Nonsuicidal Self-Injury in Adolescent and Emerging Adult Childhood Cancer Survivors: A First Exploration.

Purpose: This study examines nonsuicidal self-injury (NSSI) in adolescent and emerging adult survivors of childhood cancer, aiming to gain a first understanding of the phenomenon, its relation to general and cancer-specific functioning, and the stability of NSSI engagement over time. Methods: Dutch-speaking survivors (n = 125, age range = 14-25 years) participated in the first three annual waves of the Longitudinal Identity Study of Childhood Cancer Survivors study. Descriptive characteristics of lifetime NSSI were calculated. Multivariate analysis of variance (MANOVA) and χ2-analyses were performed to examine differences in demographic and clinical characteristics between survivors with and without lifetime NSSI. To assess differences in general and cancer-specific functioning between survivors with and without lifetime NSSI, two MANOVA analyses were performed. Finally, prevalence rates of current NSSI across the three waves were calculated, followed by χ2-analyses to explore differences in current NSSI over time. Results: The prevalence and characteristics of lifetime NSSI engagement resembled those in the general population. Although demographic and clinical characteristics were unrelated to NSSI engagement, several meaningful differences were found in both general and cancer-specific functioning between survivors with and without NSSI. Survivors with lifetime NSSI experienced more depressive symptoms and difficulties with identity formation (i.e., lower levels of identity synthesis and higher levels of identity confusion). In addition, they experienced more post-traumatic stress symptoms and cancer-related worries, and identified less as a "cancer patient." Conclusions: This study provides a first understanding of NSSI engagement in survivors of childhood cancer, mapping the characteristics of NSSI and its associations with both general and cancer-specific functioning.

Mental health clinical pathways for children and young people with long-term health conditions: A systematic review.

RATIONALE: Clinical pathways (CPWs) are structured care plans that set out essential steps in the care of patients with a specific clinical problem. Amidst calls for the prioritisation of integrated mental and physical health care for young people, multidisciplinary CPWs have been proposed as a step towards closer integration. There is very limited evidence around CPWs for young people with mental and physical health needs, necessitating a review of the literature. AIMS AND OBJECTIVES: The aim of this review is to understand how clinical pathways have been used to deliver mental health support to children and young people with long-term physical health conditions and their effectiveness across a range of outcomes. METHODS: The databases MEDLINE, CENTRAL, PsycINFO and CINAHL were searched from inception to 6 September 2023. Keywords linked to children and young people, mental health, long-term physical health conditions and CPWs were used. Studies using either quantitative or qualitative research designs were included. All studies must have evaluated a CPW to provide mental health support to children and young people (up to 25 years old) with long-term health physical conditions. Both mental and physical health outcomes were considered. Pathways were grouped by integration 'model' as described in the wider literature. RESULTS: The initial search returned 4082 studies after deduplication. A total of eight studies detailing six distinct care pathways (232 participants [170 children and young people; 50 caregivers; 12 healthcare professionals]) met eligibility criteria and were included in the analysis. Four pathways were conducted within an 'integrated model'; two were a combination of 'integrated' and 'colocated'; and none within a 'co-ordinated model'. Only pathways within an integrated model reported quantitative health outcomes, with improvements across a range of mental health measures. One negative physical health outcome was reported from an integrated diabetes pathway, but this should be interpreted with caution. CONCLUSION: This review identified a range of CPW designs but most fell under an integrated model. The results suggest that calls for integrated mental health pathways in this population may be appropriate; however, conclusions are limited by a paucity of evidence.

Reward positivity moderates the association between pubertal status and social anxiety symptoms in nine-to-12-year-old youths.

The transition to adolescence is characterized by rapid development of puberty, reward processing, and internalizing psychopathology (i.e., depression and anxiety). More advanced pubertal status and altered reward processing are both known to be associated with elevated internalizing symptoms. However, it was unclear to what extent pubertal status and reward processing interacted with each other in predicting internalizing psychopathology. We examined how the puberty-psychopathology association was moderated by the reward processing indexed by ERPs, including the reward positivity (RewP) and the late positive potential (LPP). A-hundred-and-fifteen nine-to-12-year-old typically developing youths (66 girls; Mean age/SD =10.98/1.18 years) reported their pubertal status and symptoms of depression and social anxiety and completed an EEG Doors task that assessed monetary reward feedback processing. A principal component analysis of the ERP data identified a RewP, an anterior LPP, and a posterior LPP, elicited by the win and loss feedback of the task. The puberty-social anxiety relationship was moderated by the RewP, an identified neural marker of reward sensitivity. Specifically, more advanced puberty was associated with heightened social anxiety symptoms in the presence of a larger, but not smaller, RewP. We did not observe any moderating effect of the LPPs. Our study provided novel evidence that a hypersensitivity toward the reward stimuli (indexed by an enlarged RewP) further exacerbated the risks associated with more advanced pubertal status for social anxiety.

Hypersensitivity of the nicotinic acetylcholine receptor subunit (CHRNA2L9'S/L9'S) in female adolescent mice produces deficits in nicotine-induced facilitation of hippocampal-dependent learning and memory.

Adolescence is characterized by a critical period of maturation and growth, during which regions of the brain are vulnerable to long-lasting cognitive disturbances. Adolescent exposure to nicotine can lead to deleterious neurological and psychological outcomes. Moreover, the nicotinic acetylcholine receptor (nAChR) has been shown to play a functionally distinct role in the development of the adolescent brain. CHRNA2 encodes for the α2 subunit of nicotinic acetylcholine receptors associated with CA1 oriens lacunosum moleculare GABAergic interneurons and is associated with learning and memory. Previously, we found that adolescent male hypersensitive CHRNA2L9'S/L9' mice had impairments in learning and memory during a pre-exposure-dependent contextual fear conditioning task that could be rescued by low-dose nicotine exposure. In this study, we assessed learning and memory in female adolescent hypersensitive CHRNA2L9'S/L9' mice exposed to saline or a subthreshold dose of nicotine using a hippocampus-dependent task of pre-exposure-dependent contextual fear conditioning. We found that nicotine-treated wild-type female mice had significantly greater improvements in learning and memory than both saline-treated wild-type mice and nicotine-treated CHRNA2L9'S/L9' female mice. Thus, hyperexcitability of CHRNA2 in female adolescent mice ablated the nicotine-mediated potentiation of learning and memory seen in wild-types. Our results indicate that nicotine exposure during adolescence mediates sexually dimorphic patterns of learning and memory, with wild-type female adolescents being more susceptible to the effects of sub-threshold nicotine exposure. To understand the mechanism underlying sexually dimorphic behavior between hyperexcitable CHRNA2 mice, it is critical that further research be conducted.

Study on Awareness of Suicide and Suicide Prevention Among Community Youth.

Objectives: South Korea has the highest suicide rate among Organisation for Economic Co-operation and Development countries; there is an increasing trend in suicide attempts among middle and high school students. Various factors contribute to the risk of suicide among adolescents, and the perception of suicide prevention has emerged as a significant factor. This study aimed to investigate the association between emotional and behavioral difficulties among middle and high school students and their perceptions of suicide prevention and to explore differences in suicide perception according to age. Methods: A survey was conducted among community middle and high school students, including 530 participants, between 2020 and 2021. Emotional and behavioral difficulties were assessed using the Strengths and Difficulties Questionnaire-Korean version, and participants were asked to complete a questionnaire on the importance and possibility of suicide prevention. A correlation test and analysis of variance were used to examine the relationships between the variables, and suicide awareness was compared according to age. Results: The participants who displayed higher strength or lower difficulty were more likely to respond positively to suicide prevention measures. They also exhibited high strength and low difficulty levels, thus agreeing with the importance of suicide prevention. Regarding age-related perceptions of suicide, adults aged 20-29 years reported the lowest probability of suicide prevention. Conclusion: Suicide perceptions influence the incidence of suicide. Therefore, active societal engagement through suicide prevention campaigns and related education is essential to improve such perceptions. Continuous attention and support are required to address this issue.

Famine exposure in early life increases risk of cataracts in elderly stage.

Background: Epidemiological studies have shown that early-life nutritional deficiencies are associated with an increased risk of diseases later in life. This study aimed to explore the correlation between famine exposure during the early stages of life and cataracts. Methods: We included 5,931 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 cross-sectional data in our study. Subjects were categorized into three groups by their age during the famine: adulthood group, school age famine exposure group, and teenage famine exposure group. Utilizing binary logistic regression models, we investigated the relationship between early-life famine exposure and cataracts. Results: Compared to the adulthood group, both the school age exposure group (OR = 2.49, 95%CI = 1.89-3.27) and teenage exposure group (OR = 1.45, 95%CI = 1.20-1.76) had a heightened risk of developing cataracts in elderly stage. And the sex differences in the impact of famine during early years on elderly cataract risk were observed, particularly indicating a higher risk among women who experienced childhood famine compared to men with similar exposure. Conclusion: Famine exposure during the early stages of life is associated with a heightened risk of developing cataracts in old age. To prevent cataracts in elderly individuals, particularly in females, measures should be taken to address nutritional deficiencies in these specific periods.

The factors associated with the knowledge of brushing teeth with fluoridated toothpaste among high school students in Al-Madinah, Saudi Arabia.

Objective: The use of fluoridated toothpaste (FT) is essential for controlling caries. This analytical cross-sectional study aimed to determine the proportion of students who brushed their teeth with fluoridated toothpaste/or do not know the content at least once a day and to determine the factors associated with the knowledge of brushing teeth with FT. Methods: An anonymous questionnaire was distributed during the academic year 2019-2020 among 439 high school students. The data collected included sociodemographic characteristics and oral-health-related variables [e.g., brushing teeth, knowledge of the effect of fluoride on caries (KEFC) and dental service utilisation (DSU)]. The dependent variable was the knowledge of using FT when brushing teeth (Yes or do not know). Descriptive, bivariate, and logistic regression analysis were performed. Results: The response rate was 98% (n = 432) and usable data was 88% (n = 385). The median (IQR) age of the students was 16.00 (1) years, and 190 (47%) were males. Eighty eight percent of the students brushed their teeth with toothpaste daily with no knowledge of toothpaste content and only 86 (21.8%) knew the content of the toothpaste used for brushing their teeth i.e., FT. The multivariable analyses revealed an association of family income and KEFC with brushing teeth with FT [adjusted odds ratio (AOR): 1.98, 95% confidence interval (CI): 1.14-3.43, p = 0.015 and AOR = 6.11, 95% CI: 3.45-10.83, p < 0.001, respectively]. Conclusions: While the brushing and use of toothpaste among high school students was common, the knowledge of the content of toothpaste used for brushing teeth was less common and was associated with family income and KEFC.

Irritability: associations with real-time affect dynamics, social interactions, and daily substance use in older adolescents.

Irritability is a common and clinically significant symptom associated with a wide range of negative outcomes. Ecological Momentary Assessment (EMA) is a valuable tool for capturing experiences, such as emotions, social interactions, and substance use in real-time, and may be useful in understanding how irritability is related to everyday functioning. We investigated cross-sectional associations between a widely used self-report irritability rating scale and affect dynamics, social interactions, and substance use captured with EMA (5 surveys daily for 14 days) in 349 18-year-olds. We also examined the associations of self- and parent-reported irritability at ages 12 and 15 with the age 18 EMA variables to explore whether these relationships persist over time. Youth-reported irritability at age 18 was linked to greater intensity, variability, and inertia of irritability, sadness, and anxiety, less positive and more negative interpersonal experiences, and greater cigarette and drug use. Most effect sizes were in the medium-small range. Associations of youth- and parent-reported irritability at ages 12 and 15 with the age 18 EMA measures were generally similar, although smaller in magnitude. Findings contribute to understanding how irritability is manifested in real-time affect dynamics and interpersonal functioning, as well as daily substance use. Most effects were evident over the course of up to 6 years - that is, early adolescent irritability, reported by both youth and their parents, was associated with similar real-time affect dynamics and interpersonal experiences at age 18. This study contributes to the literature on the developmental psychopathology of irritability by extending findings to everyday functioning.

Nonpharmacological interventions on glycated haemoglobin in youth with type 1 diabetes: a Bayesian network meta-analysis.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

Fetal femur length and risk of diabetes in adolescence: a prospective cohort study.

BACKGROUND: Diabetes is more apparent in adulthood but may be dormant in childhood and originates during early fetal development. In fetal biometry, femur length (FL) is crucial for assessing fetal growth and development. This study aimed to assess potential associations between fetal femur growth and prediabetic biomarkers in Bangladeshi children. METHODS: A cohort study embedded in a population-based maternal food and micronutrient supplementation (MINIMat) trial was conducted in Matlab, Bangladesh. The children in the cohort were followed up until 15 years of age. In the original trial, pregnancy was confirmed by ultrasound before 13 gestational weeks (GWs). Afterward, ultrasound assessments were performed at 14, 19, and 30 GWs. FL was measured from one end to the other, capturing a complete femoral image. The FL was standardized by GW, and a z-score was calculated. FBG and HbA1c levels were determined in plasma and whole blood, and the triglyceride-glucose index, a biomarker of insulin resistance, was calculated as Ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable linear regression analysis using a generalized linear model was performed to estimate the effects of FL at 14, 19 and 30 GWs on prediabetic biomarkers at 9 and 15 years of age. Maternal micronutrient and food supplementation group, parity, child sex, and BMI at 9 years or 15 years were included as covariates. RESULTS: A total of 1.2% (6/515) of the participants had impaired fasting glucose during preadolescence, which increased to 3.5% (15/433) during adolescence. At 9 years, 6.3% (32/508) of the participants had elevated HbA1c%, which increased to 28% (120/431) at 15 years. Additionally, the TyG index increased from 9.5% (49/515) (during preadolescence) to 13% (56/433) (during adolescence). A one standard deviation decrease in FL at 14 and 19 GWs was associated with increased FBG (ß = - 0.44 [- 0.88, - 0.004], P = 0.048; ß = - 0.59 [- 1.12, - 0.05], P = 0.031) and HbA1c (ß = - 0.01; [- 0.03, -0.005], P = 0.007; ß = - 0.01 [- 0.03, - 0.003], P = 0.018) levels at 15 years. FL was not associated with diabetic biomarkers at 9 years. CONCLUSION: Mid-trimester impaired femur growth may be associated with elevated prediabetic biomarkers in Bangladeshi adolescents.

Adolescent Health Risk Behaviors, Adverse Experiences, and Self-reported Hunger: Analysis of 10 States from the 2019 Youth Risk Behavior Surveys.

We examined associations between adolescent self-reported hunger, health risk behaviors, and adverse experiences during the 2018-2019 school year. Youth Risk Behavior Survey data were pooled from 10 states. Prevalence ratios were calculated, and we assessed effect measure modification by sex. The prevalence of self-reported hunger was 13%. Self-reported hunger was associated with a higher prevalence of every health risk behavior/adverse experience analyzed, even after adjusting for sex, grade, and race/ethnicity. Sex did not modify associations. Findings underscore needs for longitudinal research with more robust measures of adolescent food insecurity to clarify the temporality of relationships.

Effects of Pollution Burden on Neural Function During Implicit Emotion Regulation and Longitudinal Changes in Depressive Symptoms in Adolescents.

Background: Exposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; however, the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9-13 years) was associated with altered brain activation and connectivity during implicit emotion regulation and changes in depressive symptoms across adolescence. Methods: One hundred forty-five participants (n = 87 female; 9-13 years) provided residential addresses, from which we determined their relative pollution burden at the census tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at 3 time points, each approximately 2 years apart, from which we calculated within-person slopes of depressive symptoms. We conducted whole-brain activation and connectivity analyses to examine whether pollution burden was associated with alterations in brain function during implicit emotion regulation of positively and negatively valenced stimuli and how these effects were related to slopes of depressive symptoms across adolescence. Results: Greater pollution burden was associated with greater bilateral medial prefrontal cortex activation and stronger bilateral medial prefrontal cortex connectivity with regions within the default mode network (e.g., temporoparietal junction, posterior cingulate cortex, precuneus) during implicit regulation of negative emotions, which was associated with greater increases in depressive symptoms across adolescence in those exposed to higher pollution burden. Conclusions: Adolescents living in communities characterized by greater pollution burden showed altered default mode network functioning during implicit regulation of negative emotions that was associated with increases in depressive symptoms across adolescence.

Exposure to environmental pollution is related to increased risk for depression in youth; however, the neurobiological mechanisms underlying this association are unknown. We found that adolescents living in neighborhoods with greater census tract­level pollution burden had stronger functional connectivity between the medial prefrontal cortex and regions within the default mode network during implicit regulation of negative emotions, which in turn was associated with greater increases in depressive symptoms across adolescence in these pollution-exposed youths.

Nutritional and physical fitness parameters in adolescence impact cardiovascular health in adulthood.

BACKGROUND & AIMS: Cardiovascular diseases are the leading cause of mortality worldwide, originating in the first decades of life. A better understanding of their early determinants would allow for better prevention. This study aimed to evaluate the impact of nutritional and activity-related characteristics during adolescence on young adult cardiovascular risk factors. METHODS: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study included adolescents (aged 12.5-17.5 years) in 10 European centres. Four centres designed a nested cohort including 236 participants who were reassessed as young adults (21-32 years). Food consumption was evaluated by dietary recalls, physical activity by accelerometers, physical fitness using physical tests and nutritional knowledge by questionnaires. Cardiovascular health was assessed by Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study risk scores and its components. Factors associated with cardiovascular risk were identified using a multivariable regression model. RESULTS: Higher Diet Quality Index (DQI, P = 0.012) and nutritional knowledge (P = 0.015) were significantly associated with lower modified PDAY risk scores. Ultra-processed foods were associated with a lower non-high-density lipoprotein (non-HDL) cholesterol (P = 0.003), whereas DQI (P = 0.014) and Planetary Health Diet Index (P = 0.016) were associated with a higher HDL cholesterol. Higher DQI was also related to a lower body mass index (BMI, P = 0.006). In addition, cardiorespiratory fitness was related to a lower BMI (P = 0.004). CONCLUSIONS: Nutritional knowledge, diet quality and adherence to a sustainable diet in adolescence decrease cardiovascular risk in adulthood, whereas ultra-processed food consumption increases risk. These factors appear as targeted prevention tools for promoting a healthier adolescent lifestyle to decrease long-term cardiovascular risk. CLINICAL TRIAL REGISTRY NUMBER: Clinicaltrials.gov NCT02899416.

Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

Selective Classes and Early Health Inequalities in Comprehensive Schools in Finland.

BACKGROUND: The origin of inequalities in health outcomes has been explained by health selection and social causation models. Health selection processes operate particularly at school age. We study, if student allocation to teaching groups with aptitude tests (selective vs general class) differentiates adolescents by health behaviors and mental health. METHODS: Finnish schoolchildren 12-13 years from 12 selective classes, n = 248; 41 general classes, n = 703 answered a questionnaire on addictive products (tobacco, snus, alcohol, and energy drinks), digital media use, and mental health (health complaints, anxiety, and depression). Structural equation modeling was conducted to identify structures between outcomes, SEP (socioeconomic position), class type, and academic performance. RESULTS: Students in the selective classes reported less addictive digital media and addictive products use than students in the general classes. Differences in academic performance or SEP between the class types did not solely explain these differences. Mental health was not related to the class type. SEP was indirectly associated with health behaviors via the class type and academic performance. CONCLUSIONS: Selecting students to permanent teaching groups with aptitude tests differentiates students according to risky health behaviors. The impact of education policies using student grouping should also be evaluated in terms of students' health.

Types of leisure-time physical activity participation in childhood and adolescence, and physical activity behaviours and health outcomes in adulthood: a systematic review.

BACKGROUND: Youth leisure-time physical activity participation benefits physical activity habits and health outcomes later in life. However, it is unknown if certain types of leisure-time physical activity contribute to these benefits in different ways; this knowledge could enhance public health efforts. This systematic review aimed to synthesise evidence of the longitudinal associations between childhood and adolescent leisure-time physical activity on adulthood physical activity behaviours and health outcomes. METHODS: A systematic search of the literature was conducted across five databases from inception to July 2022. English, peer-reviewed observational studies with a minimum of two timepoints of data collection were eligible for inclusion. We included studies that investigated the association between participation in leisure-time physical activity types in children and adolescents (i.e., 5-18 years), and physical activity, mental health, or cardiovascular outcomes in adulthood (i.e., ≥ 18 years). RESULTS: Fourteen studies were included in the review, totalling 34,388 observations across five countries. Running in adolescence was associated with increased adulthood physical activity in both sexes, while sports involvement was associated with an increase in physical activity in males only. Adolescent team sports participation was associated with reduced odds of early adulthood depression, with varying findings for anxiety disorders. There was preliminary evidence of minimum threshold requirements for participation in certain activities before associations with future physical activity or health outcome benefits were observed. CONCLUSIONS: Preliminary findings suggest that the lifelong behavioural and health benefits of adolescent participation in leisure-time physical activity appear to be related to the type of activity undertaken, with potential differences between sexes. With the rarity of longitudinal studies spanning from childhood into adulthood, these findings provide important insights for public health strategies to optimise lifelong health and physical activity participation. PROSPERO REGISTRATION: CRD42022347792.

Early life adversities, psychopathologies and novel pharmacological strategies.

Exposure to adversities during early life stages (early life adversities - ELA), ranging from pregnancy to adolescence, represents a major risk factor for the vulnerability to mental disorders. Hence, it is important to understand the molecular and functional underpinning of such relationship, in order to develop strategies aimed at reducing the psychopathologic burden associated with ELA, which may eventually lead to a significant improvement in clinical practice. In this review, we will initially recapitulate clinical and preclinical evidence supporting the link between ELA and psychopathology and we will primarily discuss the main biological mechanisms that have been described as potential mediators of the effects of ELA on the psychopathologic risk, including the role for genetic factors as well as sex differences. The knowledge emerging from these studies may be instrumental for the development of novel therapeutic strategies aimed not only at correcting the deficits that emerge from ELA exposure, but also in preventing the manifestation of a full-blown psychopathologic condition. With this respect, we will specifically focus on adolescence as a key time frame for disease onset as well as for early therapeutic intervention. We believe that incorporating clinical and preclinical research data in the context of early life adversities can be instrumental to elucidate the mechanisms contributing to the risk for psychopathology or that may promote resilience. This will ultimately allow the identification of 'at risk' individuals who may benefit from specific forms of interventions that, by interfering with disease trajectories, could result in more benign clinical outcomes.

Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.

Background: Neurodevelopmental disorders (NDDs) can cause debilitating impairments in social cognition and aberrant functional connectivity in large-scale brain networks, leading to social isolation and diminished everyday functioning. To facilitate the treatment of social impairments, animal models of NDDs that link N- methyl-D-aspartate receptor (NMDAR) hypofunction to social deficits in adulthood have been used. However, understanding the etiology of social impairments in NDDs requires investigating social changes during sensitive windows during development. Methods: We examine social behavior during adolescence using a translational mouse model of NMDAR hypofunction (SR-/-) caused by knocking out serine racemase (SR), the enzyme needed to make D-serine, a key NMDAR coagonist. Species-typical social interactions are maintained through brain-wide neural activation patterns; therefore, we employed whole-brain cFos activity mapping to examine network-level connectivity changes caused by SR deletion. Results: In adolescent SR-/- mice, we observed disinhibited social behavior toward a novel conspecific and rapid social habituation toward familiar social partners. SR-/- mice also spent more time in the open arm of the elevated plus maze which classically points to an anxiolytic behavioral phenotype. These behavioral findings point to a generalized reduction in anxiety-like behavior in both social and non-social contexts in SR-/- mice; importantly, these findings were not associated with diminished working memory. Inter-regional patterns of cFos activation revealed greater connectivity and network density in SR-/- mice compared to controls. Discussion: These results suggest that NMDAR hypofunction - a potential biomarker for NDDs - can lead to generalized behavioral disinhibition in adolescence, potentially arising from disrupted communication between and within salience and default mode networks.

Needs of transgender children and adolescents presenting to an urban gender health program.

BACKGROUND: Youth who identify as transgender and gender diverse (TGD) are increasingly presenting to pediatric providers. Gender-affirming surgery is often delayed until after a patient reaches the age of majority; however, patients may desire surgery at a younger age. OBJECTIVE: We explore the specific clinical needs of this vulnerable population, including surgical requests. STUDY DESIGN: We present a cross-sectional study of patient intake interviews at time of presentation to our gender health program from 2017 to 2020. We summarize patient demographics, medical histories, and gender-affirming care needs by gender identity and age of presentation. RESULTS: Of 92 patients analyzed, those included were 19 trans girls, 55 trans boys, and 18 non-binary individuals. The median age of our sample was 15 (range 5-17). The median age (IQR) while first questioning gender was 10 (7-12). Sexual orientation was variable with 28 (43%) not sure/unknown. The majority of patients present for primary care services (grade schoolers 75%, early teens 78%, and late teens 77%, p = 0.97) and hormone management (grade schoolers 42%, early teens 62%, and late teens 77%, p = 0.06). Late teens were more likely to present for surgical services (49%) compared to grade schoolers (25%) and early teens (11%), p = 0.001. Prior psychiatric diagnoses were common in all age groups. Trans girls were interested in a variety of affirming procedures whereas trans boys and non-binary individuals primarily sought chest surgery (see summary figure). CONCLUSION: Pediatric gender affirming care needs are varied and multidisciplinary within our center. By age 16, about half of TGD individuals are seeking surgical services. On average, there was a 4-5 year delay from age at first questioning one's gender and presenting to our gender health program. Primary care physicians in particular may prepare to serve this complex population by familiarizing themselves with treatment needs, including developing a network of competent surgical referrals.