Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

European Neuropsychopharmacology

Clozapine is the only licensed medication for treatment-resistant schizophrenia (TRS). Few predictors for variation in response to clozapine have been identified, but clozapine metabolism is known to influence therapeutic response and adverse side effects. Here, we expand on genome-wide studies of clozapine metabolism, previously focused on common genetic variation, by analysing whole-exome sequencing data from 2062 individuals with schizophrenia taking clozapine in the UK. We investigated whether rare genomic variation in genes and gene sets involved in the clozapine metabolism pathway influences plasma concentrations of clozapine metabolites, assessed through the longitudinal analysis of 6585 pharmacokinetic assays. We observed a statistically significant association between the burden of rare damaging coding variants (MAF ≤ 1 %) in gene sets broadly related to drug pharmacokinetics and …

Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for schizophrenia within complement genes will associate with structural changes in white matter microstructure within tracts innervating the frontal lobe. Our results show that risk alleles within the complement gene set, but also intergenic alleles, significantly predict axonal density in these white matter tracts. More specifically, risk alleles within the Major Histocompatibility Complex (MHC) region in chromosome 6 appeared to drive these association, although intergenic alleles mostly within chromosome 19 also show to play part. No significant associations were found for the orientation dispersion index. Our results suggest changes in axonal packing-but not in axonal coherence-determined by common risk alleles within the MHC genomic region, as a potential neurobiological mechanism for schizophrenia.

medRxiv

Predicted loss-of-function variants (pLoFs) are often associated with disease. For genes linked with monogenic diseases, we hypothesised that pLoFs present in apparently unaffected individuals may cluster in LoF-tolerant regions. We compared the distribution of pLoFs in ClinVar versus 454,773 individuals in UK Biobank and clustered the variants using Gaussian mixture models. We found that genes in which haploinsufficiency causes developmental disorders with incomplete penetrance were less likely to have a uniform pLoF distribution than other genes (P<2.2x10-6). In some cases (e.g., ARID1B and GATA6), pLoF variants in the first quarter of the gene could be rescued by an alternative translation start site and should not be reported as pathogenic. In other cases (e.g., ODC1), pathogenic pLoFs were clustered only at the end of the gene, consistent with a gain-of-function disease mechanism. Our results support the use of localised constraint metrics when interpreting variants.

The Journal of Pain

The current study aims to characterize brain morphology of pain as reported by small fiber neuropathy (SFN) patients with or without a gain-of-function variant involving the SCN9A gene and compare these with findings in healthy controls without pain. The Neuropathic Pain Scale was used in patients with idiopathic SFN (N = 20) and SCN9A-associated SFN (N = 12) to capture pain phenotype. T1-weighted, structural magnetic resonance imaging (MRI) data were collected in patients and healthy controls (N = 21) to 1) compare cortical thickness and subcortical volumes and 2) quantify the association between severity, quality, and duration of pain with morphological properties. SCN9A-associated SFN patients showed significant (P < .017, Bonferroni corrected) higher cortical thickness in sensorimotor regions, compared to idiopathic SFN patients, while lower cortical thickness was found in more functionally diverse …

Biological psychiatry

BackgroundCarriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.MethodsMagnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’s regional difference and global difference, were used to test for regional differences that diverge from the global difference.ResultsFor the 1q21.1 distal deletion carriers, cortical …

Neuropsychopharmacology

Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10–17 years old. Resting-state oscillatory activity and …

European Archives of Psychiatry and Clinical Neuroscience

Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study — the University of Bath's research portal Skip to main navigation Skip to search Skip to main content the University of Bath's research portal Home the University of Bath's research portal Logo Help & FAQ Home Profiles Research output Projects Datasets Student theses Equipment Research units Search by expertise, name or affiliation Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study Rachel Lees, William Lawn, Kat Petrilli, Amelia Brown, Katie Trinci, Anya Borissova, Shelan Ofori, Claire Mokrysz, H. Valerie Curran, Lindsey Hines, Tom Freeman Addiction and Mental Health Group (AIM) Department of Psychology Centre for 21st Century Public Health Tobacco Control Research Group (TCRG) University …

Deep Brain Stimulation

BackgroundDeep brain stimulation (DBS) is an effective intervention for refractory obsessive-compulsive disorder (OCD). Although treatment success is measured by a decrease in the severity of core symptoms, this procedure can have broader psychological and physical effects. The field regrettably still lacks knowledge and tools allowing an adequate understanding and assessment of the full range of experiences that accompany DBS treatment. We aimed to describe possible side effects of DBS treatment as experienced by patients, beyond specific changes in OCD core symptoms.MethodsWe interviewed 16 patients and 7 of their relatives from two independent cohorts, receiving stimulation in different anatomical locations. We conducted semi-structured interviews, then transcribed at verbatim. Inductive content analysis was performed to code and group common themes.ResultsWe categorized a variety of …

New genomic technologies have improved the speed and accuracy with which rare disease diagnoses can be made in individuals presenting with a phenotype. These advancements have led to enthusiasm for applying these technologies at the population level to identify individuals at increased genomic risk of disease, and for their application in common as well as rare diseases. The UK has seen two major initiatives launch in 2023 that explore population screening by use of genomics. In the Genomics England Newborn Genomes Programme (NGP; the Generations Study), actionable findings from wholegenome sequencing (WGS) will be communicated for more than 200 diseases in 100 000 participating newborn babies. 1 The UK’s Our Future Health (OFH) programme is recruiting up to 5 million adults via the National Health Service (NHS) for participation in research on common genetic variants, with plans to …

Research that examines processes transmitting risks from paternal postnatal depression (PND) to child development is limited. This study examines pathways from paternal PND to offspring development though paternal parenting confidence, warmth, and father-child conflict in the ALSPAC birth-cohort (n= 9,628). Adjusted models revealed evidence of total associations between paternal PND, offspring emotional symptoms, peer problems and hyperactivity, but not conduct problems. Indirect effects emerged from paternal PND to offspring emotional symptoms, hyperactivity and peer problems through the combination of all paternal parenting factors, with no evidence of direct effects. Specificity analyses revealed indirect effects through paternal parenting confidence and father-child conflict. Targeted intervention to increase paternal parenting confidence and decrease father-child conflict may improve outcomes in children of depressed fathers.

Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification, and holds great potential in mental disorders. However, several important factors are needed to transform current practice into a “precision psychiatry” framework. Most important are (1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, (2) the development and validation of advanced analytical tools for stratification and prediction, and (3) the development of clinically useful management platforms for patient monitoring that can be integrated into healthcare systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements – well-powered samples from large biobanks, integrated with electronic health records and health registry data using novel artificial intelligence algorithms – to predict …

Habituation to pain is a fundamental learning process and important adaption. Yet, a comprehensive review of the current state of the field is lacking. Through a systematic search, 63 studies were included. Results address habituation to pain in healthy individuals based on self-report, electroencephalography, or functional magnetic resonance imaging. Our findings indicate a large variety in methods, experimental settings, and contexts, making habituation a ubiquitous phenomenon. Habituation to pain based on self-report studies shows a large influence of expectations, as well as the presence of individual differences. Furthermore, widespread neural effects, with sometimes opposing effects in self-report measures, are noted. Electroencephalography studies showed habituation of the N2-P2 amplitude, whereas functional magnetic resonance imaging studies showed decreasing activity during painful repeated …

Archives of Physical Medicine and Rehabilitation

ObjectiveTo evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints.DesignProspective, multicenter cohort study.SettingSix Dutch hospitals.Participants205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205).InterventionsNot applicable.Main Outcome MeasuresNine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from …

Clinical Neurology and Neurosurgery

BACKGROUNDNeurological complications in COVID-19 patients admitted to an intensive care unit (ICU) have been previously reported. As the pandemic progressed, therapeutic strategies were tailored to new insights. This study describes the incidence, outcome, and types of reported neurological complications in invasively mechanically ventilated (IMV) COVID-19 patients in relation to three periods during the pandemic.METHODSIMV COVID-19 ICU patients from the Dutch Maastricht Intensive Care COVID (MaastrICCht) cohort were included in a single-center study (March 2020 – October 2021). Demographic, clinical, and follow-up data were collected. Electronic medical records were screened for neurological complications during hospitalization. Three distinct periods (P1, P2, P3) were defined, corresponding to periods with high hospitalization rates. ICU survivors with and without reported neurological …

European Neuropsychopharmacology

Background: Schizophrenia (SZ) is a highly heritable disorder associated with increased rates of cortical thinning across the lifespan [1, 2]. Genetic factors play a significant role in changes in cortical thickness in neurotypical individuals, with studies reporting high heritability for most brain regions [3, 4]. Regional progressive cortical thinning after onset of psychotic symptoms has been systematically described [5]. Here we studied functional enrichment, transcriptomic signatures, and genetic risk variation of accelerated regional cortical thinning (ACT) as observed in SZ compared to healthy controls (HC).Methods: MRI data was obtained from participants with SZ and healthy controls (HC) from Utrecht, The Netherlands (NSZ= 169 and NHC= 298, MRI scans= 1087, age range 16-70 years). All subjects had baseline and follow-up scans (3.95–4.12 years). ACT was calculated for 68 regions of Freesurfer's Desikan …

BMC psychiatry

BackgroundClozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost …

Addiction

Background: High-potency cannabis has been associated with increased risk of psychosis, but a lack of prospective data hinders understanding of causality in this relationship.Aims: Combine prospective report of cannabis use with retrospective report of potency to infer the potency of cannabis used in adolescence and explore whether use of cannabis, and the use of high-potency cannabis, in adolescence is associated with incident psychotic experiences.Design: Population-based birth cohort study.Setting: United KingdomParticipants: N= 5570 participants who reported on any cannabis use (yes/no) age 16 and 18 years, and N= 1560 participants from this group who also retrospectively reported on cannabis potency.Measurements: In questionnaires at ages 16 and 18 individuals self-reported lifetime cannabis use, and at age 24, participants reported the type of cannabis they most commonly used in the whole time since first using cannabis. Psychotic experiences were assessed at age 24 years using the semi-structured Psychosis-Like Symptom Interview, with incident defined as new-onset occurring between ages 19 and 24 years.Findings: Results indicated use of high-potency cannabis at age 16 or 18 is associated with twice the likelihood of experiencing incident psychotic experiences from age 19-24 (Odds Ratio 2.15, 95% Confidence Intervals 1.13-4.06). There was less evidence for an effect of any cannabis use on incident psychotic experiences (Odds Ratio 1.45, 95% Confidence Intervals 0.94-2.12).Conclusions: This work contributes to a growing body of evidence indicating that use of high-potency cannabis is associated with …

Genetics in Medicine Open

PurposeStructural variants such as multi-exon deletions and duplications are an important cause of disease, but are often overlooked in standard exome/genome sequencing analysis. We aimed to evaluate the detection of copy number variants (CNVs) from exome sequencing (ES) in comparison to genome-wide low-resolution and exon-resolution chromosomal microarrays (CMA), and to characterise the properties of de novo CNVs in a large clinical cohort.MethodsWe performed CNV detection using ES of 9,859 parent-offspring trios in the Deciphering Developmental Disorders (DDD) study, and compared them to CNVs detected from exon-resolution array comparative genomic hybridization (aCGH) in 5,197 probands from the DDD study.ResultsIntegrating calls from multiple ES-based CNV algorithms using random forest machine learning generated a higher quality dataset than using individual algorithms. Both …

Scientific reports

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in …

Nature Genetics

Rare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2-5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants. Among carriers of rare DD variants, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without a clinical diagnosis. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may then influence whether an individual reaches the threshold for clinical disease.

Psychological Medicine

Background Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. Methods Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. Results Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and …

Psychological Medicine

BackgroundCardiovascular disease (CVD) is excessively prevalent and premature in bipolar disorder (BD), even after controlling for traditional cardiovascular risk factors. The increased risk of CVD in BD may be subserved by microvascular dysfunction. We examined coronary microvascular function in relation to youth BD.MethodsParticipants were 86 youth, ages 13–20 years (n = 39 BD, n = 47 controls). Coronary microvascular reactivity (CMVR) was assessed using quantitative T2 magnetic resonance imaging during a validated breathing-paradigm. Quantitative T2 maps were acquired at baseline, following 60-s of hyperventilation, and every 10-s thereafter during a 40-s breath-hold. Left ventricular structure and function were evaluated based on 12–15 short- and long-axis cardiac-gated cine images. A linear mixed-effects model that controlled for age, sex, and body mass index assessed for between-group …

Psychological medicine

BackgroundSuicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.MethodsData come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this …

Psychological Medicine

BackgroundMild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown.MethodsChildren with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or …

Psychological Medicine

When this article was published in Psychological Medicine, it omitted to capitalise ‘Mini International Neuropsychiatric Interview’in its title. This has now been updated online. The author apologises for this error.

Psychological Medicine

BackgroundIncidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.MethodsWe used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational …

Psychological Medicine

BackgroundThe relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms.MethodsSeven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale.ResultsPatients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood …

Psychological Medicine

BackgroundCerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.MethodsLongitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence …

Psychological medicine

BackgroundYouth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality.MethodsData from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11–14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and …

Psychological medicine

BackgroundSchizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation.MethodsWe compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI.ResultsPwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group …

Psychological Medicine

BackgroundAccumulating 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.MethodA 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.ResultsWe 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 …

Psychological Medicine

BackgroundThe age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis.MethodsThe analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12–17 years old; 411 early-middle adults, 18–54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively.ResultsWe found shared FC reductions …

Psychological Medicine

BackgroundScreen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.MethodsWe examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.ResultsInfant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and …

Psychological Medicine

BackgroundTo address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies.MethodsFour primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy, and siblings) born between 1 January 1990 and 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured. The NDD incidence rate among (1) children exposed during or outside of pregnancy and (2) siblings discordant for exposure in …

Psychological Medicine

BackgroundChildbirth may be a traumatic experience and vulnerability to posttraumatic stress disorder (PTSD) may increase the risk of postpartum depression (PPD). We investigated whether genetic vulnerability to PTSD as measured by polygenic score (PGS) increases the risk of PPD and whether a predisposition to PTSD in PPD cases exceeds that of major depressive disorder (MDD) outside the postpartum period.MethodsThis case-control study included participants from the iPSYCH2015, a case-cohort of all singletons born in Denmark between 1981 and 2008. Restricting to women born between 1981 and 1997 and excluding women with a first diagnosis other than depression (N = 22 613), 333 were identified with PPD. For each PPD case, 999 representing the background population and 993 with MDD outside the postpartum were matched by calendar year at birth, cohort selection, and age. PTSD PGS …

Psychological Medicine

BackgroundPost-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit.MethodsData came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively.ResultsCompared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved …

Psychological Medicine

BackgroundVery-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores.MethodsIn this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated …

Psychological Medicine

BackgroundFatigue is a central feature of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), but many ME/CFS patients also report comorbid pain symptoms. It remains unclear whether these symptoms are related to similar or dissociable brain networks. This study used resting-state fMRI to disentangle networks associated with fatigue and pain symptoms in ME/CFS patients, and to link changes in those networks to clinical improvements following cognitive behavioral therapy (CBT).MethodsRelationships between pain and fatigue symptoms and cortico-cortical connectivity were assessed within ME/CFS patients at baseline (N = 72) and after CBT (N = 33) and waiting list (WL, N = 18) and compared to healthy controls (HC, N = 29). The analyses focused on four networks previously associated with pain and/or fatigue, i.e. the fronto-parietal network (FPN), premotor network (PMN), somatomotor …

Psychological Medicine

BackgroundThere is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI).MethodsPatients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks.ResultsPatients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho …

Psychological medicine

BackgroundSchizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.MethodsWe addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were …