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Adolescent depression is linked to adult ill-health and functional impairment, but recent research suggests that individual/contextual factors might account for this association. This study aimed to test whether the clinical heterogeneity of adolescent depression is related to marginalization from the labor market across early to middle adulthood. Data were drawn from the Uppsala Longitudinal Adolescent Depression Study, a community-based cohort initially assessed with structured clinical interviews at age 16-17. The cohort (n = 321 depressed; n = 218 nondepressed) was followed up after 2+ decades through linkage to nationwide population-based registries. Outcomes included consecutive annual data on unemployment, work disability, social welfare recipiency, and a composite marginalization measure, spanning from age 21 to 40. Longitudinal associations were examined using logistic regression analysis in a generalized estimating equations modeling framework. Subsequent depressive episodes and educational attainment in early adulthood were explored as potential pathways. The results showed that adolescent depression was associated with adult marginalization outcomes, but the strength of association varied across depressed subgroups. Adolescents with persistent depressive disorder had higher odds of all outcomes, including the composite marginalization measure (adjusted OR = 2.0, 95% CI = 1.4-2.7, p < 0.001), and this was partially (31%) mediated by subsequent depressive episodes in early adulthood. Exploratory moderation analysis revealed that entry into tertiary education mitigated the association with later marginalization, but only for adolescents with episodic major depression. In conclusion, the risk for future labor market marginalization is elevated among depressed adolescents, particularly those presenting with persistent depressive disorder. Targeted interventions seem crucial to mitigate the long-lasting impact of early-onset depression.

PURPOSE: Depression at all ages is recognized as a global public health concern, but less is known about the welfare burden following early-life depression. This study aimed to (1) estimate the magnitude of associations between depression in adolescence and social transfer payments in adulthood; and (2) address the impact of major comorbid psychopathology on these associations.

METHODS: This is a longitudinal cohort study of 539 participants assessed at age 16-17 using structured diagnostic interviews. An ongoing 25-year follow-up linked the cohort (n = 321 depressed; n = 218 nondepressed) to nationwide population-based registries. Outcomes included consecutive annual data on social transfer payments due to unemployment, work disability, and public assistance, spanning from age 18 to 40. Parameter estimations used the generalized estimating equations approach.

RESULTS: Adolescent depression was associated with all forms of social transfer payments. The estimated overall payment per person and year was 938 USD (95% CI 551-1326) over and above the amount received by nondepressed controls. Persistent depressive disorder was associated with higher recipiency across all outcomes, whereas the pattern of findings was less clear for subthreshold and episodic major depression. Moreover, depressed adolescents presenting with comorbid anxiety and disruptive behavior disorders evidenced particularly high recipiency, exceeding the nondepressed controls with an estimated 1753 USD (95% CI 887-2620).

CONCLUSION: Adolescent depression is associated with considerable public expenditures across early-to-middle adulthood, especially for those exposed to chronic/persistent depression and psychiatric comorbidities. This finding suggests that the clinical heterogeneity of early-life depression needs to be considered from a longer-term societal perspective.

Background: Prior research has shown that poor family relations during upbringing have long-term detrimental effects on mental health. Few previous studies have, however, focused on somatic health outcomes and studies rarely cover the life span until retirement age. The aims of the current study were, firstly, to examine the association between poor family relationships in adolescence and in-patient somatic care across the life course whilst adjusting for confounders at baseline and concurrent psychiatric in-patient care; and secondly, to compare the risks of somatic and psychiatric in-patient care across the life course.

Methods: Prospective data from the Stockholm Birth Cohort study were used, with 2636 participants born in 1953 who were followed up until 2016. Information on family relationships was collected from the participants' mothers in 1968. Annual information on in-patient somatic and psychiatric care was retrieved from official register data from 1969 to 2016.

Results: Poisson regressions showed that poor family relationships in adolescence were associated with an increased risk of in-patient somatic care in mid- and especially in late adulthood (ages 44-53 and 54-63 years), even when controlling for the co-occurrence of psychiatric illness and a range of childhood conditions. No statistically significant association was observed in early adulthood (ages 16-43 years), when controlling for confounders. These findings are in sharp contrast to the analyses of inpatient psychiatric care, according to which the association with poor family relations was strongest in early adulthood and thereafter attenuated across the life course.

Conclusion: Poor family relationships in adolescence are associated with an increased risk of severe consequences for somatic health lasting to late adulthood even when controlling for confounders including in-patient psychiatric care, emphasising the potentially important role of early interventions.

While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs.

Objective: Depression is common, impairing, and the leading cause of disease burden in youths. This study aimed to identify the effects of childhood/adolescent depression on a broad range of longer-term outcomes.

Method: The analysis is based on the prospective, representative Great Smoky Mountains Study of 1,420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to 8 times in childhood (age 9 similar to 16 years; 6,674 observations; 1993-2000) for DSM-based depressive disorders, associated psychiatric comorbidities, and childhood adversities. Participants were followed up 4 times in adulthood (ages 19, 21, 25, and 30 years; 4,556 observations of 1,336 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric outcomes and functional outcomes.

Results: In all, 7.7% of participants met criteria for a depressive disorder in childhood/adolescence. Any childhood/adolescent depression was associated with higher levels of adult anxiety and illicit drug disorders and also with worse health, criminal, and social functioning; these associations persisted when childhood psychiatric comorbidities and adversities were accounted for. No sex-specific patterns were identified. However, timing of depression mattered: individuals with adolescent-onset depression had worse outcomes than those with child-onset. Average depressive symptoms throughout childhood and adolescence were associated with more adverse outcomes. Finally, specialty mental health service use was protective against adult diagnostic outcomes.

Conclusion: Early depression and especially persistent childhood/adolescent depressive symptoms have robust, lasting associations with adult functioning. Some of these effects may be attenuated by service use.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Neurofeedback (NF) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD) has been evaluated in several trials, but the specificity and generalizability of effects remain unclear. This four-arm randomized controlled trial evaluated the efficacy of Slow Cortical Potential (SCP; standard NF protocol) and Live Z-score (LZS; non-standard NF protocol) delivered in high-frequency format (five sessions per week during five weeks), compared to Working-memory training (WMT; active comparator) and Treatment-as-usual (TAU; passive comparator). N = 202 children/adolescents aged 9 to 17 years with ADHD participated. The primary outcome measure was multi-report (self-, teacher-, and parent-report) ADHD core symptoms on the Conners-3, assessed at baseline, posttreatment, and 6-months follow-up. Data were analyzed using a linear mixed model. Between-group differences were scarce and did not show a distinct pattern. Superiority of LZS over TAU at endpoint were observed for teacher-rated measures only, while significant differences between SCP and TAU were restricted to posttreatment measurements. Contrary to our expectations, LZS outperformed SCP at endpoint for teacher-rated hyperactivity (-5.37; 95% CI: -10.14 to -0.60; p = .028; d = -.36) and overall ADHD symptoms (-2.20; -4.18 to -0.22; p = .030; d = -.41). There was no indication that either form of NF was superior to WMT. No severe adverse events were reported during the trial, whereas transient stress-related problems were quite frequent. Overall, the results from this pragmatic trial do not provide convincing support for broad implementation of NF in child and adolescent psychiatric services. Future research should try to clarify for whom and under what circumstances NF might be a viable treatment option.

Objective: To evaluate the effects of neurocognitive training methods on targeted cognitive functions in children and adolescent with ADHD.

Method: A pragmatic four-arm randomized controlled trial compared two types of neurofeedback (Slow Cortical Potential and Live Z-score) and Working-memory training (WMT) with treatment as usual. N = 202 participants with ADHD aged 9 to 17 years were included. A battery of cognitive function tests was completed pretreatment, posttreatment, and after 6-months.

Results: The effects of WMT on spatial and verbal working-memory were superior to neurofeedback and treatment as usual at posttreatment, but only partially sustained at follow-up. No other consistent effects were observed. We found no clear indications that effects were moderated by ADHD presentation, ongoing medication, age, or sex.

Conclusion: The sustained effects of neurocognitive training on cognitive functioning in children and adolescents with ADHD may be limited. Future research should focus on more personalized forms of neurocognitive training.

Abnormal default mode network (DMN) connectivity has been found in schizophrenia and other psychotic disorders. However, there are limited studies on early onset psychosis (EOP), and their results show lack of agreement. Here, we investigated within-network DMN connectivity in EOP compared to healthy controls (HC), and its relationship to clinical characteristics. A sample of 68 adolescent patients with EOP (mean age 16.53 +/- 1.12 [SD] years, females 66%) and 95 HC (mean age 16.24 +/- 1.50 [SD], females 60%) from two Scandinavian cohorts underwent resting state functional magnetic resonance imaging (rsfMRI). A group independent component analysis (ICA) was performed to identify the DMN across all participants. Dual regression was used to estimate spatial maps reflecting each participant's DMN network, which were compared between EOP and HC using voxel-wise general linear models and permutation-based analyses. Subgroup analyses were performed within the patient group, to explore associations between diagnostic subcategories and current use of psychotropic medication in relation to connectivity strength. The analysis revealed significantly reduced DMN connectivity in EOP compared to HC in the posterior cingulate cortex, precuneus, fusiform cortex, putamen, pallidum, amygdala, and insula. The subgroup analysis in the EOP group showed strongest deviations for affective psychosis, followed by other psychotic disorders and schizophrenia. There was no association between DMN connectivity strength and the current use of psychotropic medication. In conclusion, the findings demonstrate weaker DMN connectivity in adolescent patients with EOP compared to healthy peers, and differential effects across diagnostic subcategories, which may inform our understanding of underlying disease mechanisms in EOP.

It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [11C]DASB and [11C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.

IMPORTANCE Increasing numbers of transgender and gender diverse children and adolescents have been referred to gender identity clinics in Sweden in the past decade, and previous studies have found an association between media attention and referral counts. Whether the tone of media stories is associated with referrals is not yet known.

OBJECTIVE To investigate whether positive or negative media coverage on transgender and gender diverse issues is associated with referral counts to child and adolescent gender identity clinics.

DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, referrals counts were collected from all 6 specialized gender identity clinics in Sweden, along with information on referral date, sex assigned at birth, and birth year. Participants were all individuals younger than 19 years, referred to a gender identity clinic between January 1, 2017, and December 31, 2019. Data were analyzed from May 2020 to September 2021.

EXPOSURES Exposures included 3 major media events related to transgender health care in 2019; 1 event was categorized as positive and 2 events were categorized as negative press coverage.

MAIN OUTCOMES AND MEASURES Referral counts before and after each of the 3 major media events were assessed, and the moderating association of sex assigned at birth and age was examined with stratified analyses. Weekly referral counts and trends were assessed with interrupted time series analysis.

RESULTS Among 1784 referrals (359 referrals [21.4%] among individuals aged <13 years; 1034 referrals [72.1%] among individuals assigned female at birth and 401 referrals [27.9%] among individuals assigned male at birth), a negative association between media coverage and referral counts was found for the first of the negative media events. In the 3 months following the event, referrals decreased by 25.4% (95% CI, -31.9% to -18.9%) overall, by 32.2% (95 CI, -41.8% to -22.8%) for individuals assigned female at birth, and by 25.3% (95 CI, -32.4% to -18.3%) for individuals aged 13 to 18 years. In the interrupted time series analysis, a mean weekly decrease of 3% in the referrals was observed in the extended time interval of 39 weeks (incidence rate ratio, 0.97; 95 CI, 0.95 to 0.99). For the other 2 media events, no changes in referral counts or time trends were observed.

CONCLUSIONS AND RELEVANCE These findings suggest that an event of negative media coverage on transgender-specific health care was negatively associated with access to health care for transgender children and adolescents; therefore, nuanced and accurate media coverage, as well as increased awareness of these mechanisms among key stakeholders, is essential.