This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase 1 and 2 (IDO1, IDO2), kynurenine aminotransferase 1 and 2 (KAT1, KAT2), kynurenine monooxygenase (KMO) and kynureninase (KYNU) in medicated patients with depression (n = 74) compared to age- and sex-matched healthy controls (n = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.

HAM-D24 was used to evaluate depression severity. Whole blood mRNA expression was assessed using quantitative real-time polymerase chain reaction.

KAT1, KYNU and IDO2 were significantly reduced in patient samples compared to control samples, though results did not survive statistical adjustment for covariates or multiple comparisons. ECT did not alter KP enzyme mRNA expression. Changes in IDO1 and KMO and change in HAM-D24 score post-ECT were negatively correlated in subgroups of patients with unipolar depression (IDO1 only), psychotic depression and ECT responders and remitters. Further exploratory correlative analyses revealed altered association patterns between KP enzyme expression, KP metabolites, NR3C1 and IL-6 in depressed patients pre- and post-ECT.

Further studies are warranted to determine if KP measures have sufficient sensitivity, specificity and predictive value to be integrated into stress and immune associated biomarker panels to aid patient stratification at diagnosis and in predicting treatment response to antidepressant therapy.

Many autistic children experience difficulties in their communication and language skills development, with consequences for social development into adulthood, often resulting in challenges over the life-course and high economic impacts for individuals, families, and society. The Preschool Autism Communication Trial (PACT) intervention is effective in terms of improved social communication and some secondary outcomes. A previously published within-trial economic analysis found that results at 13 months did not support its cost-effectiveness. We modeled cost-effectiveness over 6 years and across four European countries.

Using simulation modeling, we built on economic analyses in the original trial, exploring longer-term cost-effectiveness at 6 years (in England). We adapted our model to undertake an economic analysis of PACT in Ireland, Italy, and Spain. Data on resource use were taken from the original trial and a more recent Irish observational study.

PACT is cost-saving over time from a societal perspective, even though we confirmed that, at 13 months post-delivery, PACT is more expensive than usual treatment (across all countries) when given to preschool autistic children. After 6 years, we found that PACT has lower costs than usual treatment in terms of unpaid care provided by parents (in all countries). Also, if we consider only out-of-pocket expenses from an Irish study, PACT costs less than usual treatment.

PACT may be recommended as a cost-saving early intervention for families with an autistic child.

Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life. Despite its personal, familial, and societal impact, Europe-wide harmonised guidelines are still lacking for early detection, diagnosis, and intervention, leading to an overall unsatisfactory autistic person and carer journey.

The care pathway for autistic children and adolescents was analysed in Italy, Spain and the UK from the perspective of carers (using a survey aimed at caregivers of autistic children 0–18 years old), the autistic community, and professionals in order to identify major barriers (treatment gaps) preventing carers from receiving information, support, and timely screening/diagnosis and intervention.

Across all three countries, analysis of the current care pathway showed: long waits from the time carers raised their first concerns about a child’s development and/or behaviour until screening and confirmed diagnosis; delayed or no access to intervention once a diagnosis was confirmed; limited information about autism and how to access early detection services; and deficient support for families throughout the journey.

These findings call for policy harmonisation in Europe to shorten long wait times for diagnosis and intervention and therefore, improve autistic people and their families’ journey experience and quality of life.

Autism and epilepsy often occur together. Epilepsy and other associated conditions have a substantial impact on the well-being of autistic people and their families, reduce quality of life, and increase premature mortality. Despite this, there is a lack of studies investigating the care pathway of autistic children with co-occurring epilepsy in Europe.

We analyzed the care pathway for autistic children with associated epilepsy in Italy, Spain, and the United Kingdom from the perspective of caregivers (using a survey aimed at caregivers of autistic children 0–18 years old), the autistic community, and professionals, in order to identify major barriers preventing caregivers and autistic children from receiving timely screening and treatment of possible co-occurring epilepsy.

Across all three countries, an analysis of the current care pathway showed a lack of systematic screening of epilepsy in all autistic children, lack of treatment of co-occurring epilepsy, and inappropriate use of antiepileptic drugs. A major challenge is the lack of evidence-based harmonized guidelines for autism with co-occurring epilepsy in these countries.

Our findings show both heterogeneity and major gaps in the care pathway for autism with associated epilepsy and the great efforts that caregivers must make for timely screening, diagnosis, and adequate management of epilepsy in autistic children. We call for policy harmonization in Europe in order to improve the experiences and quality of life of autistic people and their families.

Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Offspring exposed to prenatal maternal depression (PMD) are vulnerable to depression across their lifespan. The underlying cause(s) for this elevated intergenerational risk is most likely complex. However, depression is underpinned by a dysfunctional frontal-limbic network, associated with core information processing biases (e.g. attending more to sad stimuli). Aberrations in this network might mediate transmission of this vulnerability in infants exposed to PMD. In this study, we aimed to explore the association between foetal exposure to PMD and frontal-limbic network function in infancy, hypothesising that, in response to emotional sounds, infants exposed to PMD would exhibit atypical activity in these regions, relative to those not exposed to PMD.

We employed a novel functional magnetic resonance imaging sequence to compare brain function, whilst listening to emotional sounds, in 78 full-term infants (3–6 months of age) born to mothers with and without a diagnosis of PMD.

After exclusion of 19 datasets due to infants waking up, or moving excessively, we report between-group brain activity differences, between 29 infants exposed to PMD and 29 infants not exposed to PMD, occurring in temporal, striatal, amygdala/parahippocampal and frontal regions (p < 0.005). The offspring exposed to PMD exhibited a relative increase in activation to sad sounds and reduced (or unchanged) activation to happy sounds in frontal-limbic clusters.

Findings of a differential response to positive and negative valanced sounds by 3–6 months of age may have significant implications for our understanding of neural mechanisms that underpin the increased risk for later-life depression in this population.

Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions.

We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake.

We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome.

There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41–1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89–0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61–0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73–0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87–0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00–1.03).

We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.

Alexithymia (difficulties in identifying and describing emotion) is a transdiagnostic trait implicated in social–emotional and mental health problems in the general population. Many autistic individuals experience significant social-communication difficulties and elevated anxiety/depression and alexithymia. Nevertheless, the role of alexithymia in explaining individual variability in the quality/severity of social-communication difficulties and/or anxiety and depression symptoms in autism remains poorly understood.

In total, 337 adolescents and adults (autism N = 179) were assessed for alexithymia on the Toronto Alexithymia Scale and for social-communication difficulties, anxiety and depression symptoms. A total of 135 individuals (autism N = 76) were followed up 12–24 months later. We used regression models to establish cross-sectional and longitudinal associations between alexithymia, social-communication difficulties, anxiety and depression symptoms.

Autistic individuals reported significantly higher alexithymia than comparison individuals (p < 0.001, r effect size = 0.48), with 47.3% of autistic females and 21.0% of autistic males meeting cut-off for clinically relevant alexithymia (score ⩾61). Difficulties in describing feelings were particularly associated with current self-reported social-communication difficulties [p < 0.001, β = 0.57, 95% confidence interval (CI) 0.44–0.67] and predicted later social-communication difficulties (p = 0.02, β = 0.43, 95% CI 0.07–0.82). Difficulties in identifying feelings were particularly associated with current anxiety symptom severity (p < 0.001, β = 0.54, 95% CI 0.41–0.77) and predicted later anxiety (p = 0.01; β = 0.31, 95% CI 0.08–0.62).

Our findings suggest that difficulties in identifying v. describing emotion are associated with differential clinical outcomes in autism. Psychological therapies targeting emotional awareness may improve social-communication and anxiety symptoms in autism, potentially conferring long-term benefits.

ENT disease prevalence, risk factors and treatment vary between developed and developing countries. Health provision, particularly disease prevention strategies and surgery, in developing countries is poor, manifesting as a high frequency of common and preventable diseases. Healthcare systems in developing countries are unsustainable, and the technological advances that provide ENT surgery with novel diagnostic and treatment opportunities are inaccessible.

A multifaceted approach is essential to improve the care of patients with ENT diseases in developing countries. Public health efforts must focus on educating the local community, reducing high-risk behaviours and decreasing the frequency of preventable diseases. Governments must be pressured to prioritise the funding of long-term, sustainable efforts with effective disease prevention strategies. Providing local healthcare professionals with high-quality ENT training so that self-sustaining and low-cost care can be delivered, mainly in a primary care setting, is key.

Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.

To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).

Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).

Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.

Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.

Autism-spectrum disorder is increasingly recognised, with recent studies estimating that 1% of children in South London are affected. However, the biology of comorbid mental health problems in people with autism-spectrum disorder is poorly understood.

To investigate the brain anatomy of people with autism-spectrum disorder with and without psychosis.

We used in vivo magnetic resonance imaging and compared 30 adults with autism-spectrum disorder (14 with a history of psychosis) and 16 healthy controls.

Compared with controls both autism-spectrum disorder groups had significantly less grey matter bilaterally in the temporal lobes and the cerebellum. In contrast, they had increased grey matter in striatal regions. However, those with psychosis also had a significant reduction in grey matter content of frontal and occipital regions. Contrary to our expectation, within autism-spectrum disorder, comparisons revealed that psychosis was associated with a reduction in grey matter of the right insular cortex and bilaterally in the cerebellum extending into the fusiform gyrus and the lingual gyrus.

The presence of neurodevelopmental abnormalities normally associated with autism-spectrum disorder might represent an alternative ‘entry-point’ into a final common pathway of psychosis.

Lack of social interaction, which is characteristically seen in people with autistic-spectrum disorder, may be caused by malfunctioning of the frontostriatal reward systems. However, no reported in vivo brain imaging studies have investigated reward mechanisms in autistic-spectrum disorder.

To investigate functional brain activation during reward feedback in people with autistic-spectrum disorder and control individuals.

We used event-related functional magnetic resonance imaging to examine the neural substrates of monetary reward in individuals with autistic-spectrum disorder and matched controls.

When rewarded, individuals with autism compared with control individuals showed significantly greater brain activation in the left anterior cingulate gyrus. In addition, activation of this region was negatively correlated with social interaction as measured by the Autism Diagnostic Interview.

In people with autistic-spectrum disorder, achieving reward is associated with significant differences in the activation of areas known to be responsible for attention and arousal, and this may partially underpin some deficits in social behaviour.

Our understanding of anatomical differences in people with autistic-spectrum disorder, is based on mixed-gender or male samples.

To study regional grey-matter and white-matter differences in the brains of women with autistic-spectrum disorder.

We compared the brain anatomy of 14 adult women with autistic-spectrum disorder with 19 controls using volumetric magnetic resonance imaging and voxel-based morphometry Results Women with autistic-spectrum disorder had a smaller density bilaterally of grey matter in the frontotemporal cortices and limbic system, and of white matter in the temporal lobes (anterior) and pons. In contrast, they had a larger white-matter density bilaterally in regions of the association and projection fibres of the frontal, parietal, posterior temporal and occipital lobes, in the commissural fibres of the corpus callosum (splenium) and cerebellum (anterior lobe). Further, we found a negative relationship between reduced grey-matter density in right limbic regions and social communication ability.

Women with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms.

It has been suggested that people with psychopathic disorders lack empathy because they have deficits in processing distress cues (e.g. fearful facial expressions).

To investigate brain function when individuals with psychopathy and a control group process facial emotion.

Using event-related functional magnetic resonance imaging we compared six people scoring ⩾25 on the Hare Psychopathy Checklist–Revised and nine non-psychopathic healthy volunteers during an implicit emotion processing task using fearful, happy and neutral faces.

The psychopathy group showed significantly less activation than the control group in fusiform and extrastriate cortices when processing both facial emotions. However, emotion type affected response pattern. Both groups increased fusiform and extrastriate cortex activation when processing happy faces compared with neutral faces, but this increase was significantly smaller in the psychopathy group. In contrast, when processing fearful faces compared with neutral faces, the control group showed increased activation but the psychopathy group decreased activation in the fusiform gyrus.

People with psychopathy have biological differences from controls when processing facial emotion, and the pattern of response differs according to emotion type.

Obsessive–compulsive behaviours are common and disabling in autistic-spectrum disorders (ASD) but little is known about how they compare with those experienced by people with obsessive–compulsive disorder (OCD).

To make such a comparison.

A group of adults with high-functioning ASD (n=40) were administered the Yale–Brown Obsessive–Compulsive Scale and Symptom Checklist and their symptoms compared with a gender-matched group of adults with a primary diagnosis of OCD (n=45). OCD symptoms were carefully distinguished from stereotypic behaviours and interests usually displayed by those with ASD.

The two groups had similar frequencies of obsessive–compulsive symptoms, with only somatic obsessions and repeating rituals being more common in the OCD group. The OCD group had higher obsessive–compulsive symptom severity ratings but up to 50% of the ASD group reported at least moderate levels of interference from their symptoms.

Obsessions and compulsions are both common in adults with high-functioning ASD and are associated with significant levels of distress.

People with learning disability who exhibit challenging behaviour are frequently segregated from services and local teams are often reluctant to receive them back into their care. This situation is worse in those whose challenging behaviour includes a forensic history, but the difference between those labelled as challenging and those treated as offenders is not clear, and there is a lack of evidence about treatment effectiveness.

To test between-group differences in aggression and treatment outcome in people with learning disability and challenging behaviour, with and without a forensic history.

Clinical records of 86 former in-patients (45 offenders and 41 non-offenders) of a specialist unit were compared on measures of behavioural disturbance and placement outcome.

People in the offenders group were significantly less likely to be aggressive to others and to use weapons, but significantly more likely to harm themselves compared with the non-offenders group. Both groups had a significant reduction in their challenging behaviour during admission, and there was no significant difference in treatment outcome.

The negative reputation of people with learning disabilities who offend needs to be reconsidered.