Research Review: Integrated healthcare for children and young people in secondary/tertiary care - a systematic review.

BACKGROUND: Children and young people (CYP) with comorbid physical and/or mental health conditions often struggle to receive a timely diagnosis, access specialist mental health care, and more likely to report unmet healthcare needs. Integrated healthcare is an increasingly explored model to support timely access, quality of care and better outcomes for CYP with comorbid conditions. Yet, studies evaluating the effectiveness of integrated care for paediatric populations are scarce. AIM AND METHODS: This systematic review synthesises and evaluates the evidence for effectiveness and cost-effectiveness of integrated care for CYP in secondary and tertiary healthcare settings. Studies were identified through systematic searches of electronic databases: Medline, Embase, PsychINFO, Child Development and Adolescent Studies, ERIC, ASSIA and British Education Index. FINDINGS: A total of 77 papers describing 67 unique studies met inclusion criteria. The findings suggest that integrated care models, particularly system of care and care coordination, improve access and user experience of care. The results on improving clinical outcomes and acute resource utilisation are mixed, largely due to the heterogeneity of studied interventions and outcome measures used. No definitive conclusion can be drawn on cost-effectiveness since studies focused mainly on costs of service delivery. The majority of studies were rated as weak by the quality appraisal tool used. CONCLUSIONS: The evidence of on clinical effectiveness of integrated healthcare models for paediatric populations is limited and of moderate quality. Available evidence is tentatively encouraging, particularly in regard to access and user experience of care. Given the lack of specificity by medical groups, however, the precise model of integration should be undertaken on a best-practice basis taking the specific parameters and contexts of the health and care environment into account. Agreed practical definitions of integrated care and associated key terms, and cost-effectiveness evaluations are a priority for future research.

Action selection in early stages of psychosis: an active inference approach.

BACKGROUND: To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls. METHODS: Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification. RESULTS: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures. LIMITATIONS: The sample size is moderate. CONCLUSION: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis.

Shorter sleep among adolescents is associated with lower fruit and vegetable consumption the following day.

BACKGROUND: Insufficient sleep has been associated with weight gain and metabolic dysregulation, with one suggested mechanism being through reduction in diet quality. Experimental evidence supports a causal effect of sleep timings on diet but this may not be applicable to a free-living adolescent population. In this analysis we use daily measures of sleep timings and diet quality, to examine the effect of sleep duration and timing on diet quality the following day among free-living adolescents. METHODS: The ROOTS study is a prospective cohort recruited from secondary schools in Cambridgeshire and Suffolk (UK). Participants (n = 815) at mean age 15.0y (SD 0.3y) completed a diet diary and wore a combined heart rate and accelerometer device over 4 consecutive days. Sleep duration and timing (midpoint) were derived from acceleration and heart rate traces, while daily energy density and fruit and vegetable intake were calculated from dietary data. Analyses were performed at day-level (1815 person-days). Multilevel random effects models were used to test associations between sleep each night and subsequent day diet, with daily sleep and diet measures nested within individuals and schools, and adjusted for day-level and individual-level confounding variables. RESULTS: Adolescents slept a mean of 7.88 hrs (SD 1.10) per night, reporting a mean energy density of 2.12 kcal/g (SD 0.48) and median energy-adjusted daily fruit and vegetable intake of 137.3 g (IQR 130.4). One hour shorter sleep duration was associated with lower intake of fruit and vegetables (-6.42 g, 95%CI -1.84, -10.99) the following day. An association with higher dietary energy density (0.016 kcal/g, 95%CI 0.034, -0.002) the following day was observed but did not reach statistical significance. Sleep timing was not associated with either fruit and vegetable intake (-2.52 g/d, 95%CI -7.66, 2.62) or dietary energy density (-0.001 kcal/g, 95%CI -0.022, 0.020). CONCLUSIONS: Our observational findings from a free-living adolescent population support the experimental evidence for a causal role of sleep on diet, with shorter sleep duration at night leading to a small decrease in diet quality the following day. These findings support experimental evidence to suggest inclusion of sleep duration as one component of interventions designed to improve diet quality and weight status in adolescents.

Resilient functioning is associated with altered structural brain network topology in adolescents exposed to childhood adversity.

Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.

Conservative and disruptive modes of adolescent change in human brain functional connectivity.

Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: "conservative" and "disruptive." Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman's correlation between edgewise baseline FC (at 14 y, [Formula: see text]) and adolescent change in FC ([Formula: see text]), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas.

Stratification of adolescents across mental phenomena emphasizes the importance of transdiagnostic distress: a replication in two general population cohorts.

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 3018) and the Neuroscience in Psychiatry Network (NSPN, n = 2023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, and psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention.

Behavioral measures of impulsivity and compulsivity in adolescents with nonsuicidal self-injury.

BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents. METHODS: Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms. RESULTS: Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity. CONCLUSIONS: Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.

Associations between COVID-19 pandemic impact, dimensions of behavior and eating disorders: A longitudinal UK-based study.

BACKGROUND: There is growing concern about how people with eating disorders are impacted by the widespread societal restructuring during the COVID-19 crisis. AIMS: We aimed to examine how factors relating to the impact of the pandemic associate with eating disorders and quantify this relationship while adjusting for concurrent and longitudinal parameters of risk. METHODS: We gathered demographic, behavioral and clinical data pre- and mid-pandemic as well as childhood trauma history from a longitudinal online survey of 489 adults (mean age 23.4 years) recruited from the Neuroscience in Psychiatry Network (NSPN). Using pre-pandemic (T1) and concurrent (T2) data we aimed to predict eating disorders at mid-pandemic (T2). We deployed hierarchical generalized logistic regression to ascertain the strength of longitudinal and concurrent associations. RESULTS: Pre-pandemic eating disorder scores strongly associated with concurrent eating disorder (z = 5.93). More conflict at home mid-pandemic (z = 2.03), pre- (lower sensation seeking z = -2.58) and mid-pandemic (higher lack of perseverance z = 2.33) impulsivity traits also associated with mid-pandemic eating disorder. CONCLUSION: Conflict at home mid-pandemic and specific aspects of impulsiveness significantly associated with concurrent eating disorder when adjusted for pre-pandemic eating disorder symptoms, baseline demographics, behavioral traits, history of traumatic experiences and concurrent psychopathology. These results provide insight into the struggles of those suffering with eating disorders during the COVID-19 pandemic and highlight the importance of impulsiveness traits and the immediate family environment in their experience of illness during the pandemic.

Cross-sectional and longitudinal associations between psychotic and depressive symptoms in depressed adolescents.

Adults with major depressive disorder (MDD) with psychotic features (delusions and/or hallucinations) have more severe symptoms and a worse prognosis. Subclinical psychotic symptoms are more common in adolescents than adults. However, the effects of psychotic symptoms on outcome of depressive symptoms have not been well studied in adolescents. Depressed adolescents aged 11-17 with and without psychotic symptoms were compared on depression severity scores at baseline and at 28- or 42-week follow-up in two large UK cohorts. Psychotic symptoms were weakly associated with more severe depression at baseline in both cohorts. At follow-up, baseline psychotic symptoms were only associated with depressive symptoms in one sample; in the other, the effect size was close to zero. This supports the DSM5 system of psychotic symptoms being a separate code to severity rather than the ICD10 system which only allows the diagnosis of psychotic depression with severe depression. There was no clear support for psychotic symptoms being a baseline marker of treatment response.

Depression symptom clusters in adolescents: A latent class analysis in a clinical sample.

BACKGROUND: Major depression is clinically heterogeneous. We aimed to identify classes of depressed adolescents with different symptom presentations and examine if these were differentially associated with illness severity, functioning, engagement with treatment, and clinical outcomes. METHOD: Baseline depression symptoms of 454 depressed adolescents (age 11-17) from the IMPACT trial were subjected to latent class analysis. We compared classes on self-reported symptoms and social impairment at baseline and follow-up and their engagement in treatment. RESULTS: We identified three classes of participants which differed in the number and pattern of depression symptoms; Class 1-Severe- (37.2%)-endorsed almost all symptoms and were most functionally impaired; Class 2-Moderate- (41.9%)-endorsed fewer symptoms with high suicidal ideation, self-harm, and worthlessness; Class 3-Somatic (20.9%)-endorsed fewest symptoms, with high somatic symptoms. Groups did not differ on engagement, therapeutic alliance, or post-treatment symptom reduction. Adolescents in the severe and moderate subgroups reported symptom reductions after treatment ended, whilst those in the somatic subgroup did not. CONCLUSIONS: At presentation, high somatic features in depressed adolescents, rather than severity, or impairment levels, may indicate lower liability for responding to psychological treatment.

Examining the relationship between altered brain functional connectome and disinhibition across 33 impulsive and compulsive behaviours.

Impulsive and compulsive problem behaviours are associated with a variety of mental disorders. Latent phenotyping indicates the expression of impulsive and compulsive problem behaviours is predominantly governed by a transdiagnostic 'disinhibition' phenotype. In a cohort of 117 individuals, recruited as part of the Neuroscience in Psychiatry Network (NSPN), we examined how brain functional connectome and network properties relate to disinhibition. Reduced functional connectivity within a subnetwork of frontal (especially right inferior frontal gyrus), occipital and parietal regions was linked to disinhibition. Findings provide insights into neurobiological pathways underlying the emergence of impulsive and compulsive disorders.

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood.

Adolescence is a time period associated with marked brain maturation that coincides with an enhanced risk for onset of psychiatric disorder. White matter tract myelination, a process that continues to unfold throughout adolescence, is reported to be abnormal in several psychiatric disorders. Here, we ask whether psychiatric vulnerability is linked to aberrant developmental myelination trajectories. We assessed a marker of myelin maturation, using magnetisation transfer (MT) imaging, in 10 major white matter tracts. We then investigated its relationship to the expression of a general psychopathology "p-factor" in a longitudinal analysis of 293 healthy participants between the ages of 14 and 24. We observed significant longitudinal MT increase across the full age spectrum in anterior thalamic radiation, hippocampal cingulum, dorsal cingulum and superior longitudinal fasciculus. MT increase in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus was pronounced in younger participants but levelled off during the transition into young adulthood. Crucially, longitudinal MT increase in dorsal cingulum and uncinate fasciculus decelerated as a function of mean p-factor scores over the study period. This suggests that an increased expression of psychopathology is closely linked to lower rates of myelin maturation in selective brain tracts over time. Impaired myelin growth in limbic association fibres may serve as a neural marker for emerging mental illness during the course of adolescence and early adulthood.

Childhood socio-economic disadvantage predicts reduced myelin growth across adolescence and young adulthood.

Socio-economic disadvantage increases exposure to life stressors. Animal research suggests early life stressors impact later neurodevelopment, including myelin developmental growth. To determine how early life disadvantage may affect myelin growth in adolescence and young adulthood, we analysed data from an accelerated longitudinal neuroimaging study measuring magnetisation transfer (MT), a myelin-sensitive marker, in 288 participants (149 female) between 14 and 25 years of age at baseline. We found that early life economic disadvantage before age 12, measured by a neighbourhood poverty index, was associated with slower myelin growth. This association was observed for magnetization transfer in cortical, subcortical and core white matter regions, and also in key subcortical nuclei. Participant IQ at baseline, alcohol use, body mass index, parental occupation and self-reported parenting quality did not account for these effects, but parental education did so partially. Specifically, positive parenting moderated the effect of socio-economic disadvantage in a protective manner. Thus, early socioeconomic disadvantage appears to alter myelin growth across adolescence. This finding has potential translational implications, including clarifying whether reducing socio-economic disadvantage during childhood, and increasing parental education and positive parenting, promote normal trajectories of brain development in economically disadvantaged contexts.

Toward precision therapeutics: general and specific factors differentiate symptom change in depressed adolescents.

BACKGROUND: The longitudinal course of multiple symptom domains in adolescents treated for major depression is not known. Revealing the temporal course of general and specific psychopathology factors, including potential differences between psychotherapies, may aid therapeutic decision-making. METHODS: Participants were adolescents with major depressive disorder (aged 11-17; 75% female; N = 465) who were part of the IMPACT trial, a randomized controlled trial comparing cognitive behavioral therapy, short-term psychoanalytic psychotherapy, and brief psychosocial intervention. Self-reported symptoms at baseline and 6, 12, 36, 52, and 86 weeks postrandomization were analyzed with bifactor modeling. RESULTS: General psychopathology factor scores decreased across treatment and one-year follow-up. Specific melancholic features and depressive cognitions factors decreased from baseline to 6 weeks. Conduct problems decreased across treatment and follow-up. Anxiety increased by 6 weeks and then reverted to baseline levels. Obsessions-compulsions did not change. Changes in general and specific factors were not significantly different between the three psychotherapies during treatment. During follow-up, however, conduct problems decreased more in brief psychosocial intervention versus cognitive behavioral therapy (1.02, 95% Bayes credible interval 0.25, 1.96), but not versus short-term psychoanalytic psychotherapy. CONCLUSIONS: The clinical response signature in this trial is best revealed by rapid reductions in depression symptoms and general psychopathology. Protracted improvements in general psychopathology and conduct problems subsequently occur. Psychosocial treatments for adolescent depression have comparable effects on general and specific psychopathology, although a psychoeducational, goal-focused approach may be indicated for youth with comorbid conduct problems.

Trajectories of depression symptom change during and following treatment in adolescents with unipolar major depression.

OBJECTIVE: To classify a cohort of depressed adolescents recruited to the UK IMPACT trial, according to trajectories of symptom change. We examined for predictors and compared the data-driven categories of patients with a priori operational definitions of treatment response. METHOD: Secondary data analysis using growth mixture modelling (GMM). Missing data were imputed. Trajectories of self-reported depressive symptoms were plotted using scores taken at six nominal time points over 86 weeks from randomisation in all 465 patients. RESULTS: A piecewise GMM categorised patients into two classes with initially similar and subsequently distinct trajectories. Both groups had a significant decline in depressive symptoms over the first 18 weeks. Eighty-four per cent (84.1%, n = 391) of patients were classed as 'continued-improvers' with symptoms reducing over the duration of the study. A further class of 15.9% (n = 74) of patients were termed 'halted-improvers' with higher baseline depression scores, faster early recovery but no further improvement after 18 weeks. Presence of baseline comorbidity somewhat increased membership to the halted-improvers class (OR = 1.40, CI: 1.00-1.96). By end of study, compared with classes, a clinical remission cut-off score (≤27) and a symptom reduction score (≥50%) indexing treatment response misclassified 15% and 31% of cases, respectively. CONCLUSIONS: A fast reduction in depressive symptoms in the first few weeks of treatment may not indicate a good prognosis. Halted improvement is only seen after 18 weeks of treatment. Longitudinal modelling may improve the precision of revealing differential responses to treatment. Improvement in depressive symptoms may be somewhat better in the year after treatment than previously considered.

Mood and neural responses to social rejection do not seem to be altered in resilient adolescents with a history of adversity.

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered "resilient"), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression.

Psychiatric disorders are associated with aberrant brain development and/or aggressive behavior and are influenced by genetic factors; however, genes that affect brain aggression circuits remain elusive. Here, we show that neuronal Src-homology-2 (SH2)B adaptor protein-1 ( Sh2b1) is indispensable for both brain growth and protection against aggression. Global and brain-specific deletion of Sh2b1 decreased brain weight and increased aggressive behavior. Global and brain-specific Sh2b1 knockout (KO) mice exhibited fatal, intermale aggression. In a resident-intruder paradigm, latency to attack was markedly reduced, whereas the number and the duration of attacks was significantly increased in global and brain-specific Sh2b1 KO mice compared with wild-type littermates. Consistently, core aggression circuits were activated to a higher level in global and brain-specific Sh2b1 KO males, based on c-fos immunoreactivity in the amygdala and periaqueductal gray. Brain-specific restoration of Sh2b1 normalized brain size and reversed pathologic aggression and aberrant activation of core aggression circuits in Sh2b1 KO males. SH2B1 mutations in humans were linked to aberrant brain development and behavior. At the molecular level, Sh2b1 enhanced neurotrophin-stimulated neuronal differentiation and protected against oxidative stress-induced neuronal death. Our data suggest that neuronal Sh2b1 promotes brain development and the integrity of core aggression circuits, likely through enhancing neurotrophin signaling.-Jiang, L., Su, H., Keogh, J. M., Chen, Z., Henning, E., Wilkinson, P., Goodyer, I., Farooqi, I. S., Rui, L. Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression.

Practitioner Review: Therapeutics of unipolar major depressions in adolescents.

BACKGROUND: Over the past two decades new and key randomized controlled trials have reported the efficacy, clinical and cost effectiveness of psychological and pharmacological treatments for adolescents with major depression. METHODS: The literature was searched through pubmed, psychinfo, scopus and web of science for randomized controlled trials of current major depression together with meta-analyses and systematic reviews of trials between 2000 and 2017. Those specific to the adolescent years (11-18 years) were taken as the primary source for this narrative review. Additional selected studies in adults were used to illustrate methodological issues. RESULTS: Manualized psychological therapies and the SSRI fluoxetine are more effective than active placebo in the treatment of major depressions. Mild to moderate illnesses attending community-based services are likely to benefit from psychological treatment alone. Moderately to severely ill patients attending clinic and hospital services are likely to benefit from monotherapies or combining psychological and pharmacological treatment. Antidepressants carry a small but significant side-effect risk including increased suicidality. Side effects from psychotherapies are somewhat lower but specific negative consequences remain less well characterized. There is some evidence that CBT-based approaches prevent onset of major depression episode in well adolescents at high-risk. Other psychological interventions have not been adequately studied. There has been only limited identification of treatment moderators and no clear understanding of therapeutic mechanisms. CONCLUSIONS: There is now a range of clinically effective treatments for depressed adolescents. Future research needs to reveal moderators of and mechanisms for individual differences to treatment response, determine psychotherapies of value for milder depressions, enhance our understanding of safety and side-effects for all treatments, and consider how to reduce and treat treatment-resistant cases.

Change, stability, and instability in the Pavlovian guidance of behaviour from adolescence to young adulthood.

Pavlovian influences are important in guiding decision-making across health and psychopathology. There is an increasing interest in using concise computational tasks to parametrise such influences in large populations, and especially to track their evolution during development and changes in mental health. However, the developmental course of Pavlovian influences is uncertain, a problem compounded by the unclear psychometric properties of the relevant measurements. We assessed Pavlovian influences in a longitudinal sample using a well characterised and widely used Go-NoGo task. We hypothesized that the strength of Pavlovian influences and other 'psychomarkers' guiding decision-making would behave like traits. As reliance on Pavlovian influence is not as profitable as precise instrumental decision-making in this Go-NoGo task, we expected this influence to decrease with higher IQ and age. Additionally, we hypothesized it would correlate with expressions of psychopathology. We found that Pavlovian effects had weak temporal stability, while model-fit was more stable. In terms of external validity, Pavlovian effects decreased with increasing IQ and experience within the task, in line with normative expectations. However, Pavlovian effects were poorly correlated with age or psychopathology. Thus, although this computational construct did correlate with important aspects of development, it does not meet conventional requirements for tracking individual development. We suggest measures that might improve psychometric properties of task-derived Pavlovian measures for future studies.

Adolescent Tuning of Association Cortex in Human Structural Brain Networks.

Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14-24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.