qualitative component of a sequential explanatory mixed methods study, the principles of qualitative description informed sampling, data collection, and analysis decisions. In-depth, semi-structured interviews were conducted with a purposeful sample of 29 young mothers (≤ 21 years) who met diagnostic criteria for at least one psychiatric disorder, and who were ≥ 2 months postpartum. Interview data were triangulated with data from ecomaps and a sub-set of demographic data for this purposeful sample from the survey conducted in the quantitative study component. Qualitative data were analyzed using both conventional content analysis and reflexive thematic analysis; the subset of survey data extracted for these 29 participants were analyzed using descriptive statistics. Results Young mothers identified the need to have at least one individual, either an informal social support or formal service provider who they could talk to about their mental health. Among participants deciding to seek professional mental health support, their hesitancy to access services was grounded in past negative experiences or fears of being judged, being medicated, not being seen as an active partner in care decisions or experiencing increased child protection involvement. Participants identified organizational and provider attributes of those delivering mental health care that they perceived influenced their use of or engagement with services. Conclusion Organizations or health/social care professionals providing mental health services to young pregnant or parenting mothers are recommended to implement trauma-and violence-informed care. This approach prioritizes the emotional and physical safety of individuals within the care environment. Applying this lens in service delivery also aligns with the needs of young mothers, including that they are actively listened to, treated with respect, and genuinely engaged as active partners in making decisions about their care and treatment.

Maternal thyroid problems during pregnancy have been linked to neurocognitive impairments in children. While studies suggest that disorders of maternal thyroid function during pregnancy are associated with symptoms of mental health problems in children, little is known about the risk of clinically significant psychiatric disorders in adolescence. A sample of 2451 Canadian adolescents enrolled in the Ontario Child Health Study completed the Mini International Neuropsychiatric Interview for Children and Adolescents at 12–17 years of age. Their mothers self-reported thyroid problems during pregnancy. Gestational thyroid problems were associated with offspring oppositional defiant disorder (ODD; OR 3.73; 95% CI 1.69–8.24), conduct disorder (CD; OR 12.95; 95% CI 5.12–32.75), and social anxiety disorder (SAD; OR 6.25; 95% CI 2.53–15.47). Neither sex nor gestational age moderated associations between prenatal thyroid dysfunction and the majority of outcomes. School performance mediated 8% of the association between thyroid problems and SAD, 21% for CD and 53% for ODD.

Objective To identify converging themes from the neurodevelopmental hypothesis of schizophrenia and the pathophysiology of diabetic pregnancy and to examine mechanisms by which diabetes mellitus in a pregnant mother may increase the risk of schizophrenia in offspring. Methods We reviewed relevant publications on clinical, epidemiologic and animal studies of diabetic pregnancy and the neurodevelopmental aspects of schizophrenia. Results Epidemiologic studies have shown that the offspring of mothers who experienced diabetes mellitus during their pregnancies are 7 times more likely to develop schizophrenia, compared with those who were not exposed to diabetic pregnancy. Maternal hyperglycemia during pregnancy could predispose to schizophrenia in adult life through at least 3 prenatal mechanisms: hypoxia, oxidative stress and increased inflammation. Hyperglycemia increases oxidative stress, alters lipid metabolism, affects mitochondrial structure, causes derangements in neural cell processes and neuronal architecture and results in premature specialization before neural tube closure. The molecular mechanisms underlying these processes include the generation of excess oxyradicals and lipid peroxide intermediates as well as reductions in levels of polyunsaturated fatty acids that are known to cause increased dopaminergic and lowered γ-aminobutyric acidergic activity. The combination of hyperglycemia and hypoxia in pregnancy also leads to altered immune function including increased tumour necrosis factor-α, C-reactive protein and upregulation of other proinflammatory cytokines. Finally, maternal hyperglycemia could have a lasting impact on fetal cellular physiology, resulting in increased vulnerability to stress and predisposition to schizophrenia via a mechanism known as programming. These prenatal events can also result in obstetric complications such as fetal growth abnormalities and increased susceptibility to prenatal infection, all of which are associated with a spectrum of neurodevelopmental anomalies and an enhanced risk of schizophrenia. Conclusion On the basis of the evidence presented and taking into consideration the projected increases in the rates of diabetes mellitus among younger women of child-bearing potential, it is imperative that the neurodevelopmental sequelae of diabetic pregnancy in general, and the increased risk for schizophrenia in particular, receive further study.