Scopolamine is a muscarinic receptor antagonist and is widely utilized as a “memory-loss model.” However, its impact across different memory and attention tasks and using different modes of administration has yet to be clearly evaluated. This systematic review and meta-analysis investigates the effect of scopolamine, across all routes of administration and across different dosages, on memory and attention performance in healthy humans (PROSPERO ID: CRD42024531634).

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched (on 20 April 2024) for studies that utilized scopolamine and assessed memory and/or attention. Random-effects meta-analyses were conducted across a range of memory and attention tasks using “Comprehensive Meta-Analysis,” Version 3, to evaluate differential pharmacological effects on cognitive tasks between the scopolamine and placebo groups.

Forty-six studies fulfilled the inclusion and exclusion criteria. Scopolamine negatively impaired performance on all memory tasks (immediate memory, delayed recall, digit span, Buschke selective reminding task, and recognition memory) and led to slower reaction times for three of the five attention tasks examined (choice reaction time, simple reaction time, and rapid visual information processing) compared to placebo. Scopolamine’s negative effect on memory and attention was greater with injectable (e.g., intramuscular, intravenous, and subcutaneous) compared to non-injectable routes of administration (e.g., intranasal, oral, and transdermal).

This study supports the use of scopolamine as a “memory-loss model,” particularly when given by an injectable route of administration. Future clinical trials should evaluate the bioavailability of scopolamine across different routes of administration to ensure therapeutic benefits outweigh any potential adverse cognitive effects.

Individuals with a psychiatric inpatient admission in adolescence have a high risk of schizophrenia-spectrum disorders (SSDs) when followed to adulthood. Whether psychotic symptoms predict subsequent SSDs in inpatient cohorts, however, is an important unanswered question.

The sample consisted of adolescents (aged 13–17) admitted to psychiatric inpatient care (Oulu, Finland) from April 2001 to March 2006. Psychotic symptoms were assessed with the Schedule for Affective Disorders and Schizophrenia. Specialized health care use and diagnoses were followed up in national health care registers until June 2023. Cox regression was used to predict SSDs by the presence of baseline psychotic symptoms.

Of 404 adolescent inpatients admitted with non-psychotic mental disorders, 28% (n = 113) reported psychotic symptoms: 17% (n = 68) subthreshold and 11% (n = 45) full threshold. By the end of follow-up, 23% of the total cohort went on to be diagnosed with an SSD. Subthreshold psychotic symptoms did not differentiate patients who would subsequently develop SSDs (cumulative incidence 24%; HR = 1.42, 95%CI = 0.81–2.50). Full-threshold psychotic symptoms, on the other hand, were associated with an increased risk of subsequent SSDs (cumulative incidence 33%; HR = 2.00, 95%CI = 1.12–3.56). Most subsequent SSDs (83%), however, occurred in individuals who had not reported threshold psychotic symptoms during inpatient admission.

There was a high risk of subsequent SSDs among adolescent psychiatry inpatients when followed over time. SSDs were not predicted by subthreshold psychotic symptoms. Full-threshold psychotic symptoms were associated with an increased risk of subsequent SSDs, though with low sensitivity.

Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FAT) and higher extracellular free water (FW).

Thirty-seven SZ and 129 healthy controls (HC) were grouped into the ‘none/low’ or ‘high’ CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FAT and FW.

SZ displayed lower FAT within the corpus callosum and corona radiata compared to HC (p < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FAT (p < 0.05, TFCE) and higher FW (p < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group (p > 0.05, TFCE).

These novel findings suggest that the impact of CT on lower FAT may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.

Cannabis is the most commonly used illicit substance in Ireland and globally. It is most likely to be used in adolescence, a period of biopsychosocial vulnerability to maladaptive behaviours. This study aims to investigate the risk and protective factors for cannabis use among adolescents.

This study is a secondary analysis of the cross-sectional Planet Youth survey (2021). The sample comprised 4,404 adolescents aged 15–16 from one urban and two rural areas in Ireland. The outcome of interest was current cannabis use, defined as cannabis use within the last 30 days. Independent variables i.e., risk and protective factors, were selected a priori following a literature review. Associations between cannabis use and the independent variables were explored using mixed-effects logistic regressions.

The prevalence of current cannabis use was 7.3% and did not differ significantly between males and females. In fully-adjusted models, significant risk factors for cannabis use were: Having peers that used cannabis (Adjusted Odds Ration (aOR) 10.17, 95% CI: 5.96–17.35); Parental ambivalence towards cannabis use (aOR 3.69, 95% CI: 2.41–5.66); Perception of cannabis as non-harmful (aOR 2.32,95% CI 1.56–£.45): Other substance use (aORs ranging from 2-67–3.15); Peer pressure to use cannabis (aOR 1.85,95% CI 1.05–3.26), and Low parental supervision (aOR 1.11, 95% CI: 1.01–1.22).

This study identified key individual, peer-to-peer and parental risk factors associated with adolescent cannabis use, several of which have the potential to be modified through drug prevention strategies.

The clinical high-risk state for psychosis (CHR) is associated with alterations in grey matter volume (GMV) in various regions such as the hippocampus (Vissink et al. BP:GOS 2022; 2(2) 147-152). Within the scope of the North American Prodrome Longitudinal Study (NAPLS-2; Cannon et al. AM J Psychiatry 2016; 173(10), 980-988), a publicly available risk calculator based on clinical variables was developed to assess the likelihood of individuals to transition to psychosis within a 2-year period.

In the current study, we aim to examine the association between GMV and NAPLS-2 risk scores calculated for individuals with CHR and recent-onset depression (ROD), taking a transdiagnostic approach on the transition to psychosis.

The sample consisted of 315 CHR (M = 23.85, SD = ± 5.64; female: 164) and 295 ROD (M = 25.11, SD = ± 6.21; female: 144) patients from the multi-site Personalised Prognostic Tools for Early Psychosis Management (PRONIA) Study (Koutsouleris et al. JAMA Psychiatry 2018; 57(11), 1156-1172). Risk scores were calculated using the six clinical and neurocognitive variables included in the NAPLS-2 risk calculator that were significant for predicting psychosis. Further, we derived smoothed GMV maps from T1-weighted structural magnetic resonance imaging using a full width at half maximum kernel size of 8 mm. We employed a multiple regression design in SPM12 to examine associations between risk scores and GMV. On the whole-brain level, we calculated permutation-based threshold-free cluster enhancement (TFCE) contrasts using the TFCE toolbox. Additionally, we calculated t-contrasts within a region-of-interest (ROI) analysis encompassing the hippocampus. All results were thresholded at p < 0.05 with family wise error correction to address multiple comparisons.

Our analysis revealed that linear GMV increases in the right middle and superior frontal gyrus (kE= 2726 voxels) were significantly associated with higher risk for psychosis transition within two years (see figure 1, highlighted in blue). In the ROI analysis, we found a significant negative linear association between GMV decreases in the left hippocampus (kE = 353 voxels) and higher risk for psychosis transition (see figure 1, highlighted in red).

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GMV reductions in the hippocampus have frequently been observed in CHR and psychosis patients (Vissink et al. BP:GOS 2022; 2(2) 147-152), therefore our results further highlight the crucial role of this region in the progression of the disease. There is limited evidence on GMV increases in CHR patients. However, the GMV increase we found in the frontal pole may reflect compensatory mechanisms of the brain in the development of psychosis. In addition, we were able to provide biological validation of the NAPLS-2 risk calculator and its assessment of risk for transition to psychosis.

None Declared

Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Psychotic experiences (PE) occur most often in childhood, at the same age many mental disorders (MD) develop. There is growing evidence that those who report PE and MD show poorer health outcomes. If this occurs in psychosocial outcomes e.g. self-esteem, stress, mental distress, or social support, is under examined. Attachment anxiety and avoidance are the dimensions of attachment, which is hypothesized to develop in infancy as a mechanism for interpersonal relationships in times of need.

To examine the role of transient childhood PE in adult psychosocial outcomes, in those with and without MD. Additionally, to examine if the dimensions of attachment attenuate this model.

One hundred and three participants attended baseline (age 11 – 13) and 10-year follow-up. PE and MD were collected using the Schedule for Affective Disorders and Schizophrenia for School-aged Children, Present & Lifetime Version. Attachment and outcomes were collected using self-report measures. Analysis compared those with PE, MD and PE and MD, to healthy controls.

PE in childhood was associated with lower self-esteem and lower perceived social support from friends. Lower self-esteem in adulthood was more pronounced in those reporting PE and MD, and was additionally associated with stress in relationships, daily life, and mental distress. Childhood MD without PE was not significantly associated with any psychosocial outcomes. Attachment dimensions significantly attenuated the relationship between PE and self-esteem.

This paper illustrates the significant association of childhood PE on adult outcomes, independent of the effect of co-occurring MD, and demonstrate attachment dimensions role in this model.

No significant relationships.

The association between low birth weight and attention problems in childhood has been replicated many times (e.g. Momany, Kamradt, & Nikolas, 2018). However birth weight is unlikely the aetiological start-point of this association, as birth weight is itself the product of many prenatal factors e.g. gestational complications, maternal toxin exposure during pregnancy and basic demographics.

We explore (1) which prenatal factors best predict attention problems in two independant population-based cohorts of children (2) which associations, if any, are moderated by sex and (3) we report accuracy statistics of our prenatal prediction algorithm for attention problems.

Participants were children aged 9 from ABCD study from the United States (N > 9,000) and the Growing Up in Ireland (GUI) study from Ireland (N > 6,000). Selected variables included familial pscyhiatric history, maternal smoking during gestation, prescription and non-prescription drug-use during gestation and a variety of gestational complications. All interactions with sex were also included. We used 5-fold cross-validation and elastic net regression (glmnet) to identify the optimal predictors of attention problems (measured by CBCL and SDQ).

Strongest predictors of attention problems in the U.S. cohort included male sex, number of drugs used during pregnancy, number of family members with a history of mental illness, and number of gestational complications. Sex interacted with several of these risks. Protective factors included being a twin/triplet, being Asian, having higher household income and higher parental education level.

Several risk factors for childhood attention problems were identified across both cohorts, supporting their generalizabilty. Other findings were cohort-specific.

No significant relationships.

Area-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with decreased gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral anterior cingulate cortex (rACC).

We hypothesize that greater ARI will be associated with reduced right posterior CMFG and rACC GMVs.

Data were collected at baseline as part of the North American Prodrome Longitudinal Study. Counties where participants resided during childhood were geographically coded using the US Censuses to area-level factors. ARI was defined as the percentage of residents living in a different house five years ago. Generalized linear mixed models tested associations between ARI and GMVs.

This study included 29 HC and 64 CHR-P individuals who were aged 12 to 24 years, had remained in their baseline residential area, and had magnetic resonance imaging scans. ARI was associated with reduced right CMFG (adjusted β = -0.258; 95% CI = -0.502 – -0.015) and right rACC volumes (adjusted β = -0.318; 95% CI = -0.612 – -0.023). The interaction terms (ARI X diagnostic group) in the prediction of both brain regions were not significant, indicating that the relationships between ARI and regional brain volumes held for both CHR-P and HCs.

Like urban upbringing, ARI may be an important social environmental characteristic that adversely impacts brain regions related to schizophrenia.

No significant relationships.

To reduce both inappropriate testing for and diagnosis of healthcare-onset (HO) Clostridioides difficile infections (CDIs).

We performed a retrospective analysis of C. difficile testing from hospitalized children before (October 2017–October 2018) and after (November 2018–October 2020) implementing restrictive computerized provider order entry (CPOE).

Study sites included hospital A (a ∼250-bed freestanding children’s hospital) and hospital B (a ∼100-bed children’s hospital within a larger hospital) that are part of the same multicampus institution.

In October 2018, we implemented CPOE. No testing was allowed for infants aged ≤12 months, approval of the infectious disease team was required to test children aged 13–23 months, and pathology residents’ approval was required to test all patients aged ≥24 months with recent laxative, stool softener, or enema use. Interrupted time series analysis and Mann-Whitney U test were used for analysis.

An interrupted time series analysis revealed that from October 2017 to October 2020, the numbers of tests ordered and samples sent significantly decreased in all age groups (P < .05). The monthly median number of HO-CDI cases significantly decreased after implementation of the restrictive CPOE in children aged 13–23 months (P < .001) and all ages combined (P = .003).

Restrictive CPOE for CDI in pediatrics was successfully implemented and sustained. Diagnostic stewardship for CDI is likely cost-saving and could decrease misdiagnosis, unnecessary antibiotic therapy, and overestimation of HO-CDI rates.

Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen.

We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history.

Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations.

Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14–19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33–52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71–4.75; 2014, aOR = 4.52, 2.78–7.35).

Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations.

Psychotic experiences (PEs) are relatively common in childhood and adolescence and are associated with increased risk of functional issues and psychiatric illness in young adulthood, and PEs that recur are associated with increased risk of poorer psychiatric and functional outcomes. Childhood adversity is a well-established risk factor for PEs. The aim of this study was to investigate (1) the relationship between childhood adversity and recurring PEs in adolescence and (2) candidate mediators of that relationship.

We used data from Cohort ‘98 of the Growing Up in Ireland study (n = 6039) at three time points (ages 9, 13 and 17) to investigate the relationship between childhood adversity (parent-reported at age 9), recurring PEs (measured using a subset of the Adolescent Psychotic-like Symptoms Screener at ages 13 and 17). The mediating roles of parent–child relationship, internalising and externalising difficulties, self-concept, physical activity, dietary quality, perceived neighbourhood safety and friendship quantity were investigated using the KHB path decomposition method.

Childhood adversity was associated with an increased risk of recurring PEs with a population attributable fraction of 23%. Internalising difficulties and self-concept explained 13% of the relationship between childhood adversity and PEs suggesting a partial mediation. A significant direct effect remained between childhood adversity and recurring PEs.

The established relationship between childhood adversity and PEs may be mainly driven by the relationship between childhood adversity and recurring PEs. Internalising difficulties and self-concept together mediate part of the relationship between childhood adversity and recurring PEs.