Neurocognitive consequences of adolescent sleep disruptions and their relationship to psychosis vulnerability: a longitudinal cohort study.

Adolescence is a key period for neurocognitive maturation where deviation from normal developmental trajectories may be tied to adverse mental health outcomes. Cognitive disruptions have been noted in populations at risk for psychosis and are known to accompany periods of sleep deprivation. This study aims to assess the role of cognition as a mediator between sleep disruptions and psychosis risk. A cohort of 3801 high school students (51% female, mean age = 12.8, SD = 0.45 years) was recruited from 31 Montreal high schools. Measures of sleep, psychotic-like experiences, inhibition, working memory, perceptual reasoning, and delayed recall were collected from participants on a yearly basis over the five years of their high school education. A multi-level model mediation analysis was performed controlling for sex and time squared. Response inhibition was shown to be associated with, and to mediate (B = -0.005, SD = 0.003, p = 0.005*) the relationship between sleep disruptions (B = -0.011, SD = 0.004, p < 0.001*) and psychotic-like experiences (B = 0.411, SD = 0.170, p = 0.005*). Spatial working memory deficits on a given year were associated with a higher frequency of psychotic-like experiences that same year (B = -0.046, SD = 0.018, p = 0.005*) and the following year (B = -0.051, SD = 0.023, p = 0.010*), but were not associated with sleep disturbances. No significant associations were found between our variables of interest and either delayed recall or perceptual reasoning at the within person level. Findings from this large longitudinal study provide evidence that the association between sleep disruptions and psychosis risk is specifically mediated by inhibitory rather than general cognitive impairments. The association of spatial working memory, response inhibition, and sleep disruptions with psychotic-like experiences suggests that these factors may represent potential targets for preventative interventions.

Effects of Recreational Cannabis Legalization on Mental Health: Scoping Review.

OBJECTIVE: Recreational cannabis legalization (RCL) is expanding rapidly. RCL's effects on mental health issues are of particular concern because cannabis use is more frequent among people receiving psychiatric care and is associated with several psychiatric disorders. The authors conducted a scoping review to examine the evidence and discern gaps in the literature concerning the effects of RCL on mental health and to assess the factors responsible for an observed heterogeneity in research results. METHODS: This scoping literature review followed PRISMA guidelines. Five databases-MEDLINE, CINAHL, Embase, APA PsycInfo, and Web of Science-were searched for English- or French-language reports published between January 1, 2012, and April 30, 2023. RESULTS: Twenty-eight studies from the United States and Canada were found. The studies were classified by category of the study's data (patients receiving psychiatric care [k=1], death records [k=4], emergency department or hospital records [k=10], and the general population [k=13]) and by the diagnosis (schizophrenia or psychoses, mood disorders, anxiety disorders and symptoms, suicide or suicidal ideation, or other mental health issues) examined. The review findings revealed a paucity of research and indicated mixed and largely inconclusive results of the studies examined. Research gaps were found in the examination of potential changes in cannabis use patterns among people receiving psychiatric care and in the availability of longitudinal studies. CONCLUSIONS: Clinicians, researchers, and policy makers need to collaborate to address the research gaps and to develop evidence-based policies that reflect a thorough understanding of the effects associated with RCL.

Dysconnectivity of the Nucleus Accumbens and Amygdala in Youths with Thought Problems: A Dimensional Approach.

Background: Youths with thought problems (TP) are at risk to develop psychosis and obsessive-compulsive disorder (OCD). Yet, the pathophysiological mechanisms underpinning TP are still unclear. Functional magnetic resonance imaging (fMRI) studies have shown that striatal and limbic alterations are associated with psychosis-like and obsessive-like symptoms in individuals at clinical risk for psychosis, schizophrenia, and OCD. More specifically, nucleus accumbens (NAcc) and amygdala are mainly involved in these associations. The current study aims to investigate the neural correlates of TP in youth populations using a dimensional approach and explore potential cognitive functions and neurotransmitters associated with it. Methods: Seed-to-voxels functional connectivity analyses using NAcc and amygdala as regions-of-interest were conducted with resting-state fMRI data obtained from 1360 young individuals, and potential confounders related to TP such as anxiety and cognitive functions were included as covariates in multiple regression analyses. Replicability was tested in using an adult cohort. In addition, functional decoding and neurochemical correlation analyses were performed to identify the associated cognitive functions and neurotransmitters. Results: The altered functional connectivities between the right NAcc and posterior parahippocampal gyrus, between the right amygdala and lateral prefrontal cortex, and between the left amygdala and the secondary visual area were the best predictors of TP in multiple regression model. These functional connections are mainly involved in social cognition and reward processing. Conclusions: The results show that alterations in the functional connectivity of the NAcc and the amygdala in neural pathways involved in social cognition and reward processing are associated with severity of TP in youths.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

The Signature Biobank: A longitudinal biopsychosocial repository of psychiatric emergency patients.

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit.

Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders.

BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. METHODS: To uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ. Rather than relying on a classical voxel level coordinate-based approach, our procedure extracted relevant neuroanatomical labels from text data and examined findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients/7414 controls), BD (81 studies, 3330 patients/4096 patients) and/or SZ (223 studies, 11,168 patients/11,754 controls). Permutation testing revealed commonalities and differences in hypoconnectivity and hyperconnectivity patterns across disorders. RESULTS: Hypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the three disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD. CONCLUSIONS: Findings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate between mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience.

Is There a Dose-Response Relationship Between Cannabis Use and Violence? A Longitudinal Study in Individuals with Severe Mental Disorders.

Introduction: Recent longitudinal studies point toward the existence of a positive relationship between cannabis use and violence in people with severe mental disorders (SMD). However, the existence of a dose-response relationship between the frequency/severity of cannabis use and violence has seldom been investigated. Therefore, this study aims to determine if such a relationship exists in a psychiatric population. Methods: To do so, a total of 98 outpatients (81 males and 17 females, all over 18 years of age) with SMD were recruited at the Institut universitaire de santé mentale de Montréal (Montréal, Canada) and included in the analyses. Clinical evaluations were conducted every 3 months for a year. Substance use, violent behaviors, and potential covariables were assessed through self-reported assessments, urinary testing, as well as clinical, criminal, and police records. Using generalized estimating equations, the association between cannabis use frequency (nonusers, occasional, regular, and frequent users) and violence was investigated, as well as the association between the severity of cannabis use and violent behaviors. Results: It was found that cannabis use frequency and severity were significant predictors of violent behaviors. After adjustment for time, age, sex, ethnicity, diagnoses, impulsivity, and use of alcohol and stimulants, odds ratios were of 1.91 (p<0.001) between each frequency profile and 1.040 (p<0.001) for each increase of one point of the severity of cannabis use score (ranging from 0 to 79). Conclusions: Despite the high attrition rate, these findings may have important implications for clinicians as cannabis use may have serious consequences in psychiatric populations. Nevertheless, the mechanisms underlying this association remain unclear.

Losing the chain of thought: A meta-analysis of functional neuroimaging studies using verbal tasks in schizophrenia.

BACKGROUND: Disorganization symptoms are a main feature of schizophrenia, which include illogical and incoherent thinking, circumstantiality, tangentiality and loose associations. As these symptoms entail language deficits, several functional neuroimaging studies have been performed in schizophrenia using verbal tasks, producing somewhat heterogenous results. Hence, we performed a meta-analysis seeking to identify the most reliable neural alterations observed in schizophrenia patients during such tasks. METHODS: Web of Sciences, PubMed, and EMBASE were searched for functional neuroimaging studies during verbal tasks (e.g. verbal fluency and semantic processing) in schizophrenia. Out of 795 screened articles, 33 were eligible for this meta-analysis. A coordinated-based meta-analysis was performed with the activation likelihood estimation (ALE) approach, using the cluster-level family-wise error (FWE) correction set at p < 0.05. RESULTS: In schizophrenia, hyperactivations were observed in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) and hypoactivations were observed in the right IFG, the precentral gyrus and the left caudate nucleus. Another analysis pooling hyper- and hypoactivations revealed altered activations, firstly, in the left IFG and MFG, secondly, in the left precentral gyrus, IFG and insula, and, thirdly, in the left angular gyrus and precuneus. In the light of these results, not only classic language-related regions are abnormally activated during verbal tasks in schizophrenia, but also brain regions involved in executive functions, autobiographical memory and, unexpectedly, in motor functions. Further functional neuroimaging studies are needed to investigate the role of the striatum in linguistic sequencing in schizophrenia.

Functional Connectivity of the Nucleus Accumbens across Variants of Callous-Unemotional Traits: A Resting-State fMRI Study in Children and Adolescents.

A large body of literature suggests that the primary (high callousness-unemotional traits [CU] and low anxiety) and secondary (high CU traits and anxiety) variants of psychopathy significantly differ in terms of their clinical profiles. However, little is known about their neurobiological differences. While few studies showed that variants differ in brain activity during fear processing, it remains unknown whether they also show atypical functioning in motivational and reward system. Latent Profile Analysis (LPA) was conducted on a large sample of adolescents (n = 1416) to identify variants based on their levels of callousness and anxiety. Seed-to-voxel connectivity analysis was subsequently performed on resting-state fMRI data to compare connectivity patterns of the nucleus accumbens across subgroups. LPA failed to identify the primary variant when using total score of CU traits. Using a family-wise cluster correction, groups did not differ on functional connectivity. However, at an uncorrected threshold the secondary variant showed distinct functional connectivity between the nucleus accumbens and posterior insula, lateral orbitofrontal cortex, supplementary motor area, and parietal regions. Secondary LPA analysis using only the callousness subscale successfully distinguish both variants. Group differences replicated results of deficits in functional connectivity between the nucleus accumbens and posterior insula and supplementary motor area, but additionally showed effect in the superior temporal gyrus which was specific to the primary variant. The current study supports the importance of examining the neurobiological markers across subgroups of adolescents at risk for conduct problems to precise our understanding of this heterogeneous population.

The company you keep: The neglected role of affiliating with delinquent friends in the development of the cannabis-violence link.

A growing body of research suggests a potential role of cannabis use on aggressive behaviors. In literature on adolescents, the lack of consideration of important confounders, such as adolescent's affiliation with delinquent peers, limits the possibility to determine whether there might be a direct or indirect link between cannabis use and aggression. Therefore, we sought to examine the effect of delinquent peers on the association between cannabis use and violence. We re-analyzed data from 850 ninth graders who were followed from mid-adolescence to early adulthood. Generalized Estimations Equations (GEE) were conducted to examine whether affiliation with delinquent peers may mediate the relationship between cannabis use and violence. Cross-Lagged Panel Models were also conducted to estimate the directionality of these relationships over time. We additionally tested whether similar relationships may be identifiable when examining rule-breaking behaviors and/or alcohol use. GEE models revealed that both cannabis use and affiliation with delinquent peers were statistically associated with aggressive behaviors. Cannabis use, alcohol use and delinquent peers also predicted rule-breaking behaviors. More precisely, cross-lagged models showed that affiliation with delinquent peers played a partially mediating role in the cannabis-aggression link, and that similar cross-lagged estimates were observed when examining rule-breaking behaviors instead of aggression. Our results indicate that cannabis use may be associated with aggression as well as rule-breaking behaviors, suggesting a broader effect on conduct problems. More importantly, our study highlights the non-negligible role of affiliating with delinquent peers during adolescence.

Auditory Steady-State Responses in Schizophrenia: An Updated Meta-Analysis.

This meta-analysis investigates auditory steady-state responses (ASSRs) as potential biomarkers of schizophrenia, focusing on previously unexplored clinical populations, frequencies, and variables. We examined 37 studies, encompassing a diverse cohort of 1788 patients with schizophrenia, including 208 patients with first-episode psychosis, 281 at-risk individuals, and 1603 healthy controls. The results indicate moderate reductions in 40 Hz ASSRs in schizophrenia patients, with significantly greater reductions in first-episode psychosis patients and minimal changes in at-risk individuals. These results call into question the expected progression of ASSR alterations across all stages of schizophrenia. The analysis also revealed the sensitivity of ASSR alterations at 40 Hz to various factors, including stimulus type, level of analysis, and attentional focus. In conclusion, our research highlights ASSRs, particularly at 40 Hz, as potential biomarkers of schizophrenia, revealing varied implications across different stages of the disorder. This study enriches our understanding of ASSRs in schizophrenia, highlighting their potential diagnostic and therapeutic relevance, particularly in the early stages of the disease.

Enhancing Predictive Power: Integrating a Linear Support Vector Classifier with Logistic Regression for Patient Outcome Prognosis in Virtual Reality Therapy for Treatment-Resistant Schizophrenia.

(1) Background: Approximately 30% of schizophrenia patients are known to be treatment-resistant. For these cases, more personalized approaches must be developed. Virtual reality therapeutic approaches such as avatar therapy (AT) are currently undergoing investigations to address these patients' needs. To further tailor the therapeutic trajectory of patients presenting with this complex presentation of schizophrenia, quantitative insight about the therapeutic process is warranted. The aim of the study is to combine a classification model with a regression model with the aim of predicting the therapeutic outcomes of patients based on the interactions taking place during their first immersive session of virtual reality therapy. (2) Methods: A combination of a Linear Support Vector Classifier and logistic regression was conducted over a dataset comprising 162 verbatims of the immersive sessions of 18 patients who previously underwent AT. As a testing dataset, 17 participants, unknown to the dataset, had their first immersive session presented to the combinatory model to predict their clinical outcome. (3) Results: The model accurately predicted the clinical outcome for 15 out of the 17 participants. Classification of the therapeutic interactions achieved an accuracy of 63%. (4) Conclusion: To our knowledge, this is the first attempt to predict the outcome of psychotherapy patients based on the content of their interactions with their therapist. These results are important as they open the door to personalization of psychotherapy based on quantitative information about the interactions taking place during AT.

Regional cerebral blood flow at rest in schizophrenia and major depressive disorder: A functional neuroimaging meta-analysis.

Severe mental disorders (SMDs) such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BD) are associated with altered brain function. Neuroimaging studies have illustrated spontaneous activity alterations across SMDs, but no meta-analysis has directly compared resting-state regional cerebral blood flow (rCBF) with one another. We conducted a meta-analysis of PET, SPECT and ASL neuroimaging studies to identify specific alterations of rCBF at rest in SMDs. Included are 20 studies in MDD, and 18 studies in SCZ. Due to the insufficient number of studies in BD, this disorder was left out of the analyses. Compared to controls, the SCZ group displayed reduced rCBF in the triangular part of the left inferior frontal gyrus and in the medial orbital part of the bilateral superior frontal gyrus. After correction, only a small cluster in the right inferior frontal gyrus exhibited reduced rCBF in MDD, compared to controls. Differences were found in these brain regions between SCZ and MDD. SCZ displayed reduced rCBF at rest in regions associated with default-mode, reward processing and language processing. MDD was associated with reduced rCBF in a cluster involved in response inhibition. Our meta-analysis highlights differences in the resting-state rCBF alterations between SCZ and MDD.

Serotonin Transporter mRNA Expression Is Reduced in the Peripheral Blood Mononuclear Cells of Subjects with Major Depression but Normal in Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) and major depression disorder (MDD) frequently co-occur. Both disorders may share common serotonergic alterations, although there is less evidence of such alterations in FM. It is also unclear as to whether these alterations are persistent over time or transient. The objectives of this study were to (i) examine the changes in mRNA expression of serotonin transporter (SERT) on the surface of peripheral blood mononuclear cells (PBMCs) in FM, MDD, and the FM + MDD subjects compared to healthy controls, and to (ii) evaluate the effect of drug treatment on SERT expression. METHODS: PBMCs were isolated from FM, MDD, FM + MDD, and control subjects. SERT expression was analyzed at the mRNA level via quantitative real-time polymerase chain reaction. Statistical analyses were performed using analyses of variance and linear mixed-effects models. RESULTS: SERT mRNA expression was significantly reduced in MDD subjects compared to controls (p < 0.001), but not in FM nor in FM + MDD subjects. Although the drug treatments improved symptoms in FM, MDD, and FM + MDD subjects, they had no significant effect on SERT mRNA expression. CONCLUSIONS: These results corroborate the role of the SERT in the pathophysiology of MDD, but not in FM, and show that the decreased mRNA expression of SERT is a persistent, rather than transient, phenomenon.

Alpha and theta oscillations during the cognitive reappraisal of aversive pictures: A spatio-temporal qEEG investigation.

CONTEXT: Emotion regulation is a set of processes responsible for controlling, evaluating and adjusting reactions to achieve a goal. Results derived from magnetic resonance imaging agreed on the involvement of frontal and limbic structures in this process. Findings using cognition and physiology interactions are still scarce but suggest a role of alpha rhythm in emotional induction and for theta in regulation. OBJECTIVES AND HYPOTHESES: Our goal was to investigate alpha and theta rhythm during the reappraisal of aversive stimuli. We hypothesized that an implication of alpha rhythm in emotional induction only and an increase in prefrontal theta rhythm positively correlated with successful regulation. METHOD: Twenty-four healthy participants were recorded with 64 EEG electrodes while asked to watch or reappraise negative pictures passively. Theta and alpha rhythms were compared across maintain, decrease and increase regulation conditions, and a source localization estimated the generators. RESULTS: Theta activity was consistently higher in the upregulation than in the maintenance condition (p = .04) for the entire control period, but mainly at the beginning of regulation (1-3 s) for low-theta and later (5-7 s) for high-theta. Moreover, our results confirm that a low-theta generator correlated with mainly the middle frontal gyrus and the anterior dorsal cingulate cortex during upregulation. Theta was sensitive to emotion upregulation, whereas the alpha oscillation was non-sensitive to emotion induction and regulation. CONCLUSION: Theta rhythm was involved explicitly in emotion upregulation processes that occur at a definite time during reappraisal, whereas the alpha rhythm was not altered by emotion induction and regulation.

Exploration of the role of emotional expression of treatment-resistant schizophrenia patients having followed virtual reality therapy: a content analysis.

BACKGROUND: Emotional responses are an important component of psychotherapeutic processes. Avatar therapy (AT) is a virtual reality-based therapy currently being developed and studied for patients suffering from treatment resistant schizophrenia. Considering the importance of identifying emotions in therapeutical processes and their impact on the therapeutic outcome, an exploration of such emotions is needed. METHODS: The aim of this study is to identify the underlying emotions at the core of the patient-Avatar interaction during AT by content analysis of immersive sessions transcripts and audio recordings. A content analysis of AT transcripts and audio recordings using iterative categorization was conducted for 16 patients suffering from TRS who underwent AT between 2017 and 2022 (128 transcripts and 128 audio recordings). An iterative categorization technique was conducted to identify the different emotions expressed by the patient and the Avatar during the immersive sessions. RESULTS: The following emotions were identified in this study: Anger, Contempt/ Disgust, Fear, Sadness, Shame/ Embarrassment, Interest, Surprise, Joy and Neutral. Patients expressed mostly neutral, joy and anger emotions whereas the Avatar expressed predominantly interest, disgust/contempt, and neutral emotions. CONCLUSIONS: This study portrays a first qualitative insight on the emotions that are expressed in AT and serves as a steppingstone for further investigation in the role of emotions in the therapeutic outcomes of AT.

Meta-review on the efficacy of psychological therapies for the treatment of substance use disorders.

This meta-review aimed to summarize the current state of knowledge provided by meta-analyzes on the efficacy of psychotherapies for substance use disorders. A systematic search was performed in PubMed, PsycINFO, Web of Science and Google Scholar. Meta-analyzes were included if they quantitatively examined the efficacy of a psychotherapy on substance use. Among the 6866 potential articles that were screened for eligibility, 23 meta-analyzes were eligible (78 effect sizes). Each meta-analysis included 2-156 studies, with samples ranging between approximately 130 to over 33,000 individuals. The quality of evidence was evaluated as being globally of low to moderate quality. Substances were categorized as: alcohol (k = 12), cannabis (k = 7), stimulants (k = 4), opioids (k = 3) and benzodiazepines (k = 1). Interventions comprised brief intervention, cognitive-behavioral therapy, contingency management, voucher-based reinforcement therapy, motivational interview, motivational enhancement therapy, significant other people involved in the treatment, and cue-expose therapy. Concerning solely significant results, small benefits were observed for significant other people involved in treatment, motivational interviewing, and the combination of cognitive-behavioral therapy with motivational interviewing for alcohol use disorder. Likewise, small-to-moderate effects were found for motivational approaches, and cognitive-behavioral therapy as well as the combination of cognitive-behavioral therapy and motivational enhancement therapy in the case of cannabis use disorder. Small effects were observed for contingency management as well as cognitive behavioral-therapy for amphetamine-type use disorder. Small effects were similarly found for contingency management for cocaine use disorder. Concerning opioid use disorder, moderate effects were observed for contingency management and voucher-based reinforcement intervention. For benzodiazepine use disorder, small effects were noted for cognitive-behavioral therapy with taper. Results often displayed small to moderate heterogeneity when reported and were generally compared to inactive controls, such as treatment-as-usual. In all, the psychosocial treatments for substance use disorders included in this meta-review have shown to be at best moderately effective over inactive controls in the short term. Nevertheless, further trials are needed as well as meta-analyzes on interventions not included in this meta-review.

Altered functional connectivity of the amygdala across variants of callous-unemotional traits: A resting-state fMRI study in children and adolescents.

Over the past years, research has shown that primary (high callousness and low anxiety) and secondary (high callousness and anxiety) variants of CU traits may be associated with opposite amygdala activity (hypo- and hyper-reactivity, respectively). However, their differences in amygdala functional connectivity remains largely unexplored. We conducted a Latent Profile Analysis on a large sample of adolescents (n = 1416) to identify homogeneous subgroups with different levels of callousness and anxiety. We then performed a seed-to-voxel connectivity analysis on resting-state fMRI data to compare subgroups on connectivity patterns of the amygdala. We examined the results in relation to conduct problems to identify potential neural risk factors. The Latent Profile Analysis revealed four subgroups, including the primary and secondary variants, anxious, and typically developing adolescents. The seed-to-voxel analyses showed that the primary variant was mainly characterized by increased connectivity between the left amygdala and left thalamus. The secondary variant exhibited deficient connectivity between the amygdala and the dorsomedial prefrontal cortex, temporo-parietal junction, premotor, and postcentral gyrus. Both variants showed increased connectivity between the left amygdala and the right thalamus but exhibited opposite functional connectivity between the left amygdala and the parahippocampal gyrus. Dimensional analyses indicated that conduct problems may play a mediating role between callousness and amygdala-dmPFC functional connectivity across youths with already high levels of callousness. Our study highlights that both variants differ in the functional connectivity of the amygdala. Our results support the importance of disentangling the heterogeneity of adolescents at risk for conduct problems in neuroimaging.

Avatar Intervention for Cannabis Use Disorder in Individuals with Severe Mental Disorders: A Pilot Study.

Cannabis use disorder (CUD) is a complex issue, even more so when it is comorbid with a severe mental disorder (SMD). Available interventions are at best slightly effective, and their effects are not maintained over time. Therefore, the integration of virtual reality (VR) may increase efficacy; however, it has not yet been investigated in the treatment of CUD. A novel approach, avatar intervention for CUD, uses existing therapeutic techniques from other recommended therapies (e.g., cognitive behavioral methods, motivational interviewing) and allows participants to practice them in real-time. During immersive sessions, participants are invited to interact with an avatar representing a significant person related to their drug use. This pilot clinical trial aimed to evaluate the short-term efficacity of avatar intervention for CUD on 19 participants with a dual diagnosis of SMD and CUD. Results showed a significant moderate reduction in the quantity of cannabis use (Cohen's d = 0.611, p = 0.004), which was confirmed via urinary quantification of cannabis use. Overall, this unique intervention shows promising results. Longer-term results, as well as comparison with classical interventions in a larger sample, are warranted through a future single-blind randomized controlled trial.