Ryan J. Van Lieshout

A Review of Candidate Pathways Underlying the Association Between Asthma and Major Depressive Disorder

Objective: To consider the mechanisms that may link asthma and major depressive disorder (MDD). Asthma and MDD co-occur at higher rates than expected, but whether this reflects shared underlying pathophysiological mechanisms is not known. Methods: A review of the epidemiological data linking asthma and MDD was conducted and the possible biological mechanisms that could account for the high rate of this comorbidity were reviewed. Results: MDD occurs in almost half of patients with asthma assessed in tertiary care centers. Dysregulation of the hypothalamic pituitary adrenal axis may predispose people to both MDD and asthma, and similar alterations in the immune, autonomic nervous, and other key systems are apparent and may contribute to this increased risk of co-occurrence. Conclusions: High rates of MDD in asthma may result from the stress of chronic illness, the medications used to treat it, or a combination of the two. The high level of co-occurrence may also reflect dysregulation of certain stress-sensitive biological processes that contribute to the pathophysiology of both conditions. ANS = autonomic nervous system; CD4 = cluster of differentiation 4; COX = cyclooxygenase; COX-2 = cyclooxyenase-2; CRH = corticotrophin-releasing hormone; GC = glucocorticoid; GR = glucocorticoid receptor; HPA = hypothalamic pituitary adrenal; ICAM-1 = intracellular adhesion molecule-1; IDO = indoleamine-2,3-dioxygenase; IgE = immunoglobulin E; IL = interleukin; MDD = major depressive disorder; NFkB = nuclear factor kappa B; NKA = neuropeptides; NO = nitric oxide; PDE4 = phosphodiesterase-4; PG = prostaglandin; PGE2 = prostaglandin E2; Th2 = Type 2 T-helper cell; TNF = tumor necrosis factor.

Mental Health of Extremely Low Birth Weight Survivors in Their 30s

OBJECTIVE: To determine the risk for psychiatric disorders among extremely low birth weight (ELBW) survivors in their early to mid-30s and to determine whether those born small for gestational age or those exposed to a full course of antenatal corticosteroids (ACS) were at particularly high risk. METHODS: A prospective, longitudinal, population-based cohort of 84 ELBW survivors and 90 normal birth weight (NBW) control participants born in Ontario, Canada from 1977 to 1982 were assessed by interviewers naive to birth weight status using the Mini-International Neuropsychiatric Interview. RESULTS: ELBW survivors had lower odds of an alcohol or substance use disorder but higher odds of current non–substance-related psychiatric problems (odds ratio [OR] = 2.47; 95% confidence interval [CI], 1.19–5.14). Those born ELBW and SGA exhibited the same patterns with larger effects. ACS-exposed ELBW survivors had even higher odds of any current non–substance-related psychiatric disorder (OR = 4.41; 95% CI, 1.65–11.82), particularly generalized anxiety disorder (OR = 3.42; 95% CI, 1.06–11.06), the generalized type of social phobia (OR = 5.80; 95% CI, 1.20–27.99), and the inattentive subtype of attention-deficit/hyperactivity disorder (OR = 11.45; 95% CI, 2.06–63.50). CONCLUSIONS: In their early to mid-30s, ELBW survivors were less likely to have alcohol or substance use disorders but may be at greater risk for other psychiatric problems. Those exposed to ACS were at especially high risk and manifested no reduction in alcohol or substance use disorders. ELBW survivors exposed to ACS may be a special group at risk for psychopathology in adulthood.

Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition

BACKGROUND There is evidence to suggest an association between prenatal maternal stress and the development of asthma or other atopic diseases in offspring. Yet, insights on the lasting effect of multiple, common prenatal stressors are rare, and the effects of prenatal timing are poorly understood. Further, it remains elusive if prenatal life events modify the risk for atopic diseases in the context of a parental predisposition to atopy. OBJECTIVE We tested whether womens experiences of common, adverse life events during the first or second half of pregnancy predicted the risk of developing atopic diseases in their children and whether a reported parental atopic disease moderated this association. METHODS We calculated the odds of a child developing asthma, eczema, and/or allergic rhinitis at ages 6 or 14 years, depending on maternal prenatal exposure to negative life events in a sample of 1587 children from the Western Australian Pregnancy Cohort (Raine) Study by using multivariable logistic regression. RESULTS We observed that the likelihood of asthma and eczema at age 14 years was significantly increased in children of mothers who had experienced adverse life events during the second half of gestation (1 life event: adjusted odds ratio for asthma, 2.08 [95% CI, 1.22-3.54]). A stronger increase in the odds to develop asthma upon prenatal life events was present in children of mothers without asthma compared with mothers with asthma. CONCLUSIONS Maternal adverse life events during the second half of gestation are linked to an increased risk for the development of atopic disorders, asthma, and eczema, in the case of asthma, particularly in the absence of a maternal asthma.

Efficacy and acceptability of mood stabilisers in the treatment of acute bipolar depression: systematic review

BACKGROUND Although people with bipolar disorder spend more time in a depressed than manic state, little evidence is available to guide the treatment of acute bipolar depression. AIMS To compare the efficacy, acceptability and safety of mood stabiliser monotherapy with combination and antidepressant treatment in adults with acute bipolar depression. METHOD Systematic review and meta-analysis of randomised, double-blind controlled trials. RESULTS Eighteen studies with a total 4105 participants were analysed. Mood stabiliser monotherapy was associated with increased rates of response (relative risk (RR) = 1.30, 95% CI 1.16-1.44, number needed to treat (NNT) = 10, 95% CI 7-18) and remission (RR = 1.51, 95% CI 1.27-1.79, NNT = 8, 95% CI 5-14) relative to placebo. Combination therapy was not statistically superior to monotherapy. Weight gain, switching and suicide rates did not differ between groups. No differences were found between individual medications or drug classes for any outcome. CONCLUSIONS Mood stabilisers are moderately efficacious for acute bipolar depression. Extant studies are few and limited by high rates of discontinuation and short duration. Further study of existing and novel agents is required.

Role of maternal adiposity prior to and during pregnancy in cognitive and psychiatric problems in offspring

The purpose of this review is to summarize studies that have examined associations between maternal adiposity prior to and during pregnancy and cognitive and psychiatric problems in offspring. Of the 11 studies published since a 2011 systematic review, four examined cognitive outcomes alone, four assessed psychopathology exclusively, and three reported on both cognitive and psychiatric endpoints. Ten studies provided evidence of a link. These data suggest that the offspring of women who are overweight or obese during pregnancy are at increased risk for cognitive deficits, externalizing problems (particularly attention-deficit/hyperactivity disorder), and internalizing psychopathology in childhood and adolescence; however, the effect sizes were small to medium and a definitive causal association remains to be proven.

Birth Weight, Stress, and Symptoms of Depression in Adolescence: Evidence of Fetal Programming in a National Canadian Cohort

Objective: To investigate evidence of fetal programming in humans by studying whether adolescents born at high or low birth weights (LBW) are more likely to experience symptoms of depression and anxiety after experiencing stress. Method: The sample included 3732 members of a prospective Canadian cohort study assessed for symptoms of depression and anxiety at age 12 to 15 years (2006/2007), and had birth weight and gestational age (GA) data recorded in 1994/1995. Major stressful life events and chronic stressors were also reported throughout childhood. Results: After adjusting for acute and chronic stress, being born small for GA (SGA) (OR 1.50; 95% CI 1.08 to 2.08) or large (OR 1.31; 95% CI 0.99 to 1.72) for GA was associated with an increased risk of depression and anxiety in adolescence, compared with adolescents who were born at a weight appropriate for their GA. Most interactions between birth weight and stress were not significant; however, the relation between chronic stress and adolescent depression and anxiety was more pronounced in males who were born SGA (interaction P < 0.05). Conclusions: The link between birth weight and depression is complex and evidence of fetal programming is inconsistent; however, people born at LBW may be at an increased risk of depression in the face of chronic stress.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 6. Special populations: Youth, women, and the elderly

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.

Health, Wealth, Social Integration, and Sexuality of Extremely Low-Birth-Weight Prematurely Born Adults in the Fourth Decade of Life

IMPORTANCE Although it has been previously reported that the transition of extremely low-birth-weight survivors (≤1000 g) in their mid-20s was similar to that of normal-birth-weight controls (>2500g), there was uncertainty as to whether this positive pattern would persist. OBJECTIVE To compare the social functioning of low-birth-weight prematurely born adults aged 29 to 36 years with that of normal-birth-weight term controls. DESIGN, SETTING, AND PARTICIPANTS A population-based longitudinal cohort study was conducted in Ontario, Canada, between March 14, 2011, and August 13, 2013, among 100 of 165 low-birth-weight survivors (60.6%) prematurely born between January 1, 1977, and December 31, 1982, and 89 of 144 sociodemographically matched normal-birth-weight term controls (61.8%) recruited at age 8 years. Neurologic impairments were present in 20 premature participants (20.0%). EXPOSURES Extremely low birth weight. MAIN OUTCOMES AND MEASURES Information on health, educational level, employment, social integration, sexuality, and reproduction was obtained through standardized questionnaires completed by the participants. RESULTS Participants included 100 (39 males) extremely low-birth-weight survivors and 89 (33 males) normal-birth-weight term controls. The groups did not differ in the highest educational level achieved or in family and partner relationships. However, a lower proportion of premature adults was employed (odds ratio [OR], 0.37; 95% CI, 0.15 to 0.93) and fewer were employed full time (OR, 0.49; 95% CI, 0.24 to 0.98). The premature group had a mean total personal income of

Mental Health of Extremely Low Birth Weight Survivors: A Systematic Review and Meta-Analysis.

20 000 less than controls, and more required social assistance (OR, 4.16; 95% CI, 1.13 to 15.33). Compared with the control group, more members of the premature group remained single (OR, 1.95; 95% CI, 1.08 to 3.50), had never had sexual intercourse (OR, 11.30; 95% CI, 2.56 to 49.91), did not have children (OR, 0.52; 95% CI, 0.27 to 0.99), reported more chronic health conditions (β, 1.54; 95% CI, 0.79 to 2.30), had lower self-esteem (β, 8.40; 95% CI, 1.68 to 15.12), and were less likely to have current drug abuse or dependence (OR, 0.29; 95% CI, 0.90 to 0.92) or lifetime alcohol abuse or dependence (OR, 0.30; 95% CI, 0.15 to 0.59). A higher proportion of premature adults without neurosensory impairments identified themselves as nonheterosexual (OR, 4.87; 95% CI, 1.01 to 23.69). After exclusion of individuals with neurosensory impairments, differences in employment, social assistance, marital status, and reproduction were no longer significant. CONCLUSIONS AND RELEVANCE In the fourth decade of life, extremely low-birth-weight survivors achieved similar educational levels and family and partner relationships, and reported fewer risky behaviors compared with controls. However, they had lower levels of employment, income, and self-esteem, and fewer were married and had children. It is therefore essential that these individuals receive necessary support and continued monitoring throughout life.

Relations between Asthma and Psychological Distress: An Old Idea Revisited

Although individuals born at extremely low birth weight (ELBW; < 1,000 g) are the most vulnerable of all preterm survivors, their risk for mental health problems across the life span has not been systematically reviewed. The primary objective of this systematic review and meta-analysis was to ascertain whether the risk for mental health problems is greater for ELBW survivors than their normal birth weight (NBW) peers in childhood, adolescence, and adulthood. Forty-one studies assessing 2,712 ELBW children, adolescents, and adults and 11,127 NBW controls were reviewed. Group differences in mental health outcomes were assessed using random effects meta-analyses. The impacts of birthplace, birth era, and neurosensory impairment on mental health outcomes were assessed in subgroup analyses. Children born at ELBW were reported by parents and teachers to be at significantly greater risk than NBW controls for inattention and hyperactivity, internalizing, and externalizing symptoms. ELBW children were also at greater risk for conduct and oppositional disorders, autistic symptoms, and social difficulties. Risks for parent-reported inattention and hyperactivity, internalizing, and social problems were greater in adolescents born at ELBW. In contrast, ELBW teens self-reported lower inattention, hyperactivity, and oppositional behavior levels than their NBW peers. Depression, anxiety, and social difficulties were elevated in ELBW survivors in adulthood. Group differences were robust to region of birth, era of birth, and the presence of neurosensory impairments. The complex needs faced by children born at ELBW continue throughout development, with long-term consequences for psychological and social well-being.