BackgroundNon suicidal self injury (NSSI) is a public health concern, and its prevalence has increased significantly following the COVID-19 pandemic. Despite its rising incidence, the neurobiological mechanisms underlying NSSI behaviour in adolescents remain poorly understood.MethodsA sample of 89 adolescents (46 NSSI positive, 43 NSSI negative) aged 15.39 ± 1.77 years was recruited from clinical settings. NSSI behaviour and psychological resilience were evaluated. Resting-state functional magnetic resonance imaging (Rs-fMRI) was conducted to examine brain connectivity patterns. Data analysis incorporated descriptive and inferential statistics, as well as support vector machine algorithms, to identify the neural correlates of NSSI and resilience.ResultsThe NSSI positive group had significantly lower resilience scores (M = 23.41, SD = 7.95). Connectivity between the sensorimotor and limbic networks was negatively associated with NSSI (r = −0.222, p < 0.05), while connectivity between the sensorimotor and subcortical networks showed a positive association (r = 0.201, p < 0.05). Stronger connectivity between dorsal attention and default mode networks indirectly reduced NSSI by enhancing psychological resilience, highlighting resilience as a critical protective factor.ConclusionThese findings underscore the importance of targeting specific brain connectivity patterns and enhancing psychological resilience as crucial components of neurobiologically informed interventions.

The International Society for Bipolar Disorders (ISBD) Chronobiology and Chronotherapy Task Force conducted a comprehensive review to deliver concise evidence-based recommendations on the use of bright light therapy (BLT) for bipolar disorder (BD). Adjunctive BLT is likely an efficacious acute treatment for bipolar depression as implicated by higher quality evidence. The position of maintenance BLT for relapse prevention awaits further investigation. Protocols of effective BLT in BD are similar to parameters indicated for treatment of seasonal and non-seasonal major depressive disorder. Anti-manic prophylaxis (especially for BD-I) and clinical monitoring are recommended with initiation of and ongoing light treatment. Administer BLT daily, preferably in the morning or at mid-day. If mornings are prohibitive, then mid-day exposure, implemented to avoid excessively early wake times, is an acceptable alternative. Informed by the literature, target 30 min/day of BLT exposure. Patients wary of emergent hypomania or partial responders, can initiate 15 min/day and increase by 15 min each week to full response (or 30-60 min/day by the fourth week). Consider patient centred outcome assessments to evaluate mood response, safety and side effects. Clinical improvement is typically observed within 1-2 weeks, with response/remission expected by 4-6 weeks. Integration of BLT with other chronotherapeutic strategies may enhance long-term efficacy.

BackgroundBright light therapy (BLT) demonstrates efficacy in alleviating subthreshold depression (StD) among young adults. The amygdala plays a critical role in depression.MethodsStD subjects were divided into BLT group (N=47) and placebo group (N=42). Depression severity was assessed using HAM-D, Centre for Epidemiologic Studies Depression Scale (CES-D) and Beck Depression Inventory (BDI) pre-/post-8-week intervention. Structural/resting-state fMRI scan was conducted. Seed-based static FC (sFC) and dynamic FC (dFC) analyses of the bilateral amygdala and their subfields were conducted.ResultsCompared to placebo, BLT showed reduced depression scale, and increased sFC of right basolateral amygdala (BLA)/superficial amygdala (SFA)-right middle temporal gyrus (MTG) and dFC of right centralmedial amygdala (CMA) and right inferior orbital frontal gyrus, and decreased sFC of right amygdalostriatal transition/CMA- left thalamus and dFC of right SFA- right medial prefrontal cortex after intervention; while the whole amygdala and its subnuclei volume did not change significantly after BLT. Right BLA-MTG sFC changes positively correlated with BDI improvement. Baseline amygdala sFC/dFC predicted post-BLT symptom changes. BLT-induced right BLA sFC alterations spatially correlated with 5-HT1A/5-HT2A receptor distributions, and right CMA dFC changes with 5-HT1A.ConclusionsFindings suggest BLT modulates amygdala-thalamocortical circuits and serotonergic pathways, highlighting FC biomarkers for treatment efficacy assessment.Trial Registration ClinicalTrials.gov IdentifierChiCTR2000032633.

The global population is ageing rapidly, with the number of individuals aged 60 and older reaching 1 billion in 2019 and expected to double by 2050. As people age, neuropsychological health often deteriorates, leading to a higher prevalence of age-related depression. Symptoms may include anxiety, apathy, mood instability, sadness, and, in severe cases, suicidal thoughts. Depression in the elderly is a widespread concern, and conventional treatments such as antidepressants are often limited by side effects, reduced efficacy, and complications arising from polypharmacy. In response, novel therapeutic approaches are being explored, including psychedelic interventions. Recent clinical and preclinical studies suggest that psychedelics could offer a promising treatment for major depressive disorder (MDD) in older adults. These compounds, known for their profound neurobiological effects, have gained attention for their potential to address depression where traditional therapies fall short. This review aims to examine the therapeutic promise of psychedelic substances, focusing on those that show potential for treating MDD in the elderly. We also explore the underlying mechanisms through which psychedelics may exert their effects and highlight the preclinical models that support their use. Finally, we address safety considerations and propose strategies to enhance the effectiveness and safety of psychedelics in future clinical trials, offering new hope for treating age-related depressive disorders.

This study investigated the emotional symptom profiles and treatment responses in patients exhibiting overlapping physical symptoms to compare differences between Somatic Symptom Disorder (SSD) and Panic Disorder (PD). Pharmacotherapy outcomes were analysed in 208 outpatients with SSD (n = 94) and PD (n = 114). Stepwise multivariable logistic regression identified predictors of treatment response, considering variables such as the Clinical Global Impression-Severity (CGI-S), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory, and State-Trait Anger Expression Inventory. Network analysis explored emotional patterns by estimating network structures for each group. The overall response rate to pharmacotherapy was 23.6% (49/208), with no significant difference between groups. Baseline CGI-S and BDI-II scores were significant predictors of treatment response in both groups, while social phobia score was a significant predictor in PD. Depression and anxiety were related to physical symptoms in both groups, but anger was significantly associated only in SSD. Network analysis revealed that depression was central to other symptoms in SSD, while anxiety was the core symptom in PD, indicating different emotional drivers between the disorders. This study suggests the differences in emotional symptom profiles between SSD and PD. Findings suggest different mechanisms, considering the role of anger in SSD, highlighting the need for more personalised treatments for each disorder.

Psychedelics are gaining recognition for their therapeutic potential in mental health treatment, yet societal attitudes remain divided, influenced by both skepticism and curiosity. This study aimed to develop and validate a scale assessing attitudes toward psychedelics. Study 1 (n = 1000, convenience sample) explored the factor structure, identifying two dimensions: Openness toward Psychedelics and Concerns toward Psychedelics. Study 2 (n = 843, representative Polish sample) confirmed the scale's validity. The Concerns factor negatively correlated with meaning in life, while the Openness factor was positively associated with openness to experience, agreeableness, conscientiousness, mindfulness, meaning in life, and nature-relatedness. These associations suggest that individuals with greater openness and psychological flexibility may hold more favorable views on psychedelics. The Concerns and Openness towards Psychedelics Scale (COPS) is a psychometrically sound tool for assessing attitudes toward psychedelics. Its meaningful correlations with established psychological constructs underscore its utility in research and public health. By providing insight into societal perceptions, COPS may help inform discussions on psychedelic therapy, policy, and education, ultimately fostering a more nuanced understanding of their potential benefits and risks.

Emerging observational studies have indicated the association between autism spectrum disorder (ASD) and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), whereas the causality remains unknown. Summary-level data from large-scale genome-wide association (GWAS) studies of IBD and ASD were retrieved. Mendelian randomisation analyses were performed with a series of sensitivity tests. Genetic predisposition to ASD was not associated with the risk of IBD (odds ratio [OR] = 0.99, 95% confidence interval [CI = 0.91-1.06, p = 0.70; OR [95% CI]: 1.03 [0.93-1.13], p = 0.58 for CD; OR [95% CI]: 0.96 [0.87-1.05], p = 0.37 for UC) in the IIBDGC dataset. In the FinnGen dataset, their causal effects were unfounded (OR [95% CI]: 1.04 [0.94-1.15], p = 0.49 for IBD; OR [95% CI]: 1.08 [0.89-1.31], p = 0.42 for CD; OR [95% CI]: 1.00 [0.88-1.13], p = 0.95 for UC). In the meta-analysis of two datasets, the OR was 1.01 (95% CI 0.96-1.07, p = 0.45). For the risk of ASD under genetic liability to IBD, the OR from meta-analysis was 1.03 (95% CI 1.01-1.05, p = 0.01). Our findings indicate genetic predisposition to ASD might not increase the risk of IBD, whereas genetic liability to IBD is associated with an increased risk of ASD. Further investigations using more powerful datasets are warranted.

IntroductionAssessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder.MethodsFifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF, and FAAH SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR.ResultsSLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = .007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity (p = .003) and positively associated with inhibitory control performance (p = .006), respectively. BDNF Val66Met was associated with the severity of use (p = .008). SLC18A2 and FAAH mRNA levels were lower in people who use methamphetamine relative to controls (p = .021 and .010, respectively).ConclusionsSLC18A1 is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.

Negative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one's life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms. This study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories. Dose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation. Controllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.

The increasing prevalence and burden of suicide have led to numerous studies to identify its risk factors. Cannabis is the most common illicit substance detected in suicide victims' toxicology tests. This study aims to identify and appraise systematic reviews investigating suicidality after using cannabis and cannabinoids. Seven databases and two registries were searched without restrictions for systematic reviews investigating cannabis effects on suicidality. AMSTAR-2 was used for quality assessment and corrected covered area and citation matrix were used to determine overlap. Twenty-five studies were included, of which 24 were on recreational use and one was on therapeutic use. Only three of the studies on recreational use reported no effect or inconsistent results. Evidence generally showed a positive association between cannabis use and suicidal ideation and attempt among the general population, military veterans, and bipolar or major depression patients. A bidirectional causal association between cannabis and suicidal ideation was also mentioned. Moreover, a younger age of initiation, long-term use, and heavy consumption were reported to be associated with even worse suicidal outcomes. On the contrary, current evidence indicates that the therapeutic cannabis is safe. In conclusion, the literature supports the cannabis-suicidality association in recreational use but considers cannabidiol safe for treatment. Further studies with quantitative and interventional approaches are recommended.