[Detection and management of patients with clinical high risk for psychosis]. / Détection et prise en charge des patients avec états mentaux à risque de psychose.

This article explores best practices for managing patients with Clinical High Risk for psychosis with a particular focus on the role of general practitioners and pediatricians. It offers clear guidelines for the assessment and monitoring of these patients, highlighting early warning signs, screening tools, and appropriate interventions. Additionally, the article lists local resources available for healthcare professionals to ensure optimal and coordinated care. By providing this information, this article aims to equip general practitioners and pediatricians with the necessary knowledge to effectively identify and manage this patient profile, while connecting them to the appropriate available resources.

Cet article explore les meilleures pratiques pour la prise en charge des états mentaux à risque de psychose avec un accent particulier sur le rôle des généralistes et des pédiatres. Il propose des directives claires pour l'évaluation et le suivi de ces patients, en mettant en lumière les premiers signes avant-coureurs, les outils de dépistage et les interventions appropriées. En outre, l'article recense les ressources locales disponibles pour les professionnels de santé, afin d'assurer une prise en charge optimale et coordonnée. En fournissant ces informations, il vise à mieux armer les généralistes et pédiatres des connaissances nécessaires pour identifier et gérer efficacement ces patients, tout en les connectant aux ressources adéquates disponibles.

[Impact of social determinants on mental disorders in adolescents and young adults]. / Impact des déterminants sociaux sur les troubles psychiques des adolescents et jeunes adultes.

The impact of social determinants on mental disorders of adolescents and young adults has been amplified by the Covid-19 pandemic and its consequences. To raise clinicians' awareness of these effects in practice, this article examines two particularly well-studied areas: the effects of socioeconomic disadvantages on emerging psychotic disorders and the impact of gender on depression. In clinical practice it is crucial to consider social stress factors, confronting young people in an unequal manner, as they contribute to the emergence or relapse of mental disorders. Two illustrations of the potential impacts of social determinants on the mental health of adolescents and young adults are presented, as well as intervention strategies for practitioners.

L'impact des déterminants sociaux sur les troubles psychiques des adolescents et des jeunes adultes a été amplifié par la pandémie de Covid-19 et ses conséquences économiques et sociales. Afin de sensibiliser les cliniciens à leurs effets dans la pratique, cet article présente deux domaines particulièrement étudiés : les effets des désavantages socioéconomiques sur l'émergence des troubles psychotiques et ceux du genre sur la dépression. Dans la pratique clinique, il est crucial de prendre en compte ces facteurs de stress sociaux, auxquels les jeunes sont confrontés de manière inégale, car ils contribuent à l'émergence ou à la rechute de leurs troubles psychiques. Deux illustrations de l'impact potentiel des déterminants sociaux sur la santé mentale des adolescents et des jeunes adultes sont proposées, ainsi que des pistes d'interventions pour les praticiens.

MULTIMODAL NEURAL CORRELATES OF CHILDHOOD PSYCHOPATHOLOGY.

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

Hippocampal temporal dynamics and spatial heterogeneity unveil vulnerability markers in the offspring of bipolar patients.

OBJECTIVES: Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups. METHODS: We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (µCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). µCAPs allow a data-driven differentiation within the seed region. RESULTS: dFC between the hippocampal body and a somatomotor-µCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-µCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-µCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02). CONCLUSION: Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.

Transdiagnostic markers across the psychosis continuum: a systematic review and meta-analysis of resting state fMRI studies.

Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).

Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder.

Amygdala functional dysconnectivity lies at the heart of the pathophysiology of bipolar disorder (BD). Recent preclinical studies suggest that the amygdala is a heterogeneous group of nuclei, whose specific connectivity could drive positive or negative emotional valence. We investigated functional connectivity (FC) changes within these circuits emerging from each amygdala's subdivision in 127 patients with BD in different mood states and 131 healthy controls (HC), who underwent resting-state functional MRI. FC was evaluated between lateral and medial nuclei of amygdalae, and key subcortical regions of the emotion processing network: anterior and posterior parts of the hippocampus, and core and shell parts of the nucleus accumbens. FC was compared across groups, and subgroups of patients depending on their mood states, using linear mixed models. We also tested correlations between FC and depression (MADRS) and mania (YMRS) scores. We found no difference between the whole sample of BD patients vs. HC but a significant correlation between MADRS and right lateral amygdala /right anterior hippocampus, right lateral amygdala/right posterior hippocampus and right lateral amygdala/left anterior hippocampus FC (r = -0.44, r = -0.32, r = -0.27, respectively, all pFDR<0.05). Subgroup analysis revealed decreased right lateral amygdala/right anterior hippocampus and right lateral amygdala/right posterior hippocampus FC in depressed vs. non-depressed patients and increased left medial amygdala/shell part of the left nucleus accumbens FC in manic vs non-manic patients. These results demonstrate that acute mood states in BD concur with FC changes in individual nuclei of the amygdala implicated in distinct emotional valence processing. Overall, our data highlight the importance to consider the amygdala subnuclei separately when studying its FC patterns including patients in distinct homogeneous mood states.

[Early interventions for emotional regulation in adolescence, where are we?] / Interventions précoces pour la régulation émotionnelle à l'adolescence.

Adolescence is a vulnerable period for mental health. It is not easy to make a precise diagnosis during this period, as young people may present attenuated forms of psychiatric pathology, or on the contrary, a combination of several types of difficulties. Adopting a transdiagnostic and dimensional approach, based on clinical stages, and thus proposing interventions adapted to the severity of symptoms, is pertinent. As emotional dysregulation lies at the heart of many pathologies, it is a prime target for early intervention. Although interventions for adolescents are still underdeveloped, certain approaches derived from cognitive-behavioral therapies and the psychodynamic current have been adapted for adolescents and appear promising.

L'adolescence constitue une période vulnérable pour la santé mentale. Poser un diagnostic précis durant cette période n'est pas aisé car les jeunes peuvent présenter des formes atténuées de pathologies psychiatriques, ou, au contraire, une combinaison de plusieurs types de difficultés. Adopter une approche transdiagnostique et dimensionnelle, en fonction de stades cliniques, et ainsi proposer des interventions adaptées à la sévérité des symptômes est pertinent. La dysrégulation émotionnelle étant au cœur de nombreuses pathologies, elle est une cible de premier choix pour des interventions précoces. Bien que les interventions pour les adolescents soient encore peu développées, certaines approches issues des thérapies cognitivo-comportementales et du courant psychodynamique ont été adaptées pour les adolescents et semblent prometteuses.

Interventions targeting emotion regulation: A systematic umbrella review.

BACKGROUND: Emotion dysregulation (ED), the difficulty in modulating which emotions are felt, and when and how they are expressed or experienced, has been implicated in an array of psychological disorders. Despite potentially different manifestations depending on the disorder, this symptom is emerging as a transdiagnostic construct that can and should be targeted early, given the associations with various maladaptive behaviors as early as childhood and adolescence. As such, our goal was to investigate the psychotherapeutic interventions used to address ED and gauge their effectiveness, safety, and potential mechanisms across various populations. METHODS: This umbrella systematic review, pre-registered under PROSPERO (registration: CRD42023411452), consolidates evidence from systematic reviews and meta-analyses on psychotherapeutic interventions targeting ED, in accordance with PRISMA guidelines. RESULTS: Our synthesis of quantitative and qualitative evidence from 21 systematic reviews (including 11 meta-analyses) points-with moderate overall risk of bias-to the effectiveness of Dialectical Behavior Therapy and Cognitive Behavioral Therapy in reducing ED in a wide range of adult transdiagnostic psychiatric patients and healthy participants. Similar results have emerged in other less extensively researched methods as well. However, results on adolescents and children are sparse, highlighting the need for additional research to tailor these interventions to the unique challenges of ED in younger populations with diverse externalizing and internalizing disorders. CONCLUSIONS: These demonstrated transdiagnostic advantages of psychotherapy for ED underscore the potential for specifically designed interventions that address this issue directly, particularly for high-risk individuals. In these individuals, early interventions targeting transdiagnostic core dimensions may mitigate the emergence of full-blown disorders. Future research on the mediating factors, the durability of intervention effects, and the exploration of understudied interventions and populations may enhance prevention and treatment efficiency, enhancing the quality of life for those affected by varied manifestations of ED.

Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents.

Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13-15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Resting-State EEG Microstates and Power Spectrum in Borderline Personality Disorder: A High-Density EEG Study.

Borderline personality disorder (BPD) is a debilitating psychiatric condition characterized by emotional dysregulation, unstable sense of self, and impulsive, potentially self-harming behavior. In order to provide new neurophysiological insights on BPD, we complemented resting-state EEG frequency spectrum analysis with EEG microstates (MS) analysis to capture the spatiotemporal dynamics of large-scale neural networks. High-density EEG was recorded at rest in 16 BPD patients and 16 age-matched neurotypical controls. The relative power spectrum and broadband MS spatiotemporal parameters were compared between groups and their inter-correlations were examined. Compared to controls, BPD patients showed similar global spectral power, but exploratory univariate analyses on single channels indicated reduced relative alpha power and enhanced relative delta power at parietal electrodes. In terms of EEG MS, BPD patients displayed similar MS topographies as controls, indicating comparable neural generators. However, the MS temporal dynamics were significantly altered in BPD patients, who demonstrated opposite prevalence of MS C (lower than controls) and MS E (higher than controls). Interestingly, MS C prevalence correlated positively with global alpha power and negatively with global delta power, while MS E did not correlate with any measures of spectral power. Taken together, these observations suggest that BPD patients exhibit a state of cortical hyperactivation, represented by decreased posterior alpha power, together with an elevated presence of MS E, consistent with symptoms of elevated arousal and/or vigilance. This is the first study to investigate resting-state MS patterns in BPD, with findings of elevated MS E and the suggestion of reduced posterior alpha power indicating a disorder-specific neurophysiological signature previously unreported in a psychiatric population.

Dynamic functional hippocampal markers of residual depressive symptoms in euthymic bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. METHODS: We assessed hippocampus-based dFC coactivation patterns (CAPs) on resting-state fMRI data of 25 euthymic BD patients and 25 age- and sex-matched healthy controls (HC). RESULTS: Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo-insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default-like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. CONCLUSIONS: Overall, we observed alterations of large-scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self-centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow-up of BD patients and of disabling residual depressive symptoms in particular.

Neural Basis of Internal Attention in Adults with Pure and Comorbid ADHD.

OBJECTIVE: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. METHODS: We used a word processing paradigm to assess neural activations in adults with ADHD (N = 46) compared to controls (N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD (N = 18). RESULTS: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. CONCLUSION: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.

Structural and functional MRI correlates of inflammation in bipolar disorder: A systematic review.

BACKGROUND: Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI abnormalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. METHODS: In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. RESULTS: We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1'233 BD patients). Overall, the quality of the studies included was fair, with a low risk of bias. LIMITATIONS: Heterogeneity in the methods and results of the studies and small sample sizes limit the generalizability of the conclusions. CONCLUSIONS: A qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.

Global and local cortical folding alterations are associated with neurodevelopmental subtype in bipolar disorders: a sulcal pits analysis.

BACKGROUND: Analyzing cortical folding may provide insight into the biological underpinnings of neurodevelopmental diseases. A neurodevelopmental subtype of bipolar disorders (BD-ND) has been characterized by the combination of early age of onset and psychotic features. We investigate potential cortical morphology differences associated with this subtype. We analyze, for the first time in bipolar disorders, the sulcal pits, the deepest points in each fold of the cerebral cortex. METHODS: We extracted the sulcal pits from anatomical MRI among 512 participants gathered from 7 scanning sites. We compared the number of sulcal pits in each hemisphere as well as their regional occurrence and depth between the BD-ND subgroup (N = 184), a subgroup without neurodevelopmental features (BD, N = 77) and a group of healthy controls (HC, N = 251). RESULTS: In whole brain analysis, BD-ND group have a higher number of sulcal pits in comparison to the BD group. The local analysis revealed, after correction for multiple testing, a higher occurrence of sulcal pits in the left premotor cortex among the BD-ND subgroup compared to the BD and the HC groups. CONCLUSION: Our findings confirm that BD-ND is associated with a specific brain morphology revealed by the analysis of sulcal pits. These markers may help to better understand neurodevelopment in mood disorder and stratify patients according to a pathophysiological hypothesis.

Real-time fMRI neurofeedback as a new treatment for psychiatric disorders: A meta-analysis.

Neurofeedback using real-time functional MRI (RT-fMRI-NF) is an innovative technique that allows to voluntarily modulate a targeted brain response and its associated behavior. Despite promising results in the current literature, its effectiveness on symptoms management in psychiatric disorders is not yet clearly demonstrated. Here, we provide 1) a state-of-art qualitative review of RT-fMRI-NF studies aiming at alleviating clinical symptoms in a psychiatric population; 2) a quantitative evaluation (meta-analysis) of RT-fMRI-NF effectiveness on various psychiatric disorders and 3) methodological suggestions for future studies. Thirty-one clinical trials focusing on psychiatric disorders were included and categorized according to standard diagnostic categories. Among the 31 identified studies, 22 consisted of controlled trials, of which only eight showed significant clinical improvement in the experimental vs. control group after the training. Nine studies found an effect at follow-up on ADHD symptoms, emotion dysregulation, facial emotion processing, depressive symptoms, hallucinations, psychotic symptoms, and specific phobia. Within-group meta-analysis revealed large effects of the NF training on depressive symptoms right after the training (g = 0.81, p < 0.01) and at follow-up (g = 1.19, p < 0.01), as well as medium effects on anxiety (g = 0.44, p = 0.01) and emotion regulation (g = 0.48, p < 0.01). Between-group meta-analysis showed a medium effect on depressive symptoms (g = 0.49, p < 0.01) and a large effect on anxiety (g = 0.77, p = 0.01). However, the between-studies heterogeneity is very high. The use of RT-fMRI-NF as a treatment for psychiatric symptoms is promising, however, further double-blind, multicentric, randomized-controlled trials are warranted.

Dysfunctional temporal stages of eye-gaze perception in adults with ADHD: A high-density EEG study.

ADHD has been associated with social cognitive impairments across the lifespan, but no studies have specifically addressed the presence of abnormalities in eye-gaze processing in the adult brain. This study investigated the neural basis of eye-gaze perception in adults with ADHD using event-related potentials (ERP). Twenty-three ADHD and 23 controls performed a delayed face-matching task with neutral faces that had either direct or averted gaze. ERPs were classified using microstate analyses. ADHD and controls displayed similar P100 and N170 microstates. ADHD was associated with cluster abnormalities in the attention-sensitive P200 to direct gaze, and in the N250 related to facial recognition. For direct gaze, source localization revealed reduced activity in ADHD for the P200 in the left/midline cerebellum, as well as in a cingulate-occipital network at the N250. These results suggest brain impairments involving eye-gaze decoding in adults with ADHD, suggestive of neural signatures associated with this disorder in adulthood.

Identifying Disease-Specific Neural Reactivity to Psychosocial Stress in Borderline Personality Disorder.

BACKGROUND: Patients with borderline personality disorder (BPD) typically present emotion dysregulation (ED) when faced with adversity. However, it is argued that altered stress response may be more influenced by ED than BPD-specific traits. Here, we investigated this issue with functional magnetic resonance imaging using another ED condition as clinical control, i.e., bipolar disorder (BD), and controlling for ED traits. METHODS: We recruited 17 patients with BD, 24 patients with BPD, and 32 healthy control (HC) subjects. We adapted a functional magnetic resonance imaging-compatible psychosocial stressor task (Montreal Imaging Stress Task) in which participants are placed under time pressure when performing mental calculations and then receive immediate performance feedback (positive, negative, and neutral). ED traits were measured via self-report questionnaires targeting cognitive emotion dysregulation, affective lability, and trait anger and anxiety. RESULTS: Relative to patients with BD and HC subjects, patients with BPD exhibited overactive corticolimbic reactivity across all conditions, particularly in self-monitoring and emotion regulation regions such as the orbitofrontal cortex and anterior insula, even when controlling for ED. Conversely, patients with BD exhibited hypoactive corticolimbic reactivity to all feedback conditions compared with patients with BPD and HC subjects, even after controlling for ED. HC subjects exhibited significantly lower amygdala/hippocampus activity compared with both clinical groups, although this did not survive when controlling for ED. CONCLUSIONS: This study provides new insight into BPD-specific neural stress responding, suggesting hyperactive self- and emotion-regulatory neural psychosocial stress responding, independent of ED traits. The findings also highlight the importance of considering BPD as a diagnostic profile distinguishable from other ED disorder clinical groups.

Randomized controlled trial of a mindfulness-based intervention in adolescents from the general population: The Mindfulteen neuroimaging study protocol.

AIM: Adolescence is a period of vulnerability to stress. Increased anxiety during this period has been associated with the later development of mental disorders, hence the growing interest for interventions that could decrease stress reactivity and improve cognitive control in adolescents. Mindfulness-based interventions have demonstrated their efficacy on stress reactivity and anxiety in adults, but evidence is lacking in youth. METHODS: The Mindfulteen Study is a 3-year longitudinal cohort with a nested randomized controlled trial examining the effectiveness of mindfulness-based interventions for adolescents. Young adolescents from the general population, aged between 13 and 15 years old, with no history of current mental health disorder (apart from past mood disorders or current anxiety disorders) are included and stratified into low or high anxiety based on trait anxiety scores before being randomized to early or late 8-week intervention groups. Primary outcomes are based on neuroimaging data (i.e., structural and functional measures in the cortico-limbic network) while secondary outcomes are psychological (i.e., anxiety and stress-associated dimensions) and biological (i.e., cortisol, inflammatory and redox markers). Assessments are performed at baseline, immediately after intervention or waiting time and after 18 months of intervention. CONCLUSION: To the best of our knowledge, this is the first randomized controlled trail examining the effect of a mindfulness-based intervention in young adolescents from the general population based on the measurement and analyses of psychological, neuroimaging and biological data.

Irritability Is Associated With Decreased Cortical Surface Area and Anxiety With Decreased Gyrification During Brain Development.

Background: Brain development is of utmost importance for the emergence of psychiatric disorders, as the most severe of them arise before 25 years old. However, little is known regarding how early transdiagnostic symptoms, in a dimensional framework, are associated with cortical development. Anxiety and irritability are central vulnerability traits for subsequent mood and anxiety disorders. In this study, we investigate how these dimensions are related to structural changes in the brain to understand how they may increase the transition risk to full-blown disorders. Methods: We used the opportunity of an open access developmental cohort, the Healthy Brain Network, to investigate associations between cortical surface markers and irritability and anxiety scores as measured by parents and self-reports. Results: We found that in 658 young people (with a mean age of 11.6) the parental report of irritability is associated with decreased surface area in the bilateral rostral prefrontal cortex and the precuneus. Furthermore, parental reports of anxiety were associated with decreased local gyrification index in the anterior cingulate cortex and dorsomedial prefrontal cortex. Conclusions: These results are consistent with current models of emotion regulation network maturation, showing decreased surface area or gyrification index in regions associated with impaired affective control in mood and anxiety disorders. Our results highlight how dimensional traits may increase vulnerability for these disorders.

Mood disorders disrupt the functional dynamics, not spatial organization of brain resting state networks.

Spontaneous fluctuations in the blood oxygenation level dependent signal measured through resting-state functional magnetic resonance imaging have been corroborated to aggregate into multiple functional networks. Abnormal resting brain activity is observed in mood disorder patients, however with inconsistent results. How do such alterations relate to clinical symptoms; e.g., level of depression and rumination tendencies? Here we recovered spatially and temporally overlapping functional networks from 31 mood disorder patients and healthy controls during rest, by applying novel methods that identify transient changes in spontaneous brain activity. Our unique approach disentangles the dynamic engagement of resting-state networks unconstrained by the slow hemodynamic response. This time-varying characterization provides moment-to-moment information about functional networks in terms of their durations and dynamic coupling, and offers novel evidence for selective contributionsto particular clinical symptoms. Patients showed increased duration of default-mode network (DMN), increased duration and occurrence of posterior DMN as well as insula- and amygdala-centered networks, but decreased occurrence of visual and anterior salience networks. Coupling between limbic (insula and amygdala) networks was also reduced. Depression level modulated DMN duration, whereas intrusive thoughts correlated with occurrence of insula and posterior DMN. Anatomical network organization was similar to controls. In sum, altered brain dynamics in mood disorder patients appear to mediate distinct clinical dimensions including increased self-processing, and decreased attention to external world.