Transforming mental health systems globally: principles and policy recommendations.

A burgeoning mental health crisis is emerging globally, regardless of each country's human resources or spending. We argue that effectively responding to this crisis is impeded by the dominant framing of mental ill health through the prism of diagnostic categories, leading to an excessive reliance on interventions that are delivered by specialists; a scarcity of widespread promotive, preventive, and recovery-oriented strategies; and failure to leverage diverse resources within communities. Drawing upon a series of syntheses, we identify five principles to transform current practices; namely, address harmful social environments across the life course, particularly in the early years; ensure that care is not contingent on a categorical diagnosis but aligned with the staging model of mental illness; empower diverse front-line providers to deliver psychosocial interventions; embrace a rights-based approach that seeks to provide alternatives to violence and coercion in care; and centre people with lived experience in all aspects of care. We recommend four policy actions which can transform these principles into reality: a whole of society approach to prevention and care; a redesign of the architecture of care delivery to provide a seamless continuum of care, tailored to the severity of the mental health condition; investing more in what works to enhance the impact and value of the investments; and ensuring accountability through monitoring and acting upon a set of mental health indicators. All these actions are achievable, relying-for the most part-on resources already available to every community and country. What they do require is the acceptance that business as usual will fail and the solutions to transforming mental health-care systems are already present within existing resources.

How much or how often? Examining the screening properties of the DSM cross-cutting symptom measure in a youth population-based sample.

BACKGROUND: The DSM Level 1 Cross-Cutting Symptom Measure (DSM-XC) allows for assessing multiple psychopathological domains. However, its capability to screen for mental disorders in a population-based sample and the impact of adverbial framings (intensity and frequency) on its performance are unknown. METHODS: The study was based on cross-sectional data from the 1993 Pelotas birth cohort in Brazil. Participants with completed DSM-XC and structured diagnostic interviews (n = 3578, aged 22, 53.6% females) were included. Sensitivity, specificity, positive (LR+), and negative (LR-) likelihood ratios for each of the 13 DSM-XC domains were estimated for detecting five internalizing disorders (bipolar, generalized anxiety, major depressive, post-traumatic stress, and social anxiety disorders) and three externalizing disorders (antisocial personality, attention-deficit/hyperactivity, and alcohol use disorders). Sensitivities and specificities >0.75, LR+ > 2 and LR- < 0.5 were considered meaningful. Values were calculated for the DSM-XC's original scoring and for adverbial framings. RESULTS: Several DSM-XC domains demonstrated meaningful screening properties. The anxiety domain exhibited acceptable sensitivity and LR- values for all internalizing disorders. The suicidal ideation, psychosis, memory, repetitive thoughts and behaviors, and dissociation domains displayed acceptable specificity for all disorders. Domains also yielded small but meaningful LR+ values for internalizing disorders. However, LR+ and LR- values were not generally meaningful for externalizing disorders. Frequency-framed questions improved screening properties. CONCLUSIONS: The DSM-XC domains showed transdiagnostic screening properties, providing small but meaningful changes in the likelihood of internalizing disorders in the community, which can be improved by asking frequency of symptoms compared to intensity. The DSM-XC is currently lacking meaningful domains for externalizing disorders.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Adolescent depression beyond DSM definition: a network analysis.

Calls for refining the understanding of depression beyond diagnostic criteria have been growing in recent years. We examined the prevalence and relevance of DSM and non-DSM depressive symptoms in two Brazilian school-based adolescent samples with two commonly used scales, the Patient Health Questionnaire (PHQ-A) and the Mood and Feelings Questionnaire (MFQ). We analyzed cross-sectional data from two similarly recruited samples of adolescents aged 14-16 years, as part of the Identifying Depression Early in Adolescence (IDEA) study in Brazil. We assessed dimensional depressive symptomatology using the PHQ-A in the first sample (n = 7720) and the MFQ in the second sample (n = 1070). We conducted network analyses to study symptom structure and centrality estimates of the two scales. Additionally, we compared centrality of items included (e.g., low mood, anhedonia) and not included in the DSM (e.g., low self-esteem, loneliness) in the MFQ. Sad mood and worthlessness items were the most central items in the network structure of the PHQ-A. In the MFQ sample, self-hatred and loneliness, two non-DSM features, were the most central items and DSM and non-DSM items in this scale formed a highly interconnected network of symptoms. Furthermore, analysis of the MFQ sample revealed DSM items not to be more frequent, severe or interconnected than non-DSM items, but rather part of a larger network of symptoms. A focus on symptoms might advance research on adolescent depression by enhancing our understanding of the disorder.

Longitudinal associations between adolescents' individualised risk for depression and inflammation in a UK cohort study.

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity - a risk factor for MDD - becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigation of the links between individuals' constellation of MDD risk and subsequent inflammation. We therefore examined associations between individual risk for MDD calculated in early adolescence and levels of inflammation six years later. We use data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK birth cohort of 2,232 children followed to age 18 with 93% retention. Participants' individual risk for developing future MDD was calculated at age 12 using a recently developed prediction model comprising multiple psychosocial factors. Plasma levels of three inflammation biomarkers were measured at age 18: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to reflect the level of systemic chronic inflammation. MDD risk scores calculated at age 12 were positively associated with levels of suPAR (but not CRP or IL-6) at age 18 after adjusting for key covariates (b = 1.70, 95% CI = 0.46 - 2.95, p = 0.007). Adolescents at high risk of MDD (risk scores ≥ 90th centile) had significantly higher mean levels of suPAR six years later than adolescents who had been identified as low risk (risk scores ≤ 10th centile) (b = 0.41, 95% CI = 0.18 - 0.64, p < 0.001). Findings support the notion that childhood psychosocial risk for MDD leads to increased levels of low-grade inflammation. If replicated in studies with repeated assessments of inflammation biomarkers throughout childhood and adolescence, these findings would support targeted interventions to reduce inflammation, as measured by suPAR, for adolescents at high risk of MDD to potentially prevent development of depression and physical health problems related to chronic inflammation.

Reward- and threat-related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil.

BACKGROUND: Neuroimaging studies on adolescents at risk for depression have relied on a single risk factor and focused on adolescents in high-income countries. Using a composite risk score, this study aims to examine neural activity and connectivity associated with risk and presence of depression in adolescents in Brazil. METHODS: Depression risk was defined with the Identifying Depression Early in Adolescence Risk Score (IDEA-RS), calculated using a prognostic model that included 11 socio-demographic risk factors. Adolescents recruited from schools in Porto Alegre were classified into a low-risk (i.e., low IDEA-RS and no lifetime depression), high-risk (i.e., high IDEA-RS and no lifetime depression), or clinically depressed group (i.e., high IDEA-RS and depression diagnosis). One hundred fifty adolescents underwent a functional MRI scan while completing a reward-related gambling and a threat-related face-matching task. We compared group differences in activity and connectivity of the ventral striatum (VS) and amygdala during the gambling and face-matching tasks, respectively, and group differences in whole-brain neural activity. RESULTS: Although there was no group difference in reward-related VS or threat-related amygdala activity, the depressed group showed elevated VS activity to punishment relative to high-risk adolescents. The whole-brain analysis found reduced reward-related activity in the lateral prefrontal cortex of patients and high-risk adolescents compared with low-risk adolescents. Compared with low-risk adolescents, high-risk and depressed adolescents showed reduced threat-related left amygdala connectivity with thalamus, superior temporal gyrus, inferior parietal gyrus, precentral gyrus, and supplementary motor area. CONCLUSIONS: We identified neural correlates associated with risk and presence of depression in a well-characterized sample of adolescents. These findings enhance knowledge of the neurobiological underpinnings of risk and presence of depression in Brazil. Future longitudinal studies are needed to examine whether the observed neural patterns of high-risk adolescents predict the development of depression.

Mind the brain gap: The worldwide distribution of neuroimaging research on adolescent depression.

Adolescents comprise one fourth of the world's population, with about 90% of them living in low- and middle-income countries (LMICs). The incidence of depression markedly increases during adolescence, making the disorder a leading cause of disease-related disability in this age group. However, most research on adolescent depression has been performed in high-income countries (HICs). To ascertain the extent to which this disparity operates in neuroimaging research, a systematic review of the literature was performed. A total of 148 studies were identified, with neuroimaging data available for 4,729 adolescents with depression. When stratified by income group, 122 (82%) studies originated from HICs, while 26 (18%) were conducted in LMICs, for a total of 3,705 and 1,024 adolescents with depression respectively. A positive Spearman rank correlation was observed between country per capita income and sample size (rs=0.673, p = 0.023). Our results support the previous reports showing a large disparity between the number of studies and the adolescent population per world region. Future research comparing neuroimaging findings across populations from HICs and LMICs may provide unique insights to enhance our understanding of the neurobiological processes underlying the development of depression.

Predicting the risk of depression among adolescents in Nepal using a model developed in Brazil: the IDEA Project.

The burden of adolescent depression is high in low- and middle-income countries (LMICs), yet research into prevention is lacking. Development and validation of models to predict individualized risk of depression among adolescents in LMICs is rare but crucial to ensure appropriate targeting of preventive interventions. We assessed the ability of a model developed in Brazil, a middle-income country, to predict depression in an existing culturally different adolescent cohort from Nepal, a low-income country with a large youth population with high rates of depression. Data were utilized from the longitudinal study of 258 former child soldiers matched with 258 war-affected civilian adolescents in Nepal. Prediction modelling techniques were employed to predict individualized risk of depression at age 18 or older in the Nepali cohort using a penalized logistic regression model. Following a priori exclusions for prior depression and age, 55 child soldiers and 71 war-affected civilians were included in the final analysis. The model was well calibrated, had good overall performance, and achieved good discrimination between depressed and non-depressed individuals with an area under the curve (AUC) of 0.73 (bootstrap-corrected 95% confidence interval 0.62-0.83). The Brazilian model comprising seven matching sociodemographic predictors, was able to stratify individualized risk of depression in a Nepali adolescent cohort. Further testing of the model's performance in larger socio-culturally diverse samples in other geographical regions should be attempted to test the model's wider generalizability.

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. METHODS: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. RESULTS: Linear regression analyses demonstrated that the increasing number of COMT158Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (ß coefficient = 0.049, t = 2.189, p = 0.029, R2 = 0.012, and ß coefficient = 0.064, t = 2.832, p = 0.005, R2 = 0.008, respectively). The presence of both COMT158Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls. LIMITATIONS: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated. CONCLUSION: This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression.

MAP1B and NOS1 genes are associated with working memory in youths with attention-deficit/hyperactivity disorder.

Diverse efforts have been done to improve the etiologic understanding of mental disorders, such as attention-deficit/hyperactivity disorder (ADHD). It becomes clear that research in mental disorders needs to move beyond descriptive syndromes. Several studies support recent theoretical models implicating working memory (WM) deficits in ADHD complex neuropsychology. The aim of this study was to examine the association between rs2199161 and rs478597 polymorphisms at MAP1B and NOS1 genes with verbal working memory in children and adolescents with ADHD. A total of 253 unrelated ADHD children/adolescents were included. The sample was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria. Digit Span from the Wechsler Intelligence Scale for Children-Third Edition was used to assess verbal WM. The raw scores from both forward and backward conditions of Digit Span were summed and converted into scaled scores according to age. The means of scaled Digit Span were compared according to genotypes by ANOVA. Significant differences in Digit Span scores between MAP1B genotype groups (rs2199161: F = 5.676; p = 0.018) and NOS1 (rs478597: F = 6.833; p = 0.009) genes were detected. For both polymorphisms, the CC genotype carriers showed a worse performance in WM task. Our findings suggest possible roles of NOS1 and MAP1B genes in WM performance in ADHD patients, replicating previous results with NOS1 gene in this cognitive domain in ADHD children.

Predictors of persistence of ADHD into adulthood: a systematic review of the literature and meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) is traditionally conceptualized as a neurodevelopmental disorder that continues into adulthood in up to half of diagnosed cases. In light of current evidence, factors associated with the course of the disorder remain unknown. We performed a systematic review of the literature searching for risk markers from childhood that predicted the persistence of ADHD into adulthood. We reviewed 26,168 abstracts and selected 72 for full-text review. We identified data from 16 studies, comprising 6 population-based retrospective samples and 10 clinical follow-ups. We performed meta-analyses of factors evaluated by at least three studies. Severity of ADHD (OR 2.33, 95 % CI = 1.6-3.39, p < 0.001), treatment for ADHD (OR 2.09, 95 % CI = 1.04-4.18, p = 0.037), comorbid conduct disorder (OR 1.85, 95 % CI = 1.06-3.24, p = 0.030), and comorbid major depressive disorder (OR 1.8, 95 % CI = 1.1-2.95, p = 0.019) emerged as predictors already presented in childhood for ADHD persistence into adulthood. Further, we suggest that cohort studies should be designed to clarify such an important question for research and clinical practice.

Cadherin-13 gene is associated with hyperactive/impulsive symptoms in attention/deficit hyperactivity disorder.

Several efforts have been made to find new genetic risk variants which explain the high heritability of ADHD. At the genome level, genes involved in neurodevelopmental pathways were pointed as candidates. CDH13 and CTNNA2 genes are within GWAS top hits in ADHD and there are emerging notions about their contribution to ADHD pathophysiology. The main goal of this study is to test the association between SNPs in CDH13 and CTNNA2 genes and ADHD across the life cycle in subjects with ADHD. This study included 1,136 unrelated ADHD cases and 946 individuals without ADHD. No significant association between CDH13 and CTNNA2 was observed between cases and controls across different samples (P ≥ 0.096 for all comparisons). No allele was significantly more transmitted than expected from parents to ADHD probands. The CDH13 rs11150556 CC genotype was associated with more hyperactive/impulsive symptoms in youths with ADHD (children/adolescents clinical sample: F = 7.666, P = 0.006, FDR P-value = 0.032; Pelotas Birth Cohort sample: F = 6.711, P = 0.011, FDR P-value = 0.032). Although there are many open questions regarding the role of neurodevelopmental genes in ADHD symptoms, the present study suggests that CDH13 is associated with hyperactive/impulsive symptoms in youths with ADHD.

Searching for the best approach to assess teachers' perception of inattention and hyperactivity problems at school.

Although major guidelines in the field and current diagnostic criteria clearly demand an assessment of children's attention deficit/hyperactivity disorder (ADHD) symptoms at school, few studies address the fundamental question of which is the best approach for clinicians to get this information from teachers. Three screening strategies for ADHD were applied to teachers of 247 third grade students. They were asked (1) an overt question about potential cases of ADHD in their classroom; (2) to complete a broad-band questionnaire assessing common child mental health problems; (3) to rate ADHD-specific symptoms in a narrow-band questionnaire. Based on the overt question, teachers identified one in five students (21.1 %) as having ADHD; 28 cases (11.3 %) were identified using standard cut-offs for the narrow-band, and 13 (5.3 %) using a standard threshold for the sub-scale of hyperactivity from the broad-band questionnaire. Agreement among strategies was low (k = 0.28). A subsample of students, clinically assessed to confirm screenings, showed modest agreement with final diagnosis. The narrow-band questionnaire had the best diagnostic performance. Multivariate analysis indicated that the presence of a comorbid externalizing disorder was the only variable associated with teachers' ascertainment of ADHD caseness or non-caseness. Choice of screening strategy significantly affects how teachers report on ADHD symptoms at school. The halo effect of externalizing behaviors impacts the correct identification of true cases of ADHD in the school setting. Clinicians can rely on narrow-band instruments like the SNAP-IV to get information on ADHD symptoms at school from teachers.

ADHD pharmacogenetics across the life cycle: New findings and perspectives.

Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous disorder, affecting individuals across the life cycle. Although its etiology is not yet completely understood, genetics plays a substantial role. Pharmacological treatment is considered effective and safe for children and adults, but there is considerable inter-individual variability among patients regarding response to medication, required doses, and adverse events. We present here a systematic review of the literature on ADHD pharmacogenetics to provide a critical discussion of the existent findings, new approaches, limitations, and recommendations for future research. Our main findings are: first, the number of studies continues to grow, making ADHD one of the mental health areas with more pharmacogenetic studies. Second, there has been a focus shift on ADHD pharmacogenetic studies in the last years. There is an increasing number of studies assessing gene-gene and gene-environment interactions, using genome-wide association approaches, neuroimaging, and assessing pharmacokinetic properties. Third and most importantly, the heterogeneity in methodological strategies employed by different studies remains impressive. The question whether pharmacogenetics studies of ADHD will improve clinical management by shifting from trial-and-error approach to a pharmacological regimen that takes into account the individual variability remains unanswered. © 2014 Wiley Periodicals, Inc.

Glutamatergic copy number variants and their role in attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with a strong genetic component. The glutamate metabotropic receptor genes (GRMs) have been considered potential candidates for ADHD susceptibility. The aim of the present study was to investigate if copy number variants (CNVs) in GRM1, GRM5, and GRM8 genes are overrepresented in ADHD subjects. A total of 1038 individuals with ADHD and 1057 subjects without this disorder were investigated. No significant difference in the total number of CNVs was found comparing the entire ADHD sample and the population sample without ADHD (P = 0.326, OR = 1.112, 95% CI = 0.762-1.624). The presence of CNVs was associated with lower intelligence quotient (IQ) scores in ADHD samples (P = 0.026, OR = 1.824, 95% CI = 1.066-3.121) but not in the sample of individuals without ADHD. CNVs in GRM5 were associated with presence of anxiety disorders in ADHD cases (P = 0.002, OR = 3.915, 95% CI = 1.631-9.402), but not in individuals without ADHD. Taken together, our results suggest a role for glutamate in ADHD as CNVs in the glutamatergic genes investigated herein were associated with cognitive and clinical characteristics of ADHD individuals.

Systematic Review and Meta-Synthesis: How Is Depression Experienced by Adolescents? A Synthesis of the Qualitative Literature.

OBJECTIVE: To systematically investigate how youth with lived experience report their experience of depression in terms of features of depression and in relation to themselves and their environment. METHOD: We conducted a systematic review of qualitative research around the world that explored the subjective experience of depression among youth (age range, 10-24 years) who had self-reported, screened positive for, or received a formal diagnosis of the disorder. We used multiple databases to search for relevant studies published in any language up until March 2023. Studies were coded regarding features of depression reported by adolescents. We also used thematic synthesis to extract and synthesize descriptions of the lived experience of depression, and to develop analytic themes. The study was registered with PROSPERO, CRD42021218300. RESULTS: We identified a total of 23,424 unique records, and included 39 studies in the final review, representing the views of 884 adolescents with lived experience of depression. Most of the studies were conducted in high-income countries (72.8%), and the majority of participants were female (65%). The most frequently reported features of depression were sadness (present in 92.3% of the studies), social withdrawal (76.9%), and loneliness (69.2%). In addition, we constructed 3 themes that aimed to synthesize youths' accounts of their perceptions and experiences of depression: (1) making sense; (2) factoring in culture and contextual influences; and (3) accessing support and care. CONCLUSION: Some of the more commonly reported features of depression among youth are not explicitly included in the DSM/ICD diagnostic criteria but are highly relevant and closely connected to the experiences of adolescents. Moreover, contextual interpretations of depression may be more sensitive to capture representations and narratives of depression among youth. Thus, incorporating features of depression reported by adolescents could potentially increase accuracy of detection, promote collaborative work, and enhance therapeutic and care outcomes. STUDY PREREGISTRATION INFORMATION: The lived experience of depression in adolescence: a systematic review of the qualitative literature; https://www.crd.york.ac.uk/prospero/; CRD42021218300.