The prediction of alcohol consumption in youths and particularly biomarkers of resilience, is critical for early intervention to reduce the risk of subsequent harmful alcohol use.

At baseline, the longitudinal relaxation rate (R1), indexing grey matter myelination (i.e. myeloarchitecture), was assessed in 86 adolescents/young adults (mean age = 21.76, range: 15.75–26.67 years). The Alcohol Use Disorder Identification Test (AUDIT) was assessed at baseline, 1- and 2-year follow-ups (12- and 24-months post-baseline). We used a whole brain data-driven approach controlled for age, gender, impulsivity and other substance and behavioural addiction measures, such as problematic cannabis use, drug use-related problems, internet gaming, pornography use, binge eating, and levels of externalization, to predict the change in AUDIT scores from R1.

Greater baseline bilateral anterior insular and subcallosal cingulate R1 (cluster-corrected family-wise error p < 0.05) predict a lower risk for harmful alcohol use (measured as a reduction in AUDIT scores) at 2-year follow-up. Control analyses show that other grey matter measures (local volume or fractional anisotropy) did not reveal such an association. An atlas-based machine learning approach further confirms the findings.

The insula is critically involved in predictive coding of autonomic function relevant to subjective alcohol cue/craving states and risky decision-making processes. The subcallosal cingulate is an essential node underlying emotion regulation and involved in negative emotionality addiction theories. Our findings highlight insular and cingulate myeloarchitecture as a potential protective biomarker that predicts resilience to alcohol misuse in youths, providing novel identifiers for early intervention.

The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Childhood adversity is associated with abnormalities in brain structure, but this association has not been tested for childhood unpredictability, one form of adversity. We studied whether abnormalities in gray matter volume (GMV) could be a mechanism linking childhood unpredictability and psychopathology, over and above the effect of childhood trauma.

Participants were 158 right-handed healthy young adults (aged 17–28 years, M = 22.07, s.d. = 2.08; 66.46% female) who underwent structural magnetic resonance imaging measurements and provided retrospective reports of childhood unpredictability. The anxiety and depression subscales of the self-report Brief Symptom Inventory-53 were used to index psychopathology.

Whole-brain voxel-based morphometric analyses showed that after controlling for the effect of childhood trauma, childhood unpredictability was correlated with greater GMV in bilateral frontal pole, bilateral precuneus, bilateral postcentral gyrus, right hemisphere of fusiform, and lingual gyrus, and left hemisphere of ventrolateral prefrontal cortex as well as occipital gyrus. Greater GMV in bilateral frontal pole, bilateral precuneus, and bilateral postcentral gyrus mediated associations between unpredictability and symptoms of depression and anxiety.

The findings suggest that childhood unpredictability could exact unique effects on neural development, over and above the effect of childhood trauma. These findings are relevant for understanding the occurrence of psychopathology following childhood unpredictability and have implications for intervention.

Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the ‘Imperial Psychedelic Predictor Scale’ (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience.

Using four independent datasets in which the IPPS was completed prospectively – two online surveys of ‘naturalistic’ use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) – we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS.

Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of ‘mystical’, ‘challenging’, and ‘emotional breakthrough’ experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance.

Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.

Multiple risk behaviours (MRBs), typically beginning in adolescence, are associated with increased risk of adverse health and social outcomes. The association between autism and MRBs is little understood.

Data were from the Avon Longitudinal Study of Parents and Children, an UK-based longitudinal, birth cohort study. Exposures were diagnosed autism and four autistic traits: social communication difficulties, pragmatic language, repetitive behaviours and reduced sociability. Outcomes were participation in up to 14 risk behaviours, including alcohol consumption, smoking, risky sexual behaviours and physical inactivity. Outcome data were collected at ages approximately 12, 14, 16 and 18.

Up to 4300 participants were included in latent basis growth curve analyses with adjustment for confounders. Social communication difficulties were associated with an above average level of MRBs engagement at ~12 years (mean difference β 0.26; 95% CI 0.13–0.40), and above average rate of engagement from ages ~12–18 (β 0.08; 95% CI 0.02–0.13). Repetitive behaviours were associated with above average levels of engagement in MRBs at ~12 years (β 0.24; 95% CI 0.09–0.38). Contrastingly, reduced sociability was associated with a reduced rate of engagement in MRBs from ages ~12–18 (β −0.06; 95% CI −0.11 to −0.02). In sex-specific analyses, persisting differences in MRB engagement patterns from ages ~12–18 were observed in males with social communication difficulties and females with reduced sociability temperament.

Having elevated levels of some autistic traits appear to have differentiated effects on MRB engagement patterns. These findings could reflect difficulties fitting in and/or coping mechanisms relating to difficulties with fitting in.

The psychosis continuum implies that subclinical psychotic experiences (PEs) can be differentiated from clinically relevant expressions since they are not accompanied by a ‘need for care’.

Using data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 34 653), the current study examined variation in functioning, symptomology and aetiological risk across the psychosis phenotype [i.e. variation from (i) no PEs, ‘No PEs’ to (ii) non-distressing PEs, ‘PE-Experienced Only’ to (iii) distressing PEs, ‘PE-Impaired’ to (iv) clinically defined psychotic disorder, ‘Diagnosed’].

A graded trend was present such that, compared to those with no PEs, the Diagnosed group had the poorest functioning, followed by the PE-Impaired then PE-Experienced Only groups. In relation to symptom expression, the PE-Impaired group were more likely than the PE-Experienced Only and the Diagnosed groups to endorse most PEs. Predictors of group membership tended to vary quantitatively rather than qualitatively. Trauma, current mental health diagnoses (anxiety and depression) and drug use variables differentiated between all levels of the continuum, with the exception of the extreme end (PE-Impaired v. Diagnosed). Only a few variables distinguished groups at the upper end of the continuum: female sex, older age, unemployment, parental mental health hospitalisation and lower likelihood of having experienced physical assault.

The findings highlight the importance of continuum-based interpretations of the psychosis phenotype and afford valuable opportunities to consider if and how impairment, symptom expression and risk change along the continuum.

The stressful minority position of transgender persons may result in a high risk of psychosis. Conflicting data suggest that the observed risk depends on setting of recruitment. We assessed the relative risk of non-affective psychotic disorder (NAPD) in a large, representative cohort of transgender persons.

This cohort was composed using: data on legal sex change from the Dutch population registry and data on dispensing of cross-sex hormones (route 1), and a registry of insurance claims from mental health care including persons with a diagnosis of gender identity disorder (DSM-IV) or gender dysphoria (DSM-5) (route 2). They were matched by sex at birth, calendar year and country of birth to controls from the general population. Transgender persons (N = 5564) and controls (N = 27 820), aged 16–60 years at 1 January 2011, were followed until the first insurance claim for NAPD in 2011–2019.

The incidence rate ratio (IRR) of NAPD for transgender persons selected exclusively through route 1 (N = 3859, IRR = 2.00, 95%-CI 1.52–2.63) was increased, but significantly lower than the IRRs for those selected exclusively through route 2 (N = 694, IRR = 22.15, 95%-CI 13.91–35.28) and for those found by both routes (N = 1011, IRR = 5.17, 95%-CI 3.57–7.49; p value for differences in IRR < 0.001).

This study supports the social defeat-hypothesis of NAPD. The results also show the presence of a substantial number of transgender persons with severe psychiatric problems who have not (yet) taken steps to gender-affirmative care.

An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks.

Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30–58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects.

Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline.

Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.

Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis.

A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate.

We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = −0.80; 95% CI −1.49 to −0.11), followed by Lactobacillus (SMD = −0.49; 95% CI −0.85 to −0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = −0.41; 95% CI −0.73 to −0.10) had a positive effect on depression.

The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.

Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents.

Data were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends.

Participants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted β = 0.05; 95% CI: 0.01–0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted β = −0.02; 95% CI: −0.04 to <−0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted β = 0.07; 95% CI: 0.03–0.11). However, among those with more close friends, the association was non-significant (adjusted β = 0.03; 95% CI: −0.01 to 0.07).

Greater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.

Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects.

In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used.

In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41–0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001).

This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

Post-traumatic stress symptoms (PTSS) were the most frequently reported mental health concern for youth during COVID-19, yet variations in youth's PTSS responses warrant empirical consideration. Features of the caregiving environment influence youth's responses to environmental stressors, and youth's parasympathetic nervous system regulation may qualify the magnitude and/or direction of these effects. This prospective investigation evaluated diathesis stress and differential susceptibility models of caregiving and parasympathetic influences on youth's PTSS responses to COVID-19.

Participants were 225 caregiver-youth dyads (youth 49.8% female at birth; 88.4% non-white) followed from childhood through adolescence and COVID-19. Youth's resting respiratory sinus arrhythmia (RSA; Mage = 6.11, s.d. = 0.21), caregiving features (i.e. attachment security [youth Mage = 12.24, s.d. = 0.35] and caregiver internalizing psychopathology [caregiver Mage = 39.29, s.d. = 6.78]) were assessed pre-pandemic. Youth's PTSS was assessed one year prior to the US COVID-19 pandemic (Mage = 14.24, s.d. = 0.50) and during the spring of 2020 at the height of the pandemic (Mage = 15.23, s.d. = 0.57).

Youth's PTSS increased during COVID-19. Youth with relatively high resting RSA evidenced the lowest PTSS when their caregiving environment featured high attachment security or low caregiver internalizing problems, but the highest PTSS when their caregiving environment featured low attachment security or high caregiver internalizing problems. In contrast, PTSS levels of youth with relatively low or average resting RSA did not differ significantly depending on attachment security or caregiver internalizing.

Results are consistent with a differential susceptibility hypothesis, wherein relatively high resting RSA conferred heightened sensitivity to caregiving environments in a for-better-and-for-worse manner during COVID-19.