Adolescent mental health—Opportunity and obligation

Lee, Francis S.; Heimer, Hakon; Giedd, Jay N.; Lein, Edward S.; Šestan, Nenad; Weinberger, Daniel R.; Casey, B. J.

doi:10.1126/science.1260497

Cited by 432 publications

(329 citation statements)

References 16 publications

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“…Parallel to efforts to improve adolescent mental health (Lee et al, 2014), we advocate for new avenues in dementia research that bridge discoveries in biomedical and social sciences and use the potential of social health to guide novel interventions. We propose social health serves as a new paradigm in dementia research.…”

Section: Social Health and Dementia Researchmentioning

confidence: 99%

Social health and dementia: the power of human capabilities

Vernooij‐Dassen

Jeon

2016

Int. Psychogeriatr.

100

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Section: Social Health and Dementia Researchmentioning

confidence: 99%

Social health and dementia: the power of human capabilities

Vernooij‐Dassen

Jeon

2016

Int. Psychogeriatr.

100

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“…

Most common mental disorders appear before adulthood [1]. Therefore, the ability to identify at-risk children is essential for the design and delivery of prevention programs.

…”

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confidence: 99%

Towards understanding and acting on risk factors for developmental psychopathology

Moreno

2018

Eur Child Adolesc Psychiatry

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Most common mental disorders appear before adulthood [1]. Therefore, the ability to identify at-risk children is essential for the design and delivery of prevention programs. Emotional and behavioural dysregulation are key symptomatic expressions of vulnerability in children and important predictors of a broad range of mental outcomes during late adolescence and adult life [2]. The exploration of risk factors leading to this vulnerability represents an important area of research in child psychiatry. This issue of European Child and Adolescent Psychiatry (ECAP) includes several articles focusing on predictive factors for emotional and behavioural dysregulation in childhood or adolescence.In one study, researchers analysed perceived parenting style, as measured by the Parental Bonding Inventory (PBI), as a potential factor modulating psychopathological outcomes in a school-based population of more than a thousand subjects [3]. The cohort was evaluated for emotional and behavioural difficulties at ages 7-9, and again 9 years later, at a mean age of 18 years. The authors found a high correlation between childhood emotional and behavioural traits and adolescent outcomes. They also found that perceived adequate maternal and paternal care had positive effects on socio-emotional development. Positive parent-child relationships had been regarded previously as enhancing resilience towards negative emotional and behavioural outcomes even in the presence of other environmental [4] or genetic risks [5]. However, in the present work, although optimal parenting of both parents was necessary for satisfactory emotional development, the authors found a differential effect. For participants who already displayed behavioural dysregulation during childhood, optimal care by the father, but not by the mother, lowered the risk of developing behavioural problems from pre-puberty to adolescence. This suggests that highly reactive children are especially sensitive to positive paternal care.This ECAP issue also examines the biological underpinnings of emotional dysregulation. For example, van der Knaap et al. used functional MRI to study amygdala responses to negative emotional faces in children aged 6-9 years in the Generation R Study, a population-based sample [6]. They classified children by the presence of maternal depressive symptoms during pregnancy. Those with clinically relevant maternal depressive symptoms presented with increased amygdala hyper-responsivity, indicating neural processing different from that in control children. The findings do not establish the causality of psychopathology at the time of evaluation (6-9 years). In fact, the different groups were not significantly different in their frequency of internalizing or externalizing problems. However, most psychiatric disorders, including affective disorders, typically appear later in life, rendering the use of psychopathology to differentiate the two groups early on as problematic. Instead, the authors suggest that amygdala hyper-responsivity in children may be explored ...

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“…The developmental phase of adolescence is characterized by dynamic changes in gene expression, frontolimbic circuitry (3,4), and overall tone of the endocannabinoid system, which are implicated in anxiety (5)(6)(7).…”

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confidence: 99%

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species

Gee

Fetcho

Jing

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3-to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxietyrelated behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.A nxiety disorders typically emerge during adolescence, when the incidence of mental illness peaks (1, 2). The developmental phase of adolescence is characterized by dynamic changes in gene expression, frontolimbic circuitry (3, 4), and overall tone of the endocannabinoid system, which are implicated in anxiety (5-7).The corticolimbic endocannabinoid system undergoes dynamic changes across development. The onset of adolescence is marked by the highest expression of type 1 cannabinoid receptor (CB1) in both cortical and subcortical brain regions, with CB1 expression declining to adult levels throughout adolescence (8, 9). Across the amygdala and prefrontal cortex, fatty acid amide hydrolase (FAAH) expression shows a transient increase from postnatal day 35 (P35) to P45 during adolescence in mice (10). Consistent with the regulatory role of FAAH, anandamide (AEA) levels show an inverse pattern of a peak at P35 and subsequent decrease during adolescence (10, 11). AEA is an endogenous ligand for the CB1 receptor, suggesting that the concurrent changes in AEA and CB1 expression reflect decreasing endocannabinoid signaling during adolescence (12), which may be associated with increasing risk for anxiety (Fig. 1).A common human polymorphism in the gene encoding FAAH (C385A; rs324420), the primary catabolic enzyme of the prototypical endocannabinoid AEA, regulates FAAH activity. The variant FAAH A385 allele destabilizes the FAAH protein, causing lower levels of FAAH enzymatic activity and/or increased levels of AEA in T lymphocytes and brain (13,14). Phenotypic expression of common polymorphism...

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Adolescent mental health—Opportunity and obligation

Abstract: Emerging neuroscience offers hope for treatments

Cited by 432 publications

References 16 publications

Social health and dementia: the power of human capabilities

Social health and dementia: the power of human capabilities

Towards understanding and acting on risk factors for developmental psychopathology

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species

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