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The free energy principle is a formal theory of adaptive self-organising systems that emerged from statistical thermodynamics, machine learning and theoretical neuroscience and has since been translated into biologically plausible 'process theories' of cognition and behaviour, which fall under the banner of 'active inference'. Despite the promise this theory holds for theorising, research and practical applications in psychology and psychiatry, its impact on these disciplines has only now begun to bear fruit. The aim of this treatment is to consider the extent to which active inference has informed theoretical progress in psychology, before exploring its contributions to our understanding and treatment of psychopathology. Despite facing persistent translational obstacles, progress suggests that active inference has the potential to become a new paradigm that promises to unite psychology's subdisciplines, while readily incorporating the traditionally competing paradigms of evolutionary and developmental psychology. To date, however, progress towards this end has been slow. Meanwhile, the main outstanding question is whether this theory will make a positive difference through applications in clinical psychology, and its sister discipline of psychiatry. [ABSTRACT FROM AUTHOR]

Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo. One hundred seven young people with moderate to severe depression and 94 healthy control participants completed a functional magnetic resonance imaging cognitive reappraisal task. After the task, 87 participants with depression were randomized and received 12 weeks of cognitive behavioral therapy plus either fluoxetine or placebo. Dynamic causal modeling was used to map frontoamygdalar effective connectivity during reappraisal and to assess the predictive capacity of baseline frontoamygdalar effective connectivity on depression diagnosis and posttreatment depression remission. Young people with depression showed weaker inhibitory modulation of ventrolateral prefrontal cortex to amygdala connectivity during reappraisal (0.29 Hz, posterior probability = 1.00). Leave-one-out cross-validation demonstrated that this effect was sufficiently large to predict individual diagnostic status (r = 0.20, p =.003). Posttreatment depression remission was associated with weaker excitatory ventromedial prefrontal cortex to amygdala connectivity (−0.56 Hz, posterior probability = 1.00) during reappraisal at baseline, though this effect did not predict individual remission status (r = −0.02, p =.561). Frontoamygdalar effective connectivity shows promise in identifying youth depression diagnosis, and circuits responsible for negative affect regulation are implicated in responsiveness to first-line depression treatments. [ABSTRACT FROM AUTHOR]

Background: Suppression of the rostral anterior cingulate cortex (rACC) has shown promise as a prognostic biomarker for depression. We aimed to use machine learning to characterise its ability to predict depression remission. Methods: Data were obtained from 81 15- to 25-year-olds with a major depressive disorder who had participated in the YoDA-C trial, in which they had been randomised to receive cognitive behavioural therapy plus either fluoxetine or placebo. Prior to commencing treatment patients performed a functional magnetic resonance imaging (fMRI) task to assess rACC suppression. Support vector machines were trained on the fMRI data using nested cross-validation, and were similarly trained on clinical data. We further tested our fMRI model on data from the YoDA-A trial, in which participants had completed the same fMRI paradigm. Results: Thirty-six of 81 (44%) participants in the YoDA-C trial achieved remission. Our fMRI model was able to predict remission status (AUC = 0.777 [95% confidence interval (CI) 0.638–0.916], balanced accuracy = 67%, negative predictive value = 74%, p < 0.0001). Clinical models failed to predict remission status at better than chance levels. Testing the model on the alternative YoDA-A dataset confirmed its ability to predict remission (AUC = 0.776, balanced accuracy = 64%, negative predictive value = 70%, p < 0.0001). Conclusions: We confirm that rACC activity acts as a prognostic biomarker for depression. The machine learning model can identify patients who are likely to have difficult-to-treat depression, which might direct the earlier provision of enhanced support and more intensive therapies. [ABSTRACT FROM AUTHOR]

Objective: Depression is one of the most prevalent and disabling mental health conditions among young people worldwide. The health and economic burdens associated with depressive illness are substantial. Suicide and depression are closely intertwined, yet a diagnosis of depression itself lacks predictive specificity for suicidal behaviour. To better inform suicide prevention and early intervention strategies for young people, improved identification of modifiable intervention targets is needed. The objective of this review was to identify clinical, psychosocial and biological correlates of suicidality in young people diagnosed with a broad range of unipolar and bipolar depressive disorders. Method: Systematic searches were conducted across MEDLINE, Embase and PsycINFO to identify studies of young people aged 15–25 years diagnosed with unipolar or bipolar depressive disorders. An assessment of suicidality was required for inclusion. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Synthesis Without Meta-analysis guidelines. Results: We integrated findings from 71 studies including approximately 24,670 young people with clinically diagnosed depression. We identified 26 clinical, psychosocial and biological correlates of suicidality. Depression characteristics (type and severity), psychiatric comorbidity (particularly anxiety and substance use disorders) and neurological characteristics emerged as having the most evidence for being associated with suicidal outcomes. Our ability to pool data and conduct meaningful quantitative synthesis was hampered by substantial heterogeneity across studies and incomplete reporting; thus, meta-analysis was not possible. Conclusion: Findings of this review reinforce the notion that suicidality is a complex phenomenon arising from the interplay of multiple contributing factors. Our findings question the utility of considering a diagnosis of depression as a specific risk factor for suicidality in young people. Suicidality itself is transdiagnostic; adoption of a transdiagnostic approach to investigating its aetiology and treatment is perhaps warranted. Future research investigating specific symptoms, or symptom networks, might help to further our understanding of suicidality among young people experiencing mental illness. [ABSTRACT FROM AUTHOR]

Self-referential and social processing are often engaged concurrently in naturalistic judgements and elicit activity in overlapping brain regions. We have termed this integrated processing 'self-other referential processing' and developed a task to measure its neural correlates. Ninety-eight healthy young people aged 16–25 (M = 21.5 years old, 67% female) completed our novel functional magnetic resonance imaging task. The task had two conditions, an active self-other referential processing condition in which participants rated how much they related to emotional faces and a control condition. Rating relatedness required thinking about oneself (self-referential processing) and drawing a comparison to an imagined other (social processing). Self-other referential processing elicited activity in the default mode network and social cognition system; most notably in the 'core self' regions of the medial prefrontal cortex and posterior cingulate cortex. Relatedness and emotional valence directly modulated activity in these core self areas, while emotional valence additionally modulated medial prefrontal cortex activity. This shows the key role of the medial prefrontal cortex in constructing the 'social-affective self'. This may help to unify disparate models of medial prefrontal cortex function, demonstrating its role in coordinating multiple processes—self-referential, social and affective processing—to allow the self to exist in a complex social world. [ABSTRACT FROM AUTHOR]

An editorial is presented on ketamine and 3,4-methylenedioxymethamphetamine (MDMA) being old drugs with apparent new uses. Topics include focusing on the brain mechanisms of depression in the role of the glutamatergic system; increasing glutamate transmission having toxic brain effects precipitating and perpetuating depression; and considering chemotherapies for cancers and intravenous immunoglobulin for autoimmune disorders.

Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth. Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention. A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was −5.8 in the n-3 PUFA group and −5.6 in the placebo group (mean difference, 0.2; 95% CI, −1.1 to 1.5; p =.75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups. This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder. [ABSTRACT FROM AUTHOR]

The article discusses the change in the direction of the relationship between clinicians and researchers and the lived experience of people with mental illness. Topics covered include the growing contribution of lived experience in clinical and research practice, the emergence of co-design as an important component of research practice, and the reason behind the less prominence of the lived experiences of researchers and clinicians.

In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato®) for depression. However, Spravato is priced at $600–$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public–private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research. [ABSTRACT FROM AUTHOR]

Objective: A disturbed sense of self is a core feature of depression. The medial prefrontal cortex, which has a central role in self-appraisal processes, is often implicated in the illness, although it remains unclear how functional alterations of the region contribute to the observed disturbances. The aim of this study was to clarify the role of the medial prefrontal cortex in self-appraisal processes in depression.Method: The authors applied a recently developed dynamic network model of self-directed cognition to functional MRI data from 71 adolescents and young adults with moderate to severe major depressive disorder, none of whom were being treated with medication, and 88 healthy control participants. Bayesian model averaging was used to determine parameter estimates for the dynamic causal models, which were compared between groups.Results: While self-directed cognitive processes in the depression group were shown to rely on the same dynamic network as in the healthy control group, the medial prefrontal cortex had a "hyperregulatory" effect on the posterior cingulate cortex in the depressed group, with self-appraisal causing significantly more negative modulation of connectivity between the medial prefrontal cortex and the posterior cingulate cortex than in the control group (odds ratio=0.54, 95% CI=0.38, 0.77). This parameter was significantly inversely related with a depression factor related to poor concentration and inner tension (r=-0.32; 95% CI=-0.51, -0.08).Conclusions: The exaggerated influence of the medial prefrontal cortex on the posterior cingulate cortex in depression is a neural correlate of the disturbed self-appraisal that is characteristic of the illness. [ABSTRACT FROM AUTHOR]

Background: Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania.Methods: We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs' Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders.Results: The social adjustment component of the PAS correlated with the interpersonal relations (rs = -0.46, p<0.001) domain of QLS while the academic adjustment component of the PAS correlated with the vocational functioning domain of QLS (rs =-0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning.Limitations: Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes.Conclusions: Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions. [ABSTRACT FROM AUTHOR]

The cognitive regulation of emotion is impaired in major depressive disorder and has been linked to an imbalance of prefrontal- subcortical brain activity. Despite suggestions that this relationship represents a neurodevelopmental marker of depression, few studies have examined the neural correlates of emotion regulation in depressed youth. We combined a 'cognitive reappraisal' paradigm with functional magnetic resonance imaging to study the neural correlates of emotional regulation in a large sample of non-medicated depressed adolescents and young adults (n=53) and healthy controls (n=64). As compared with healthy controls, young people with depression were less able to reduce negative affect during reappraisal, which corresponded to blunted modulation of amygdala activity. While in healthy individuals amygdala activation was modulated by age, no such relationship was observed in depressed individuals. Heightened activation of the ventromedial pre-frontal cortex (vmPFC) and reduced activation of the dorsal midline cortex was also found for the depressed group. Overall, these findings suggest that brain systems that support cognitive reappraisal are functionally altered in youth depression. We argue that excessive engagement of the vmPFC in particular, may be central to understanding how the process of putting a 'positive spin' on negative emotional material may be altered in depressed youth. [ABSTRACT FROM AUTHOR]

Major depression is a debilitating condition characterised by diverse neurocognitive and behavioural deficits. Nevertheless, our species-typical capacity for depressed mood implies that it serves an adaptive function. Here we apply an interdisciplinary theory of brain function to explain depressed mood and its clinical manifestations. Combining insights from the free-energy principle (FEP) with evolutionary theorising in psychology, we argue that depression reflects an adaptive response to perceived threats of aversive social outcomes (e.g., exclusion) that minimises the likelihood of surprising interpersonal exchanges (i.e., those with unpredictable outcomes). We suggest that psychopathology typically arises from ineffectual attempts to alleviate interpersonal difficulties and/or hyper-reactive neurobiological responses to social stress (i.e., uncertainty), which often stems from early experience that social uncertainty is difficult to resolve. [ABSTRACT FROM AUTHOR]

The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants, we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified ‘core-self’ DMN regions—in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule—using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes and extend our understanding of their functionally specialized roles. [ABSTRACT FROM AUTHOR]

Few studies have examined the neural correlates of emotion regulation across adolescence and young adulthood. Existing studies of cognitive reappraisal indicate that improvements in regulatory efficiency may develop linearly across this period, in accordance with maturation of prefrontal cortical systems. However, there is also evidence for adolescent differences in reappraisal specific to the activation of "social-information processing network" regions, including the amygdala and temporal-occipital cortices. Here, we use fMRI to examine the neural correlates of emotional reactivity and reappraisal in response to aversive social imagery in a group of 78 adolescents and young adults aged 15-25 years. Within the group, younger participants exhibited greater activation of temporal-occipital brain regions during reappraisal in combination with weaker suppression of amygdala reactivity-the latter being a general correlate of successful reappraisal. Further analyses demonstrated that these age-related influences on amygdala reactivity were specifically mediated by activation of the fusiform face area. Overall, these findings suggest that enhanced processing of salient social cues (i.e., faces) increases reactivity of the amygdala during reappraisal and that this relationship is stronger in younger adolescents. How these relationships contribute to well-known vulnerabilities of emotion regulation during this developmental period will be an important topic for ongoing research. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses about the articles in the issues including challenges faced by psychiatry, scope and role of psychiatry, and biological versus social reductionism.

Background: The aim of the Youth Depression Alleviation–Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support. Methods/Design: YoDA-C is a double-blind, randomised controlled trial funded by the Australian government’s National Health and Medical Research Council. Participants between the ages of 15 and 25 years with moderate to severe major depressive disorder will be randomised to receive either (1) cognitive behavioural therapy (CBT) and fluoxetine or (2) CBT and placebo. The treatment duration will be 12 weeks, and follow-up will be conducted at 26 weeks. The primary outcome measure is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after 12 weeks of treatment. The MADRS will be administered at baseline and at weeks 4, 8, 12 and 26. Secondary outcome measures will address additional clinical outcomes, functioning, quality of life and safety. [ABSTRACT FROM AUTHOR]

The 'core' regions of the default mode network (DMN) – the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) – show consistent engagement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswered question. In the current functional magnetic resonance imaging (fMRI) study, we examined dynamic interactions of the 'core-self' DMN regions during two forms of self-referential cognition: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about oneself from a third-person perspective). One-hundred and eleven participants completed our dual self-appraisal task during fMRI, and general linear models were used to characterize common and distinct neural responses to these conditions. Informed by these results, we then applied dynamic causal modelling to examine causal interactions among the 'core-self' regions, and how they were specifically modulated under the influence of direct and reflected self-appraisal. As a primary observation, this network modelling revealed a distinct inhibitory influence of the left IPL on the PCC during reflected compared to direct self-appraisal, which was accompanied by evidence of greater activation in both regions during the reflected self-appraisal condition. We suggest that the greater engagement of posterior DMN regions during reflected self-appraisal is a function of the higher-order processing needed for this form of self-appraisal, with the left IPL supporting abstract self-related processes including episodic memory retrieval and shifts of perspective. Overall, we show that core DMN regions interact in functionally unique ways in support of self-referential processes, even when these processes are inter-related. Further characterization of DMN functional interactions across self-related mental states is likely to inform a deeper understanding of how this brain network orchestrates the self. [ABSTRACT FROM AUTHOR]

Background: Studies of depressed patients have demonstrated increased amygdala activation to negative affective stimuli. In this study, we used a paradigm that employed personally relevant social stimuli, which are known to strongly activate the amygdala, to test whether the amygdala demonstrated aberrant activity in depressed participants as they responded to stimuli with positive valence. Methods: Nineteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. They completed a novel functional magnetic resonance imaging task in which they received social feedback from people who they believed had evaluated them. Voxelwise statistical parametric maps of brain response to positive social feedback and to a control feedback condition were compared to test the hypothesis that differences in neural response between depressed and control participants would arise in the amygdala. Results: Depressed participants showed increased neural response to the positive- versus control-feedback condition in the amygdala (p < .05, corrected). An exploratory analysis showed that depressed participants responded to faces from both feedback conditions with increased activity in regions subserving social appraisal (ventrolateral prefrontal cortex and inferior parietal cortex) and affective processing (pregenual anterior cingulate cortex and anterior insular cortex; p < .001, uncorrected). Conclusions: Depressed patients responded to positive social feedback with increased amygdala activation, demonstrating that amygdala hyperresponsivity in depression is not restricted to negatively-valenced stimuli. The heightened sensitivity of depressed participants to social evaluation may help explain symptoms of depression such as social withdrawal. [Copyright &y& Elsevier]

The experience of being liked is a key social event and fundamental to motivating human behavior, though little is known about its neural underpinnings. In this study, we examined the experience of being liked in a group of 15- to 24-year-old: a cohort for whom forming friendships has a great degree of salience, and for whom the explicit representation of relationships is familiar from their frequent use of social networking technologies. Study participants ( n = 19) were led to believe that other participants had formed an opinion on their likability based on their appearance in a photograph, and during fMRI scanning viewed the photographs of people who had purportedly responded favorably to them (alongside photographs of control participants). Results indicated that being liked activated primary reward- and self-related regions, including the nucleus accumbens, midbrain (in an area corresponding to the ventral tegmentum), ventromedial prefrontal cortex, posterior cingulate cortex (including retrosplenial cortex), amygdala, and insula/opercular cortex. Participants showed greater activation of ventromedial prefrontal cortex and amygdala in response to being liked by people that they regarded highly compared to those they regarded less so. Finally, being liked by the opposite compared to the same gender activated the right caudal orbitofrontal cortex and right anterior insula: areas important for the representation of primary somatic rewards. This study demonstrates that neural response to being liked has features that are consistent with response to other rewarding events, but it has additional features that reflect its intrinsically interpersonal character. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined the neural mediators of trial-by-trial skin conductance responses (SCR), and subjective reports of anxious arousal and valence in participants (n = 27; 17 females) performing a threat reversal task during ultra-high field functional magnetic resonance imaging. This allowed us to identify brain mediators during initial threat learning and subsequent threat reversal. Significant neural mediators of anxious arousal during threat learning included the dorsal anterior cingulate, anterior insula cortex (AIC), and ventromedial prefrontal cortex (vmPFC), subcortical regions including the amygdala, ventral striatum, caudate and putamen, and brain-stem regions including the pons and midbrain. By comparison, autonomic changes (SCR) were mediated by a subset of regions embedded within this broader circuitry that included the caudate, putamen and thalamus, and two distinct clusters within the vmPFC. The neural mediators of subjective negative valence showed prominent effects in posterior cortical regions and, with the exception of the AIC, did not overlap with threat learning task effects. During threat reversal, positive mediators of both subjective anxious arousal and valence mapped to the default mode network; this included the vmPFC, posterior cingulate, temporoparietal junction, and angular gyrus. Decreased SCR during threat reversal was positively mediated by regions including the mid cingulate, AIC, two sub-regions of vmPFC, the thalamus, and the hippocampus. Our findings add novel evidence to support distinct underlying neural processes facilitating autonomic and subjective responding during threat learning and threat reversal. The results suggest that the brain systems engaged in threat learning mostly capture the subjective (anxious arousal) nature of the learning process, and that appropriate responding during threat reversal is facilitated by participants engaging self- and valence-based processes. Autonomic changes (SCR) appear to involve distinct facilitatory and regulatory contributions of vmPFC sub-regions. [ABSTRACT FROM AUTHOR]

Abstract: Adolescent development is accompanied by the emergence of a population-wide increase in vulnerability to depression that is maintained through adulthood. We provide a model for understanding how this vulnerability to depression arises, and why depression is so often precipitated by social rejection or loss of status during this phase. There is substantial remodeling and maturation of the dopaminergic reward system and the prefrontal cortex during adolescence, that coincides with the adolescent entering the complex world of adult peer and romantic relationships, where the rewards that can be obtained (feelings such as belonging, romantic love, status and agency) are abstract and temporally distant from the proximal context. Development of the prefrontal cortex makes it possible to pursue such complex and distal rewards, which are, however, tenuous and more readily frustrated than more immediate rewards. We hypothesize that when these distant rewards are frustrated they suppress the reward system, and that when such suppression is extensive and occurs for long enough, the clinical picture that results is one of depression. [Copyright &y& Elsevier]

The article discusses the use of cannabis and its components, particularly delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), for various medical conditions, including psychiatric disorders.Topics include the use of cannabis and its components for medical purposes; the differences between THC and CBD in terms of psychoactive effects, and the need for more research, particularly randomized controlled trials, to assess the effectiveness and safety of CBD for psychiatric disorders.

Background: Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences. Therefore, we specifically investigated sex-specific effects on the interaction between emotionally induced changes in physiology and behavioral performance on a decision-making task. Methods: Skin conductance responses of twenty-nine adults with ADHD (n = 16 male; n = 13 female) and thirty-three adults in the control group (n = 14 male; n = 19 female) were recorded during the performance in a modified version of the Balloon Analogue Risk Task (BART). Additional questionnaires were used to reveal insights in the self-assessment of emotional competence, risk perception, and feedback sensitivity. Emotional arousal and decision-making behavior were analyzed using linear mixed-effects models. Results: Results showed different effects of sex on risk behaviors in controls and ADHD. In contrast to healthy controls, female adults with ADHD showed a significantly greater risk engagement in the BART compared to males with ADHD. This contrary sex relation was not observed in skin conductance responses and revealed a significantly different sex-dependent correlation of body response and behavioral task performance in ADHD. Comparisons with results from self-assessments furthermore indicate a reduced behavioral self-perception in women with ADHD, but not in men. Conclusion: In summary, we found an altered interaction between physiological activity and risky behavior in women with ADHD. Thus, the present study indicates a reduced sensitivity towards the own bodily responses in women with ADHD, which could consequently cause increased risky DM behavior in daily life. The current results suggest that more consideration needs to be given to sex-specific effects on physiological processes and behavior in adults with ADHD. [ABSTRACT FROM AUTHOR]

• Social anxiety disorder (SAD) has been linked to impaired fear regulation. • We investigated threat and safety reversal learning in young patients with SAD. • People with SAD showed unimpaired reversal learning across all measured domains. • Overall, higher social anxiety symptoms predicted more safety reversal learning. Social anxiety disorder (SAD) has been linked to maladaptive forms of fear regulation, including flexibly distinguishing between learned threat and safety signals. Few studies have examined this in young, unmedicated SAD patients, including its neural basis. We aimed to characterize the neural, subjective, and autonomic correlates of reversal learning in patients with SAD and compare them to matched patients with major depressive disorder and to healthy control participants. All participants completed a threat-safety reversal learning task during functional magnetic resonance imaging. Successful threat-safety updating was associated with significant activation of primary regions of interest (anterior cingulate, insula and ventromedial prefrontal cortex), however, no significant differences were observed between them, consistent with subjective reports of task-evoked anxiety and affect. Contrary to expectations, we did not observe threat and safety reversal learning to be significantly impaired in young people with SAD. [ABSTRACT FROM AUTHOR]

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (7 Tesla) fMRI to examine the neural basis of safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation (PFDR whole-brain corrected). The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular, and dorsolateral PFC compared with the standard safety signal, whereas the latter evoked greater activation of the ventromedial PFC, posterior cingulate, and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, mid-brain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS ). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of "stimulus-safety" associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning. [ABSTRACT FROM AUTHOR]

Responding flexibly to sources of threat and safety is critical to the adaptive regulation of emotions, including fear. At a neural systems level, such flexibility is thought to rely on an extended neural circuitry involving the dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortices (vmPFC), although precisely how this occurs remains unclear. Using a novel fear reversal task and functional magnetic resonance imaging (fMRI), we examined the neural correlates of threat and safety reversal learning and their associations with individual differences in anxious responding in a large sample of healthy adolescents and young adults. Overall, participants demonstrated successful threat and safety reversal learning, as indexed by subjective ratings. At a whole-brain level, threat reversal was associated with significant activation of the bilateral anterior insular cortex and dACC, in particular its rostral subregion. Conversely, safety reversal led to significant activation of the anterior vmPFC, together with posterior mid-line regions. Further analyses of regional responses suggested a more selective role for the rostral dACC in threat signal updating, as well as a direct association of its activity with participants' change in subjective anxious arousal to the reversed threat. Taken together, our findings complement existing neurocircuitry models of human fear regulation, particularly regarding the importance of midline cortical regions, and provide further insights into their specific contribution to flexible threat-safety signal processing. In particular, our results suggest that rostral dACC function may be more centrally involved in regulating levels of anxious arousal when flexibility is required. They also raise important questions regarding the vmPFC's role in safety learning, particularly involving its hypothesized subregional contributions to response inhibitory versus stimulus value processing functions. • Examined functional correlates of threat and safety reversal learning in large healthy cohort. • Investigated associations with individual differences in anxious arousal. • Key role for cortical midline regions in responding flexibly to reversed threat and safety signals. • A role for the dorsal anterior cingulate cortex in threat signal updating and subjective anxiety. • Address ventromedial prefrontal cortex subregional specificity in safety reversal learning. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to analyze the real‐time variability of suicidal ideation intensity and the relationship between real‐time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). Methods: Young people (15–25‐year olds) with BPD (N = 46), recruited from two government‐funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. Results: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real‐time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. Conclusion: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week. [ABSTRACT FROM AUTHOR]

Background: Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response. Methods: Ninety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders. Results: Depressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing. Conclusions: Our study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response. [ABSTRACT FROM AUTHOR]

We provide a proof of principle for an evolutionary systems theory (EST) of depression. This theory suggests that normative depressive symptoms counter socioenvironmental volatility by increasing interpersonal support via social signalling and that this response depends upon the encoding of uncertainty about social contingencies, which can be targeted by neuromodulatory antidepressants. We simulated agents that committed to a series of decisions in a social two-arm bandit task before and after social adversity, which precipitated depressive symptoms. Responses to social adversity were modelled under various combinations of social support and pharmacotherapy. The normative depressive phenotype responded positively to social support and simulated treatments with antidepressants. Attracting social support and administering antidepressants also alleviated anhedonia and social withdrawal, speaking to improvements in interpersonal relationships. These results support the EST of depression by demonstrating that following adversity, normative depressed mood preserved social inclusion with appropriate interpersonal support or pharmacotherapy. [ABSTRACT FROM AUTHOR]

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self‐disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12‐month follow‐up. Methods: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. Results: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. Conclusions: The SNAP study will test whether neurophenomenological disturbances associated with basic self‐disturbance predict persistence or intensification of UHR symptomatology over a 2‐year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis. [ABSTRACT FROM AUTHOR]

Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults. We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint. No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was −4.58 (95 % CI, −6.59 to −2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment. There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies. There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed. • Absence of trials for use of antipsychotics to treat youth unipolar depression • Limited evidence for use of atypical antipsychotics in youth bipolar depression • Quetiapine not shown to be effective • Lurasidone and Olanzapine/fluoxetine combination some evidence for efficacy • More studies required on a wider range of antipsychotics [ABSTRACT FROM AUTHOR]

There is an urgent need for rapidly acting antidepressants. Current therapies share a delayed onset of action, contrasting with drugs of abuse that have rapid psychotropic effects but cause tolerance and dependence. A key uncertainty is whether there is a finite speed limit imposed by the critical role of homeostatic adaptive mechanisms that underpin the efficacy and onset of available psychotropic agents and whether this is mutable with emerging agents with potential rapid onset, in particular ketamine. [ABSTRACT FROM AUTHOR]

Abstract: Aim: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well‐documented, anti‐inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti‐inflammatory agent (YoDA‐A) study is to determine whether individuals receiving adjunctive anti‐inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. Methods: YoDA‐A is a 12‐week triple‐blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15–25, with moderate‐to‐severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to week 12. Results: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. Conclusion: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and ‘real‐world’, but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD. [ABSTRACT FROM AUTHOR]

Introduction: Psychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis.Methods: Among a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments.Results: Eighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning.Discussion: In addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase. [ABSTRACT FROM AUTHOR]

Objective: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. Methods: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15–25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. Results: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. Conclusions: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression. [ABSTRACT FROM AUTHOR]

This systematic review aimed to provide a comprehensive summary of the current literature on the neurobiological underpinnings of the experience of the negative moral emotions: shame, embarrassment and guilt. PsycINFO, PubMed and MEDLINE were used to identify existing studies. Twenty-one functional and structural magnetic resonance imaging and positron emission tomography studies were reviewed. Although studies differed considerably in methodology, their findings highlight both shared and distinct patterns of brain structure/function associated with these emotions. Shame was more likely to be associated with activity in the dorsolateral prefrontal cortex, posterior cingulate cortex and sensorimotor cortex; embarrassment was more likely to be associated with activity in the ventrolateral prefrontal cortex and amygdala; guilt was more likely to be associated with activity in ventral anterior cingulate cortex, posterior temporal regions and the precuneus. Although results point to some common and some distinct neural underpinnings of these emotions, further research is required to replicate findings. [ABSTRACT FROM AUTHOR]

Aim: Major depressive disorder (MDD) has far reaching impacts for young people, their families and society. Cognitive behavioural therapy (CBT) is one of the first‐line treatments for young people experiencing MDD; however, there is limited research examining how young people with MDD experience CBT. The aim of this study was to explore their experience and their views of this intervention. Methods: We employed a qualitative research design, with semi‐structured interviews and thematic analysis. Eight participants aged between 17 and 24 years who received CBT for MDD in a randomized controlled trial were recruited. Results: Five themes were identified: the importance of relationship with clinician; the range of useful components within CBT; the ability for CBT to accommodate different techniques and presenting issues; the importance of checking in with clients during the process of therapy; and the impacts of MDD on therapy. Conclusions: The findings highlight the importance of clinicians having a youth friendly and collaborative approach that allows a modular delivery of a range of CBT techniques to suit the client's presenting issue and formulation. There is a need to continually check how young people are responding to interventions, and to be aware of potential cognitive deficits and adjust therapy accordingly. This is a small study that provides insight into how young people with MDD experience CBT and avenues to explore for tailoring provision of CBT to enhance the therapeutic experience for this population. [ABSTRACT FROM AUTHOR]

Safety learning creates associations between conditional stimuli and the absence of threat. Studies of human fear conditioning have accumulated evidence for the neural signatures of safety over various paradigms, aligning on several common brain systems. While these systems are often interpreted as underlying safety learning in a generic sense, they may instead reflect the expression of learned safety, pertaining to processes of fear inhibition, positive affect, and memory. Animal models strongly suggest these can be separable from neural circuits implicated in the conditioning process itself (or safety acquisition). While acquisition-expression distinctions are ubiquitous in behavioural science, this lens has not been applied to safety learning, which remains a novel area in the field. In this mini-review, we overview findings from prevalent safety paradigms in humans, and synthesise these with insights from animal models to propose that the neurobiology of safety learning be conceptualised along an acquisition-expression model, with the aim of stimulating richer brain-based characterisations of this important process. [ABSTRACT FROM AUTHOR]

Background Identification of earlier stages of Bipolar Disorder (BD), even prior to the first manic episode, may help develop interventions to prevent or delay the onset of BD. However, reliable and valid instruments are necessary to ascertain such earlier stages of BD. The aim of the current review was to identify instruments that had predictive validity and utility for BD for use in early intervention (EI) settings for the prevention of BD. Methods We undertook a systematic examination of studies that examined participants without BD I or II at baseline and prospectively explored the predictive abilities of instruments for BD onset over a period of 6 months or more. The instruments and the studies were rated with respect to their relative validity and utility predicting onset of BD for prevention or early intervention. Odds ratios and area under the curve (AUC) values were derived when not reported. Results Six studies were included, identifying five instruments that examined sub-threshold symptoms, family history, temperament and behavioral regulation. Though none of the identified instruments had been examined in high-quality replicated studies for predicting BD, two instruments, namely the Child Behavioral Checklist – Pediatric BD phenotype (CBCL-PBD) and the General Behavioral Inventory – Revised (GBI-R), had greater levels of validity and utility. Limitation Non-inclusion of studies and instruments that incidentally identified BD on follow-up limited the breadth of the review. Conclusion Instruments that test domains such as subthreshold symptoms, behavioral regulation, family history, and temperament hold promise in predicting BD onset. [ABSTRACT FROM AUTHOR]

Aim: The concept of severe and complex youth depression has evolved from clinical experience. Here we conducted a file audit study to evaluate supporting data for the construct. Methods: A retrospective file audit was undertaken with 84 consecutively discharged patients over 6‐months from Orygen's Youth Mood Clinic (YMC; 50% female). Results: Over a third (36.9%) were disengaged from vocation and education, with exposure to traumatic events common (84.5%). Almost all patients (91.7%) reported past 2‐week suicidal ideation at clinic entry. Hospital emergency departments were the most frequent referral source (31.0%). Most (72.6%) had received previous mental health treatment. Multimorbidity was frequently observed. The presence of a substance use disorder, or ≥ 3 comorbidities were both associated with a greater likelihood of prior suicide attempt. Conclusions: These data highlight the clinical needs associated with severe and complex depression. Findings have implications for youth experiencing mood disorders attending tertiary and community mental health settings. [ABSTRACT FROM AUTHOR]

A correction for the article "Altered effective connectivity of the extended face processing system in depression and its association with treatment response: findings from the YoDA-C randomized controlled trial" is presented, which is publiehed in the July 21, 2021 issue of the periodical.

Background: People with depression often present with concurrent cognitive impairment. Computerized cognitive training (CCT) is a safe and efficacious strategy to maintain or enhance cognitive performance in a range of clinical populations. However, its efficacy in people with depression and how it varies across populations and design factors are currently unclear. Methods: We searched MEDLINE, EMBASE, and PsycINFO from inception to 13 July 2021 for randomised controlled trials examining the efficacy of CCT vs any control condition on cognitive, mood, psychiatric symptoms, psychosocial, and daily functioning in adults with depression. Eligible samples include studies specifically targeting people with major depressive disorder as well as those with other diagnoses where at least 50% of the sample meets the clinical criteria for depression, with the exception of major psychiatric disorders or dementia. The primary outcome is change in the overall cognitive performance. Multivariate analyses will be used to examine the effect sizes on each outcome category as well as possible effect modifiers and correlations between categories. The risk of bias will be assessed using the Cochrane risk of bias tool version 2. Discussion: To the best of our knowledge, this will be the first systematic review and meta-analysis of narrowly defined CCT across clinical populations with depression. We aim to investigate not only whether CCT is efficacious for cognition, but also how such effects vary across design factors, what other clinically relevant outcomes might respond to CCT, and the extent to which they differ across populations. Systematic review registration: PROSPERO CRD42020204209 [ABSTRACT FROM AUTHOR]

Objective: The increasing focus on adolescent personality disorder has tended to ignore evidence of the developmental continuity of the period from puberty to young adulthood. This study aims to: (1) describe the characteristics of a sample of young people with borderline personality disorder (BPD) who had no previous history of evidence-based treatment for the disorder and (2) compare their characteristics by participant age group. Methods: One hundred and thirty-nine young people (15 to 25 years) with BPD, newly enrolled in the Monitoring Outcomes of BPD in Youth randomized controlled trial, completed semi-structured interview and self-report measures assessing demographic, clinical, and functional characteristics. Younger (aged 15 to 17 years; n = 64) and older (aged 18 to 25 years; n = 75) participants were compared on these same variables using t -tests, chi-square tests, and logistic regression. Results: Young outpatients with BPD had extensive and severe psychopathology and were functioning poorly. Adolescents and young adults with BPD showed substantial similarities on 20 key aspects of their presentation. Significant between-groups differences were observed in household makeup, treatment history, antisocial personality disorder, emotion dysregulation, substance use, age of commencement and extent of self-harm, and achievement of age-appropriate educational milestones. Adolescent BPD group membership was predicted by family composition and self-harm, whereas young adult BPD group membership was predicted by not achieving age-appropriate milestones, vocational disengagement, and emotion dysregulation. The final model explained 54% of the variance and correctly classified 80.2% of the sample by age. Conclusions: Both adolescents and young adults with early stage BPD present with severe and often similar problems to one another, supporting developmental continuity across this age range. However, there are also meaningful differences in presentation, suggesting that pathways to care might differ by age and/or developmental stage. Detection and intervention for personality disorder should not be delayed until individuals reach 18 years of age. [ABSTRACT FROM AUTHOR]