Michelle L. Byrne

So depression is an inflammatory disease, but where does the inflammation come from?

BackgroundWe now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’DiscussionThis review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.SummaryThe identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

Pilot study of a mindfulness‐based, multi‐component, in‐school group sleep intervention in adolescent girls

Existing literature links poor sleep and anxiety symptoms in adolescents. This pilot study aimed to develop a practical method through which a program to improve sleep could reach adolescents in need and to examine the feasibility of a mindfulness‐based, multi‐component group sleep intervention using sleep and anxiety as outcome measures.

Acute phase protein and cytokine levels in serum and saliva: A comparison of detectable levels and correlations in a depressed and healthy adolescent sample

Recent research has examined associations between inflammation and mental health, and has increasingly focused on utilising younger samples to characterise the temporal relationship between inflammatory responses and the emergence of other symptoms. These studies have typically used blood to measure inflammation, although rates of detection for many inflammatory markers appear to be low. Saliva is a safe and low-cost alternative, and adult research has shown that levels of some salivary markers correlate well with those in serum. However, no research has examined this association in young people. This study examined 16 inflammatory markers in serum and saliva in 17 depressed adolescents and 18 healthy controls, aged 13-18 years. In general, detection rates were higher in saliva compared to in serum. When non-detectable levels were excluded, serum levels of C-reactive protein (CRP) correlated with salivary CRP (r=0.424, p=0.015), and this correlation appeared to only exist for those individuals with high levels of serum CRP (r=0.599, p=0.014). However, when non-detectable levels were included as zero, salivary levels of CRP, interleukin (IL)-2, IL-12p70, and interferon (IFN)-γ correlated with their serum counterparts. No significant clinical group differences in any acute phase proteins or cytokines were present. This study suggests that saliva can be used to measure inflammation in studies with adolescent participants, especially CRP, as it appears to correlate with systemic inflammation for those individuals who are expected to have high levels of inflammation. Implications for future directions in research on salivary inflammatory markers are discussed.

The lifetime experience of traumatic events is associated with hair cortisol concentrations in community-based children

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal axis (HPAA) and increase risk for negative health outcomes. Recent research suggests that cortisol in scalp hair represents a promising measure of HPAA function. However, little is known about the relationship between early exposure to traumatic events and hair cortisol concentrations (HCC) in childhood, a critical period of HPAA development. The current study measured HCC in scalp hair samples collected from 70 community-based children (14 males, mean age=9.50) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study (iCATS). Data were also collected on lifetime exposure to traumatic events and current depressive symptoms. Lifetime exposure to trauma was associated with elevated HCC; however, HCC was not associated with current depressive symptoms. Consistent with some prior work, males were found to have higher HCC than females, although results should be treated with caution due to the small number of males who took part. Our findings suggest that hair cortisol may represent a biomarker of exposure to trauma in this age group; however, further study is necessary with a particular focus on the characterization of trauma and other forms of adversity.

Parenting During Early Adolescence and Adolescent-Onset Major Depression A 6-Year Prospective Longitudinal Study

In this study, we investigated the prospective relationship between maternal behaviors observed during mother-adolescent interactions and the onset of major depressive disorder (MDD) between early and late adolescence (ages 12–18). Maternal expressions of emotion and maternal responses to their child’s expressions of emotion were both examined. Results demonstrated that higher rates of maternal aggressive behavior and lower rates of maternal positive behavior prospectively predicted MDD onset across adolescence. In addition, negative (i.e., aggressive and dysphoric) maternal responses to adolescents’ aggressive and positive behaviors predicted MDD onset. Maternal dysphoric behavior and the way mothers respond to adolescents’ dysphoria were not related to MDD onset. These results extend previous findings on the relationship between parenting behaviors and depression onset in early to midadolescence and suggest that maternal emotion socialization behaviors in early adolescence prospectively predict MDD onset across the entire course of adolescence.

AUTONOMIC CARDIAC CONTROL IN DEPRESSED ADOLESCENTS

Background: The aim of this study was to identify the aspects of cardiac physiology associated with depressive disorder early in life by examining measures of autonomic cardiac control in a community‐based sample of depressed adolescents at an early phase of illness, and matched on a number of demographic factors with a nondepressed comparison group. Methods: Participants were 127 adolescents (44 boys), ages 14–18, who formed two demographically matched groups of clinically depressed and nondepressed participants. Adolescents were excluded if they evidenced comorbid externalizing or substance‐dependence disorders, were taking medications with known cardiac effects, or reported regular nicotine use. Resting measures of heart rate, respiratory sinus arrhythmia, skin conductance level, blood pressure, and pre‐ejection period were collected. Results: Depressed adolescents had resting heart rates significantly higher than those of healthy adolescents. No other measure of autonomic functioning differentiated the groups. Post hoc analyses were conducted to examine the influence of illness chronicity, severity, comorbidity, and sex on cardiac psychophysiology. These variables did not appear to exert a significant influence on the findings. Conclusions: Our findings suggest that neither autonomic cardiac control, illness chronicity, or severity, nor medication effects fully explain resting heart rate differences between depressed and nondepressed adolescents. Future research on depression and heart rate should consider mechanisms other than sympathetic or parasympathetic control as potential explanations of heart rate differences, including blood‐clotting mechanisms, vascular and endothelial dysfunction of the coronary arteries, and inflammatory immune system response. Depression and Anxiety, 2010.

Maternal Parenting Behaviors and Adolescent Depression: The Mediating Role of Rumination

Substantial evidence suggests that rumination is an important vulnerability factor for adolescent depression. Despite this, few studies have examined environmental risk factors that might lead to rumination and, subsequently, depression in adolescence. This study examined the hypothesis that an adverse family environment is a risk factor for rumination, such that the tendency to ruminate mediates the longitudinal association between a negative family environment and adolescent depressive symptoms. It also investigated adolescent gender as a moderator of the relationship between family environment and adolescent rumination. Participants were 163 mother–adolescent dyads. Adolescents provided self-reports of depressive symptoms and rumination across three waves of data collection (approximately at ages 12, 15, and 17 years). Family environment was measured via observational assessment of the frequency of positive and aggressive parenting behaviors during laboratory-based interactions completed by mother-adolescent dyads, collected during the first wave. A bootstrap analysis revealed a significant indirect effect of low levels of positive maternal behavior on adolescent depressive symptoms via adolescent rumination, suggesting that rumination might mediate the relationship between low levels of positive maternal behavior and depressive symptoms for girls. This study highlights the importance of positive parenting behaviors as a possible protective factor against the development of adolescent rumination and, subsequently, depressive symptoms. One effective preventive approach to improving adolescent mental health may be providing parents with psychoeducation concerning the importance of pleasant and affirming interactions with their children.

Pituitary volume mediates the relationship between pubertal timing and depressive symptoms during adolescence

Early timing of puberty (i.e., advanced pubertal maturation relative to peers) has been linked to the onset of depressive symptoms during the early adolescent phase. However, the precise neurobiological mechanisms linking early pubertal timing to adolescent depressive symptoms are not clear. We investigated whether the volume of the pituitary gland, a key component of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, mediated the relationship between pubertal timing and depressive symptoms in 155 adolescents (72 females) both cross-sectionally and longitudinally. At baseline (M age 12.7, SD 0.5 years), early pubertal timing predicted larger pituitary gland volume and higher depressive symptoms (especially for girls), but there was no mediation effect. Longitudinally, however, larger pituitary gland volume at baseline was found to mediate the relationship between early pubertal timing and increased depressive symptoms over time (M follow-up period=2.57 years, SD=0.26) for both boys and girls. Our findings suggest that neurobiological mechanisms are partly responsible for the link between early pubertal timing and depressive symptoms in adolescents. We speculate that an enlarged pituitary gland in adolescents with early pubertal timing might be associated with hyperactivation of the hormonal stress response, leading to increased susceptibility to environmental stressors, and subsequent development of depressive symptoms. Given the well-established relationship between increasing depressive symptoms in adolescence and later disorder, these findings have implications for targeted prevention and early intervention strategies for depressive disorders in adolescence.

A systematic review of adrenarche as a sensitive period in neurobiological development and mental health

Substantial hormonal and neurobiological changes occur during puberty, and are widely argued to render this period of life a sensitive period in terms of risk for mental health problems. However, there is a paucity of research focusing on adrenarche, the earlier phase of pubertal development. Furthermore, there is a limited understanding of the association between adrenarche and neural development during this phase of life. We systematically reviewed research examining human adrenarcheal development as operationalized by hormonal levels of DHEA and DHEA-S, in relation to indices of mental health (Systematic Review 1). We then reviewed the limited amount of literature that has examined the association between adrenarcheal development and brain structure or function (Systematic Review 2). In general, studies showed that earlier timing of adrenarche was associated with greater mental health symptoms, and there is emerging support that brain development plays a role in this relationship. However, several methodological inconsistencies were noted. We propose that future research in this area test a theoretical model of adrenarche as a sensitive period of neurobiological development, whereby timing of exposure to hormones interacts with brain development, biological sex, and psychosocial stress to influence environmental sensitivity and risk for mental health problems through adolescence.

Associations between early adrenarche, affective brain function and mental health in children

Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology.