The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.

Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.

Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Treatment guidelines recommend evidence-based psychological therapies for adults with intellectual disabilities with co-occurring anxiety or depression. No previous research has explored the effectiveness of these therapies in mainstream psychological therapy settings or outside specialist settings.

To evaluate the effectiveness of psychological therapies delivered in routine primary care settings for people with intellectual disability who are experiencing co-occurring depression or anxiety.

This study used linked electronic healthcare records of 2 048 542 adults who received a course of NHS Talking Therapies for anxiety and depression in England between 2012 and 2019 to build a retrospective, observational cohort of individuals with intellectual disability, matched 1:2 with individuals without intellectual disability. Logistic regressions were used to compare metrics of symptom improvement and deterioration used in the national programme, on the basis of depression and anxiety measures collected before and at the last attended therapy session.

The study included 6870 adults with intellectual disability and 2 041 672 adults without intellectual disability. In unadjusted analyses, symptoms improved on average for people with intellectual disability after a course of therapy, but these individuals experienced poorer outcomes compared with those without intellectual disability (reliable improvement 60.2% for people with intellectual disability v. 69.2% for people without intellectual disability, odds ratio 0.66, 95% CI 0.63–0.70; reliable deterioration 10.3% for people with intellectual disability v. 5.7% for those without intellectual disability, odds ratio 1.89, 95% CI 1.75–2.04). After propensity score matching, some differences were attenuated (reliable improvement, adjusted odds ratio 0.97, 95% CI 1.91–1.04), but some outcomes remained poorer for people with intellectual disability (reliable deterioration, adjusted odds ratio 1.28, 95% CI 1.16–1.42).

Evidence-based psychological therapies may be effective for adults with intellectual disability, but their outcomes may be similar to (for improvement and recovery) or poorer than (for deterioration) those for adults without intellectual disability. Future work should investigate the impact of adaptations of therapies for those with intellectual disability to make such interventions more effective and accessible for this population.

According to the aberrant salience proposal, reward processing abnormality, specifically erroneous reward prediction error (RPE) signaling due to stimulus-independent release of dopamine, underlies delusions in schizophrenia. However, no studies to date have examined RPE-associated brain activations in relation to this symptom.

Seventy-eight patients with a DSM-5 diagnosis of schizophrenia/schizoaffective disorder and 43 healthy individuals underwent fMRI while they performed a probabilistic monetary reward task designed to generate a measure of RPE. Ratings of delusions and referentiality were made in the patients.

Using whole-brain, voxel-based analysis, schizophrenia patients showed only minor differences in RPE-associated activation compared to healthy controls. Within the patient group, however, severity of delusions was inversely associated with RPE-associated activation in areas including the caudate nucleus, the thalamus and the left pallidum, as well as the lateral frontal cortex bilaterally, the pre- and postcentral gyrus and supplementary motor area, the middle cingulate gyrus, and parts of the temporal and parietal cortex. A broadly similar pattern of association was seen for referentiality.

According to this study, while patients with schizophrenia as a group do not show marked alterations in RPE signaling, delusions and referentiality are associated with reduced activation in parts of the prefrontal cortex and the basal ganglia, though not specifically the ventral striatum. The direction of the changes is on the face of it contrary to that predicted by aberrant salience theory.

Pediatric patients with frontal lobe epilepsy (FLE) have higher rates of attention deficit hyperactivity disorder (ADHD), as well as executive functioning (EF) and fine motor (FM) challenges. Relations between these constructs have been established in youth with ADHD and are supported by FM and EF skill involvement in frontal-subcortical systems. Still, they are not well understood in pediatric FLE. We hypothesized that poorer FM performance would be related to greater executive dysfunction and ADHD symptomatology in this group.

47 children and adolescents with FLE (AgeM=12.47, SD=5.18; IQM=84.07; SD=17.56; Age of Seizure OnsetM=6.85, SD=4.64; right-handed: n=34; left-handed: n=10; Unclear: n=3) were enrolled in the Pediatric Epilepsy Research Consortium dataset as part of their phase I epilepsy surgical evaluation. Participants were selected if they had unifocal FLE and completed the Lafayette Grooved Pegboard (GP). Seizure lateralization (left-sided: n=19; right-sided: n=26; bilateral: n=2) and localization were established via data (e.g., EEG, MRI) presented at a multidisciplinary team case conference. Patients completed neuropsychological measures of FM, attention, and EF. Parents also completed questionnaires inquiring about their child’s everyday EF and ADHD symptomatology. Correlational analyses were conducted to examine FM, EF, and ADHD relations.

Dominant hand (DH) manual dexterity (GP) was related to parent-reported EF (Behavior Rating Inventory of Executive Function, Second Edition [BRIEF-2]-Global Executive Composite [GEC]: r(15) =-.70, p<.01, d=1.96). While not statistically significant, medium to large effect sizes were found for GP DH and parent-reported inattention (Behavior Assessment System for Children, Third Edition [BASC-3]-Attention Problems: r(12)=-.39, p=.17, d=.85) and hyperactivity/impulsivity (BASC-3-Hyperactivity: r(11)= -.44, p=.13, d=.98), as well as performance-based attention (Conners Continuous Performance Test, Third Edition -Omission Errors: r(12)=-.35, p=.22, d=.41), working memory (Wechsler Intelligence Scale for Children - Fifth Edition [WISC-V]-Digit Span [DS]: r(19)=.38, p=.09, d=.82) and cognitive flexibility (Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Category Switching: r(13)=.46, p=.08, d=1.04); this suggests that these relations may exist but that our study was underpowered to detect them. Non-dominant hand (NDH) manual dexterity was related to performance-based working memory (WISC-V-DS: r(19)=.50, p<.01, d=1.12) and cognitive flexibility (D-KEFS-Trails Making Test Number-Letter Switching: r(17)=.64, p<.01, d=1.67). Again, while underpowered, medium to large effect sizes were found for GP NDH and parent-reported EF (BRIEF-2 GEC: r(15) =-.45, p=.07, d=1.01) and performance-based phonemic fluency (D-KEFS-Letter Fluency: r(13)=.31, p=.20, d=.65).

Our findings suggest that FM, EF, and ADHD are related in youth with FLE; however, these relations appear to vary by skill and hand. We posit that our findings are due in part to the frontal-cerebellar networks given their anatomic proximity between frontal motor areas and the dorsolateral prefrontal cortex - as well as their shared functional involvement in these networks. Future studies should evaluate the predictive validity of initial FM skills for later executive dysfunction and ADHD symptomatology in FLE. If such relations emerge, contributions of early FM interventions on EF development should be examined. Further replication of these findings with a larger sample is warranted.

Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances.

We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis–Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups.

FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio.

Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England.

108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models.

Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71–0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74–0.87, p < 0.0001). Referral to substance use services and ‘other’ services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78–0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79–0.94, p = 0.001).

SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

It has been suggested that dysregulation of sex hormones is associated with schizophrenia. However, obesity and metabolic syndrome are very common between schizophrenic patients, and it can also dysregulate sex hormones so they could act as confounders.

To determine if estradiol and progesterone are abnormally elevated regardless of obesity or metabolic syndrome in men with SCZ.

We measured serum levels of progesterone and estradiol in 56 schizophrenic male patients at treatment with a depot antipsychotic. Subsequently, we studied the association or independence of our results with obesity or metabolic syndrome by a Chi Square Test.

66.07% of our patients elevated progesterone levels, 19.64% of our patients elevated estradiol levels, and 16.07% of our patients elevated both, progesterone and estradiol, simultaneously. We found no relationship between increased estradiol and / or progesterone with obesity and / or metabolic syndrome.

Estradiol and progesterone are abnormally elevated regardless of obesity and / or metabolic syndrome in male schizophrenic patients on depot treatment.

No significant relationships.

Health technology reassessment (HTR) is a structured evidence-based assessment of an existing technology in comparison to its alternatives. The process results in the following four outputs: (i) increased use; (ii) decreased use; (iii) no change; or (iv) de-adoption. However, implementing these outputs remains a challenge. Knowledge translation (KT) can be applied to implement findings from the HTR process. This study sought to identify which characteristics of KT theories, models, and frameworks (TMFs) could be useful, specifically for decreasing the use of or de-adopting a technology.

A qualitative descriptive approach was used to ascertain the perspectives of international KT and HTR experts on the characteristics of KT TMFs for decreasing the use of or de-adopting a technology. One-to-one semi-structured interviews were conducted. Interviews were audio recorded and transcribed verbatim. Themes and sub-themes were deduced from the data through framework analysis using the following five distinctive steps: familiarization; identifying an analytic framework; indexing; charting; and mapping and interpretation. Themes and sub-themes were also mapped to existing KT TMFs.

Thirteen experts participated. The following three themes emerged as ideal characteristics of a KT TMF: (i) principles foundational for HTR: evidence-based, high usability, patient-centered, and ability to apply to micro, meso, and macro levels; (ii) levers of change: characterized as positive, neutral, or negative influences for changing behavior; and (iii) steps for knowledge to action: build the case for HTR, adapt research knowledge, assess context, select, tailor, and implement interventions, and assess impact. The Consolidated Framework for Implementation Research had the greatest number of ideal characteristics.

Application of KT TMFs to the HTR process has not been clearly established. This is the first study to provide an understanding of characteristics within KT TMFs that could be considered by users undertaking projects to decrease or de-adopt technologies. Characteristics to be considered within a KT TMF for implementing HTR outputs were identified. Consideration of these characteristics may guide users in choosing which KT TMF(s) to use when undertaking HTR projects.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.