Search

SUMMARY On average, 49–63% of people with intellectual disabilities and/or autism spectrum disorder (ASD) are prescribed psychotropic medications to treat psychopathology, including psychiatric illness, behaviours that challenge and the core symptoms and associated behaviours of these developmental disorders. In many cases, psychotropics, particularly antipsychotics, are used off-label without a proper indication, particularly to manage behaviours that challenge. The RCTs show moderate evidence supporting the efficacy of low-dose risperidone and some preliminary evidence for aripiprazole in treating behaviours that challenge among children with ASD and/or intellectual disabilities. The RCT-based evidence for the other psychotropics is equivocal, so no definitive conclusions can be made on their efficacy. Polypharmacy and the use of high doses of antipsychotics are prevalent in this population, leading to the risk of adverse events and drug–drug interactions. Despite various national and international guidelines, and government initiatives encouraging reduced psychotropic use, there is little evidence of this happening; on the contrary, the use of antidepressants, mood stabilisers and benzodiazepines may be increasing. A concerted multi-agency effort is urgently needed to address this significant public health concern of the overmedication of people with intellectual disabilities and/or ASD.

Background Euthanasia review committees (Regionale Toetsingscommissies Euthanasie, RTE) scrutinise all Dutch cases of euthanasia and physician-assisted suicide (EAS) to review whether six legal ‘due care’ criteria are met, including ‘unbearable suffering without prospect of improvement’. There are significant complexities and ethical dilemmas if EAS requests are made by people with intellectual disabilities or autism spectrum disorders (ASD). Aims To describe the characteristics and circumstances of people with intellectual disabilities and/or ASD who were granted their EAS request; investigate the main causes of suffering that led to the EAS request; and examine physicians’ response to the request. Method The online RTE database of 927 EAS case reports (2012–2021) was searched for patients with intellectual disabilities and/or ASD (n = 39). Inductive thematic content analysis was performed on these case reports, using the framework method. Results Factors directly associated with intellectual disability and/or ASD were the sole cause of suffering described in 21% of cases and a major contributing factor in a further 42% of cases. Reasons for the EAS request included social isolation and loneliness (77%), lack of resilience or coping strategies (56%), lack of flexibility (rigid thinking or difficulty adapting to change) (44%) and oversensitivity to stimuli (26%). In one-third of cases, physicians noted there was ‘no prospect of improvement’ as ASD and intellectual disability are not treatable. Conclusions Examination of societal support for suffering associated with lifelong disability, and debates around the acceptability of these factors as reasons for granting EAS, are of international importance.

Hypothalamic-pituitary adrenal (HPA)axis dysregulation has long been implicated in stress-related disorders such as major depression and post-traumatic stress disorder. Glucocorticoids (GCs) are released from the adrenal glands as a result of HPA-axis activation. The release of GCs is implicated with several neurobiological changes that are associated with negative consequences of chronic stress and the onset and course of psychiatric disorders. Investigating the underlying neurobiological effects of GCs may help to better understand the pathophysiology of stress-related psychiatric disorders. GCs impact a plethora of neuronal processes at the genetic, epigenetic, cellular, and molecular levels. Given the scarcity and difficulty in accessing human brain samples, 2D and 3D in vitro neuronal cultures are becoming increasingly useful in studying GC effects. In this review, we provide an overview of in vitro studies investigating the effects of GCs on key neuronal processes such as proliferation and survival of progenitor cells, neurogenesis, synaptic plasticity, neuronal activity, inflammation, genetic vulnerability, and epigenetic alterations. Finally, we discuss the challenges in the field and offer suggestions for improving the use of in vitro models to investigate GC effects.

Background Little is known about factors that may explain the association between depressive symptoms and poor labour market participation (LMP). The aim of this study is to examine the mediation and interaction effects of social support on the association between depressive symptoms and LMP. Methods Data were used from 985 participants (91% of the initial cohort) of the Northern Swedish Cohort, a longitudinal study of Swedish participants followed from adolescence throughout adulthood. Depressive symptoms were measured at age 16, social support at age 21 and LMP from age 30 to 43. Poor LMP was defined as being unemployed for a total of 6 months or more between the ages of 30 and 43. A four-way decomposition approach was applied to identify direct, mediation and interaction effects, together and separately. Results Both depressive symptoms during adolescence and social support at young adulthood were associated with poor LMP [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.17–2.47 and OR = 2.56, 95% CI 1.78-3.68 respectively]. The association between depressive symptoms and poor LMP was partially mediated by a lack of social support. No interaction effect of a lack of social support was found. Conclusion The results suggest that depressive symptoms influence not only later LMP but also the intermediary level of social support, and in turn influencing later LMP. Recommendations for public health are to detect and treat depressive symptoms at an early stage and to focus on the development of social skills, facilitating the increased availability of social support, thereby improving future LMP.

Childhood trauma (CT) has been linked to increased risk for psychosis. Moreover, CT has been linked to psychosis phenotypes such as impaired cognitive and sensory functions involved in the detection of novel sensory stimuli. Our objective was to investigate if CT was associated with changes in hippocampal and superior temporal gyrus functional activation and connectivity during a novelty detection task. Fifty-eight young adults were assigned to High-CT (n = 28) and Low-CT (n = 24) groups based on their scores on the childhood trauma questionnaire (CTQ) and underwent functional Magnetic Resonance Imaging during an auditory oddball task (AOT). Relative to the Low CT group, High CT participants showed reduced functional activation in the left hippocampus during the unpredictable tone condition of the AOT. Furthermore, in the High CT group, psychophysiological interaction analysis revealed hypoconnectivity between the hippocampus and temporal and medial regions. The present study indicates both altered hippocampal activation and hippocampal-temporal-prefrontal connectivity during novelty detection in individuals that experienced CT, similarly to that reported in psychosis risk populations. Early stressful experiences and environments may alter hippocampal function during salient events, mediating the relationship between childhood trauma and psychosis risk.

Suicide is a worldwide health crisis. We aimed to identify genetic risk variants associated with suicide death and suicidal behavior. Meta-analysis for suicide death was performed using 3765 cases from Utah and matching 6572 controls of European ancestry. Meta-analysis for suicidal behavior using data across five cohorts (n = 8315 cases and 256,478 psychiatric or populational controls of European ancestry) was also performed. One locus in neuroligin 1 (NLGN1) passing the genome-wide significance threshold for suicide death was identified (top SNP rs73182688, with p = 5.48 × 10−8 before and p = 4.55 × 10−8 after mtCOJO analysis conditioning on MDD to remove genetic effects on suicide mediated by MDD). Conditioning on suicidal attempts did not significantly change the association strength (p = 6.02 × 10−8), suggesting suicide death specificity. NLGN1 encodes a member of a family of neuronal cell surface proteins. Members of this family act as splice site-specific ligands for beta-neurexins and may be involved in synaptogenesis. The NRXN-NLGN pathway was previously implicated in suicide, autism, and schizophrenia. We additionally identified ROBO2 and ZNF28 associations with suicidal behavior in the meta-analysis across five cohorts in gene-based association analysis using MAGMA. Lastly, we replicated two loci including variants near SOX5 and LOC101928519 associated with suicidal attempts identified in the ISGC and MVP meta-analysis using the independent FinnGen samples. Suicide death and suicidal behavior showed positive genetic correlations with depression, schizophrenia, pain, and suicidal attempt, and negative genetic correlation with educational attainment. These correlations remained significant after conditioning on depression, suggesting pleiotropic effects among these traits. Bidirectional generalized summary-data-based Mendelian randomization analysis suggests that genetic risk for the suicidal attempt and suicide death are both bi-directionally causal for MDD.

Background: Many people who enter prison have recently used drugs in the community, a substantial portion of whom will continue to do so while incarcerated. To date, little is known about what factors may contribute to the continuation of drug use during imprisonment. Methods: Self-reported data were collected from a random sample of 1326 adults (123 women) incarcerated across 15 prisons in Belgium. Multivariate regression was used to investigate associations between in-prison drug use and sociodemographic background, criminological profile, drug-related history, and mental health among participants who reported pre-prison drug use. Results: Of all 1326 participants, 719 (54%) used drugs in the 12 months prior to their incarceration and 462 (35%) did so while in prison. There was a strong association between drug use before and during imprisonment (OR = 6.77, 95% CI 5.16–8.89). Of those who recently used drugs in the community, half (52%) continued to do so while incarcerated. Factors independently associated with continuation (versus cessation) were young age, treatment history, polydrug use, and poor mental health. In a secondary analysis, initiation of drug use while in prison was further related to incarceration history and low education. Conclusion: Persistence of drug use following prison entry is common. People who continue to use drugs inside prison can be differentiated from those who discontinue in terms of drug-related history and mental health. Routine screening for drug use and psychiatric morbidity on admission to prison would allow for identifying unmet needs and initiating appropriate treatment.

BACKGROUND: Children at familial high-risk of schizophrenia and bipolar disorder have an elevated prevalence of mental disorders but studies of children within a narrow age range are lacking and there are few conjoint studies of these two groups. Knowledge on their mental health is important for prevention and early intervention.METHODS: The authors examined mental disorders and global functioning in children at familial high-risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP) compared with population-based controls. In a longitudinal cohort study, 450 children (FHR-SZ, n = 171; FHR-BP, n = 104; controls, n = 175), were assessed for Axis I disorders at baseline and four-year follow-up (mean age 11.9, SD 0.2) with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children and for global functioning with Children's Global Assessment Scale.RESULTS: Cumulative incidence of Any Axis I disorder was elevated by age 11 in children at FHR-SZ (54.4%, OR 3.0, 95% CI 1.9-4.7, p CONCLUSIONS: Children at FHR-SZ and FHR-BP have an elevated prevalence of mental disorders and poorer functioning than controls. Vulnerability in children at FHR manifests early and remains stable throughout childhood. Early attention toward their mental health and identification of those in need of intervention is warranted.

This cross-sectional study aimed to evaluate depression and anxiety symptoms of the children/grandchildren of COVID-19 patients, children/grandchildren of healthcare workers who have not infected COVID-19, and children/grandchildren of the control group. Parent and children’s perception about COVID-19–related stigma is also investigated and compared between groups. The perception about COVID-19–related stigma between different age and gender groups among children also investigated and compared. The mental health of the 71 participants aged 6–18 years was evaluated via a telemedicine-based semi-structured interview between March and April 2020. Children’s Depression Inventory (CDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED), and COVID-19–Related Stigma Form were administered to the participants. A significant negative correlation was found between age and separation anxiety disorder ( p = .005) and a significant positive correlation was found between age and generalized anxiety disorder ( p = .035) in the SCARED-Child report. Generalized anxiety disorder was found to be higher in females compared to males. A significant difference was found between the groups of parents in the COVID-19–Related Stigma Form. Patients infected with COVID-19, healthcare workers, and the control group have different perceptions about COVID-19–related stigma. The age of the children have an impact on stigma perceptions. Anxiety symptoms of children affected by age and gender. Future studies are recommended to determine the other factors associated with perceptions about COVID-19–related stigma among children and parents.

BACKGROUND: Altered functional brain connectivity has been proposed as an intermediate phenotype between genetic risk loci and clinical expression of schizophrenia. Genetic high-risk groups of healthy subjects are particularly suited for the investigation of this proposition because they can be tested in the absence of medication or other secondary effects of schizophrenia. METHODS: Here, we applied dynamic functional connectivity analysis to functional magnetic resonance imaging data to reveal the reconfiguration of brain networks during a cognitive task. We recruited healthy carriers of common risk variants using the recall-by-genotype design. We assessed 197 individuals: 99 individuals (52 female, 47 male) with low polygenic risk scores (schizophrenia risk profile scores [SCZ-PRSs]) and 98 individuals (52 female, 46 male) with high SCZ-PRSs from both tails of the SCZ-PRS distribution from a genotyped population cohort, the Avon Longitudinal Study of Parents and Children (N = 8169). We compared groups both on conventional brain activation profiles, using the general linear model of the experiment, and on the neural flexibility index, which quantifies how frequent a brain region's community affiliation changes over experimental time. RESULTS: Behavioral performance and standard brain activation profiles did not differ significantly between groups. High SCZ-PRS was associated with reduced flexibility index and network modularity across n-back levels. The whole-brain flexibility index and that of the frontoparietal working memory network was associated with n-back performance. We identified a dynamic network phenotype related to high SCZ-PRS. CONCLUSIONS: Such neurophysiological markers can become important for the elucidation of biological mechanisms of schizophrenia and, particularly, the associated cognitive deficit.

Purpose Lesbian, gay, and bisexual (LGB) individuals, and LB women specifically, have an increased risk for psychiatric morbidity, theorized to result from stigma-based discrimination. To date, no study has investigated the mental health disparities between LGB and heterosexual AQ1individuals in a large cross-national population-based comparison. The current study addresses this gap by examining differences between LGB and heterosexual participants in 13 cross-national surveys, and by exploring whether these disparities were associated with country-level LGBT acceptance. Since lower social support has been suggested as a mediator of sexual orientation-based differences in psychiatric morbidity, our secondary aim was to examine whether mental health disparities were partially explained by general social support from family and friends. Methods Twelve-month prevalence of DSM-IV anxiety, mood, eating, disruptive behavior, and substance disorders was assessed with the WHO Composite International Diagnostic Interview in a general population sample across 13 countries as part of the World Mental Health Surveys. Participants were 46,889 adults (19,887 males; 807 LGB-identified). Results Male and female LGB participants were more likely to report any 12-month disorder (OR 2.2, p Conclusion These results provide cross-national evidence for an association between sexual minority status and psychiatric morbidity, and highlight that for women, but not men, this association was partially mediated by perceived openness with family. Future research into individual-level and cross-national sexual minority stressors is needed.

Background: This systematic review evaluated whether there is evidence for (i) increased emotional stress levels, and (ii) a different biological stress response or rhythm [i.e., cortisol stress response, diurnal rhythm, or cortisol awakening response (CAR)] in individuals with autism spectrum disorder (ASD) relative to controls. Thirdly, the evidence for an association between emotional and biological stress in ASD was reviewed.Method: MEDLINE, Cochrane Library, and SAGE journals were searched until December 2020. In this review, there were no limitations regarding age, sex, or intelligence quotient. Studies were only reviewed if results were compared with controls without a developmental disorder. Only salivary cortisol was considered as biological stress measure.Results: Thirty-one studies were reviewed. Significantly higher self-and parent-reported emotional stress levels were found in individuals with ASD compared to controls. Regarding biological stress, the few studies in adults reported comparable cortisol stress responses and rhythms between both groups. In children/adolescents with ASD relative to controls, an increased, blunted, or similar cortisol stress response was reported, whereas the CAR did not differ in most studies, and diurnal rhythm was described as blunted or similar. Most studies found no significant association between parent-reported emotional stress and biological stress in ASD.Conclusions: Current findings suggest that heightened emotional stress is a clinically significant factor in ASD. To unravel the cortisol response and rhythm, research in specific subgroups within the ASD spectrum is warranted, aiming at a higher frequency of cortisol measurements, prefer-ably combined with momentary emotional stress measurements.

Background Studies often evaluate mental health and well-being in association with individual health behaviours although evaluating multiple health behaviours that co-occur in real life may reveal important insights into the overall association. Also, the underlying pathways of how lifestyle might affect our health are still under debate. Here, we studied the mediation of different health behaviours or lifestyle factors on mental health and its effect on core markers of ageing: telomere length (TL) and mitochondrial DNA content (mtDNAc). Methods In this study, 6054 adults from the 2018 Belgian Health Interview Survey (BHIS) were included. Mental health and well-being outcomes included psychological and severe psychological distress, vitality, life satisfaction, self-perceived health, depressive and generalised anxiety disorder and suicidal ideation. A lifestyle score integrating diet, physical activity, smoking status, alcohol consumption and BMI was created and validated. On a subset of 739 participants, leucocyte TL and mtDNAc were assessed using qPCR. Generalised linear mixed models were used while adjusting for a priori chosen covariates. Results The average age (SD) of the study population was 49.9 (17.5) years, and 48.8% were men. A one-point increment in the lifestyle score was associated with lower odds (ranging from 0.56 to 0.74) for all studied mental health outcomes and with a 1.74% (95% CI: 0.11, 3.40%) longer TL and 4.07% (95% CI: 2.01, 6.17%) higher mtDNAc. Psychological distress and suicidal ideation were associated with a lower mtDNAc of − 4.62% (95% CI: − 8.85, − 0.20%) and − 7.83% (95% CI: − 14.77, − 0.34%), respectively. No associations were found between mental health and TL. Conclusions In this large-scale study, we showed the positive association between a healthy lifestyle and both biological ageing and different dimensions of mental health and well-being. We also indicated that living a healthy lifestyle contributes to more favourable biological ageing.

22q11.2 deletion syndrome (22q11DS) contributes dramatically increased genetic risk for psychopathology, and in particular schizophrenia. Sleep disorders, including obstructive sleep apnea (OSA), are also highly prevalent, making 22q11DS a unique model to explore their impact on psychosis vulnerability. Still, the contribution of sleep disturbances to psychosis vulnerability remains unclear.We characterized the sleep phenotype of 69 individuals with 22q11DS and 38 healthy controls with actigraphy and sleep questionnaires. Psychiatric symptoms were measured concomitantly with the baseline sleep assessment and at longitudinal follow-up, 3.58±0.85 years later. We used a novel multivariate partial-least-square-correlation (PLSC) approach to identify sleep patterns combining objective and subjective variables, which correlated with psychiatric symptoms. We dissected longitudinal pathways linking sleep disturbances to psychosis, using multi-layer-network-analysis.22q11DS was characterized by a non-restorative sleep pattern, combining increased daytime fatigue despite longer sleep duration. Non-restorative sleep combined with OSA symptoms correlated with both emotional and psychotic symptoms. Moreover, a sleep pattern evocative of OSA predicted longitudinal worsening of positive and negative symptoms, by accentuating the effects of emotional dysregulation. These results suggest that sleep disturbances could significantly increase psychosis risk, along an affective pathway. If confirmed, this suggests that systematic screening of sleep quality could mitigate psychosis vulnerability in 22q11DS.

ObjectiveTo examine the prevalence and risk factors for medically treated anxiety and depression disorders among men and women with musculoskeletal strain or sprain work injury in British Columbia, Canada.MethodsA retrospective population-based cohort of accepted workers’ compensation lost-time claims from 2000 to 2013 was constructed using linked administrative health data. Anxiety and depression disorders were identified using diagnoses from physician, hospital and pharmaceutical records. The 1-year period prevalence was estimated for the year before and the year after injury. Sociodemographic, clinical and work-related risk factors for prevalent and new onset anxiety and depression disorders were examined using multinomial regression.Results13.2% of men and 29.8% of women had medically treated anxiety, depression or both in the year before injury. Only a slight increase (~2%) in the prevalence of these disorders was observed in the year after injury. Somatic and mental comorbidities were both strong risk factors for pre-existing and new onset anxiety and depression for both men and women, but these relationships were stronger for men.ConclusionAnxiety and depression disorders including those from prior to injury are common in workers with musculoskeletal strain or sprain and are associated with a complicated clinical profile. Gender-sensitive and sex-sensitive mental healthcare is an important consideration for work disability management.

This study investigated adolescents’ Quality of Life and mental health needs during the first weeks in a closed institution for mandatory care and treatment to inform (gender-specific) rehabilitation. Questionnaires concerning socio-demographic variables, Quality of Life and mental health needs were administered (n ¼ 182; 90 boys and 92 girls; mean age ¼ 16.2). Given the high prevalence of mental health needs in this study population and their significant negative correlation with QoL, we argue for a holistic view on rehabilitation and to broaden treatment aims in youth forensic care by including not only determinants of recidivism but also determinants of QoL.

Parent relationship satisfaction and parental reflective functioning (PRF) are significant factors in the transition to first-time parenting and are likely to affect a child’s later wellbeing. However, little is known about their joint longitudinal effects from pregnancy onward. Starting in the prenatal period, this follow-up study of 1016 Finnish first-time parents (358 fathers and 658 mothers at baseline) examined the stability and the reciprocal associations between relationship satisfaction and PRF in predicting child behavioral problems (CBCL) at age 2. First, the results of the random-intercept cross-lagged panel models showed that both relationship satisfaction and PRF were stable from pregnancy onward for both mothers and fathers, with the exception of mothers’ prenatal PRF. Second, there were significant reciprocal associations between low prenatal PRF and low relationship satisfaction at age 1, and vice versa. Third, for both mothers and fathers, a low level of relationship satisfaction, but not PRF, predicted consistently higher levels of child behavioral problems at age 2. These results suggest that parent relationship satisfaction and PRF are stable but largely independent parental factors during the transition to parenthood. In addition, our results highlight the significant role of parent relationship satisfaction in predicting toddler behavior problems, which indicates the relevance of early relationship-orientated help for first-time parents.

Emotional and behavioural problems (EBP) have a negative impact on various life domains of adolescents. Receiving care for EBP may improve the functioning of adolescents with EBP, but evidence on long-term outcomes in real-life settings is lacking. We, therefore, investigated self-reported functioning in different life domains of adolescents with various EBP, and the role of care during a three-year period. We used data from the TAKECARE study, which consist of a care and community cohort. We followed adolescents aged 12 and over (n = 733) during 3 years over five assessment rounds. Using the Strengths and Difficulties Questionnaire, self-reported functioning was measured in four life domains: home life, friendships, classroom learning and leisure activities. We categorized the respondents into four groups: (1) adolescents without emotional and behavioural problems (n = 298); (2) adolescents with emotional problems (n = 192); (3) adolescents with behavioural problems (n = 80); and (4) adolescents with both emotional and behavioural problems (n = 163). The development of functioning over time was analyzed using longitudinal ordinal (probit) regression analyses. Adolescents with both emotional and behavioural problems reported poorer functioning at baseline in all domains and adolescents who received care reported poorer functioning at baseline compared to adolescents who did not receive care. Regarding the change in functioning during the 3 years, adolescents who received care showed improved functioning in all domains. We found improved functioning after care, even if the problems may not have been solved. Psychosocial care can contribute to the functioning of adolescents with EBP, which can have major effects on their future life.

Twenty-first century urbanization poses increasing challenges for mental health. Epidemiological studies have shown that mental health problems often accumulate in urban areas, compared to rural areas, and suggested possible underlying causes associated with the social and physical urban environments. Emerging work indicates complex urban effects that depend on many individual and contextual factors at the neighbourhood and country level and novel experimental work is starting to dissect potential underlying mechanisms. This review summarizes findings from epidemiology and population-based studies, neuroscience, experimental and experience-based research and illustrates how a combined approach can move the field towards an increased understanding of the urbanicity-mental health nexus.

BackgroundAlthough early results of bariatric surgery are beneficial for most patients, some patients regain weight later. Cognitive behavioral therapy (CBT) has been suggested as a way to improve patients’ psychological health and maintaining weight loss in the longer term. The added value of preoperative CBT to bariatric surgery was examined. Pre- and posttreatment and 1-year follow-up data are presented.MethodsIn a multi-center randomized controlled trial, CBT was compared to a treatment-as-usual (TAU) control group. Measurements were conducted pre- and posttreatment/pre-surgery (T0 and T1) and at 1-year post-surgery (T2). Patients in the intervention group received 10 individual, weekly sessions of preoperative CBT focused on modifying thoughts and behaviors regarding eating behavior, physical exercise, and postoperative life style. Outcome measures included weight change, eating behavior, eating disorders, depression, quality of life, and overall psychological health.ResultsThough no significant differences between conditions were found per time point, in the CBT, condition scores on external eating, emotional eating, depressive symptoms, and psychological distress decreased significantly more over time between pre- (T0) and posttreatment (T1) pre-surgery compared to TAU. No significant time x condition differences were found at 1-year post-surgery (T2).ConclusionsCompared to TAU, preoperative CBT showed beneficial effects on eating behavior and psychological symptoms only from pretreatment to posttreatment/pre-surgery, but not from pre-surgery to 1-year post-surgery. Preoperative CBT does not seem to contribute to better long-term outcomes post-surgery. Recent studies suggest that the optimal time to initiate psychological treatment may be early in the postoperative period, before significant weight regain has occurred.Trial Registrationhttps://www.trialregister.nlIdentifier: Trial NL3960.

Hypothalamic-pituitary adrenal (HPA)axis dysregulation has long been implicated in stress-related disorders such as major depression and post-traumatic stress disorder. Glucocorticoids (GCs) are released from the adrenal glands as a result of HPA-axis activation. The release of GCs is implicated with several neurobiological changes that are associated with negative consequences of chronic stress and the onset and course of psychiatric disorders. Investigating the underlying neurobiological effects of GCs may help to better understand the pathophysiology of stress-related psychiatric disorders. GCs impact a plethora of neuronal processes at the genetic, epigenetic, cellular, and molecular levels. Given the scarcity and difficulty in accessing human brain samples, 2D and 3D in vitro neuronal cultures are becoming increasingly useful in studying GC effects. In this review, we provide an overview of in vitro studies investigating the effects of GCs on key neuronal processes such as proliferation and survival of progenitor cells, neurogenesis, synaptic plasticity, neuronal activity, inflammation, genetic vulnerability, and epigenetic alterations. Finally, we discuss the challenges in the field and offer suggestions for improving the use of in vitro models to investigate GC effects.

The risk for major depressive disorder (MDD) is considerably increased in young adults with attention-deficit/hyperactivity disorder (ADHD) but underlying mechanisms are poorly understood. This review explores ADHD-specific neurocognitive impairments as possible underlying mechanisms for ADHD-depression comorbidity. Two systematic literature searches were conducted in EBSCOhost, PubMED, and Cochrane Reviews databases according to PRISMA guidelines. The first search identified 18 meta-analyses of cross-sectional and longitudinal studies on cognitive dysfunctions in MDD across the lifespan. The second search identified six original studies on reaction time variability in MDD. During acute depression, children and adults showed cognitive deficits that overlapped with some of the ADHD-related impairments. Findings from remitted patients, high-risk individuals, and few prospective studies suggest that a subset of these shared impairments, specifically executive dysfunctions (selective attention, verbal fluency, working memory) and long-term memory problems, are candidate pre-existing risk markers of depression. We discuss if and how these specific neurocognitive mechanisms may mediate developmental pathways from ADHD to depression. If replicated by longitudinal studies, these findings may guide future prevention strategies.

Objective Binge-eating disorder (BED) was established as a diagnosis in 2013 with the DSM-5 and has been included in the ICD-11 in 2018. In adulthood, BED is prevalent and correlated with somatic and mental health problems. Less is known about BED in adolescence, although this age period could represent a window of opportunity for early intervention. This study aimed to investigate the 1-year prevalence, correlates, and impact of BED symptoms in a community sample of adolescents.Method We included 1,404 girls and 1,105 boys from the 16-years-follow-up of the Copenhagen Child Cohort study, CCC2000. The adolescents self-reported on BED symptoms, weight-status, body perception, mental health problems, and self-rated impact of food and weight-related thoughts and behaviors. Information about socio-economic factors and hospital diagnosed psychiatric disorders were obtained from national registries.Results A total of 8.5% reported weekly overeating with loss of control (10.9% of girls, 4.8% of boys), and 2.6% (3.6% of girls, 1.2% of boys) reported symptoms consistent with BED according to the DSM-5. Regardless of sex, BED was correlated with concurrent overweight, body-dissatisfaction, low self-esteem, and mental health problems, especially emotional, but also with problems of behavior, inattention, and peer-relations, and with high self-rated impact on everyday life. Immigrant background and lower socio-economy were potential risk factors for BED in boys in this sample.Discussion BED was prevalent and correlated with mental health problems and overall impact among adolescents in this community sample, indicating the need for clinical attention and intervention towards binge-eating disorder in the adolescent period.

Background Children born very preterm (VPT; Methods Dynamic functional connectivity was extracted by using the innovation-driven co-activation patterns framework in VPT and full-term children aged 6–9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity (VPT, n = 28; full-term, n = 12). Multivariate analysis was used to explore potential biomarkers for socio-emotional difficulties in VPT children. Results The spatial organisation of the 13 retrieved functional networks was comparable across groups. Dynamic features and lateralisation of network brain activity were also comparable for all brain networks. Multivariate analysis unveiled group differences in associations between dynamical functional connectivity parameters with socio-emotional abilities. Conclusion In this exploratory study, the group differences observed might reflect reduced degrees of maturation of functional architecture in the VPT group in regard to socio-emotional abilities. Dynamic features of functional connectivity could represent relevant neuroimaging markers and inform on potential mechanisms through which preterm birth leads to neurodevelopmental and behavioural disorders. Impact Spatial organisation of the retrieved resting-state networks was comparable between school-aged very preterm and full-term children. Dynamic features and lateralisation of network brain activity were also comparable across groups. Multivariate pattern analysis revealed different patterns of association between dynamical functional connectivity parameters and socio-emotional abilities in the very preterm and full-term groups. Findings suggest a reduced degree of maturation of the functional architecture in the very preterm group in association with socio-emotional abilities.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

BackgroundMultiple facets of the pandemic can be a source of fear, depression, anxiety and can cause changes in sleep patterns. The aim of this study was to identify health profiles and the COVID-19 pandemic related factors associated with fear, depression, anxiety and changes in sleep pattern in adults in Nigeria.MethodsThe data for this analysis was extracted from a cross-sectional online survey that collected information about mental health and well-ness from a convenience sample of adults 18 years and above resident in Nigeria from July to December 2020. Study participants were asked to complete an anonymous, closed-ended online questionnaire that solicited information on sociodemographic profile, health profiles (high, moderate and low COVID-19 infection risk profile) including HIV status, COVID-19 status, and self-reported experiences of fear, anxiety, depression and changes in sleep patterns.ResultsIn total, 4,439 participants with mean age of 38.3 (±11.6) years responded to the survey. Factors associated with higher odds of having COVID-19 related fear were health risk (p < 0.05); living with HIV (AOR: 3.88; 95% CI: 3.22–4.69); having COVID-19 symptoms but not tested (AOR: 1.61; 95% CI: 1.30–1.99); having a friend who tested positive to COVID-19 (AOR: 1.28; 95% CI: 1.07–1.53) and knowing someone who died from COVID-19 (AOR: 1.43; 95% CI: 1.24–1.65). The odds of feeling anxious was significantly higher for those with moderate or low health risk profile (p < 0.05); living with HIV (AOR: 1.64; 95% CI: 1.32–2.04); had a friend who tested positive for COVID-19 (AOR: 1.35; 95% CI: 1.08–1.68) or knew someone who died from COVID-19 (AOR: 1.53; 95% CI: 1.28–1.84). The odds of feeling depressed was significantly higher for those with health risk profile (p < 0.05); living with HIV (AOR: 2.49; 95% CI: 1.89–3.28); and respondents who had COVID-19 symptoms but had not taken a test (AOR: 1.41; 95% CI: 1.02–1.94). Factors associated with higher odds of having sleep pattern changes were having moderate and low health risk profiles (p < 0.05).ConclusionThe study findings suggest that the pandemic may cause fear, anxiety, depression and changes in sleep patterns differently for people with different health profile, HIV status and COVID-19 status.

BACKGROUND: There is a notable comorbidity between externalizing disorders and anxiety disorders, which may be explained by the co-occurrence of two prevalent early-onset disorders, by shared vulnerability and risk factors, or as evidence that one disorder group might be causally related to the other.AIM: To investigate the longitudinal trajectories of externalizing disorders, their interplay with anxiety disorders, and putative predictors for symptom progression in youth.METHODS: 1053 adolescents (14-17 years) from the general population were assessed at baseline and prospectively at 2, 4, and 10-year follow-up using a standardized interview of mental disorders (DIA-X/M-CIDI) to assess "early" (oppositional-defiant disorder, conduct disorder, ADHD) and "late" (antisocial behavior, substance use disorders) externalizing disorders as well as anxiety disorders. Longitudinal associations and predictors for symptom progression were examined using Kaplan-Meier-analyses.RESULTS: Lifetime prevalence of early externalizing disorders were 9.1% and 6.4% among those with and without any anxiety disorder. A late externalizing disorder was reported by 50.3% of those with an early externalizing disorder and in 26.6% of those with any anxiety disorder. Both early (HR: 1.5, 95%CI: 1.0-2.3) and late externalizing disorders (HR: 2.1, 95%CI: 1.7-2.6) were associated with incident anxiety disorders. Higher parental rejection, lower volitional inhibition, and higher volitional avoidance predicted incident anxiety disorders among those with early externalizing disorders.DISCUSSION: Early externalizing disorders likely follow a homotypic continuity (to late externalizing disorders) and/or a heterotypic continuity to anxiety disorders, and thus appear as a useful target for prevention and early intervention.

Background: Our aim was to assess the occurrence and risk factors for psychotropic medication use after pediatric traumatic brain injury treated in the intensive care unit. Methods: We combined data from the Finnish Intensive Care Consortium database, data on reimbursed medications from the Social Insurance Institute, and individual electronic health care data. We analyzed data on children aged five to 17 years treated for traumatic brain injury in intensive care units of four university hospitals in Finland during 2003 to 2013 and being alive six months after injury with no history of psychotropic medication use before traumatic brain injury. Results: We identified 248 patients of whom 46 (19%) were prescribed a new psychotropic medication after traumatic brain injury. In multivariable logistic regression, a higher age associated with a higher probability for use of any psychotropic medication. Subgroup analyses showed that higher age associated with an increased risk of antidepressant and antipsychotic use but with a decreased risk of stimulant use. Apart from age, we found no other clinical, radiological, or treatment-related factors that significantly associated with subsequent use of psychotropics. Psychotropic medication was most common (45%) in children aged 12 to 17 years and had moderate disability at six-month follow-up. Conclusions: One fifth of children treated in the intensive care unit for traumatic brain injury were prescribed a new psychotropic medication during a median follow-up of three years and five months. Psychotropic medication was most common among teenagers with moderate post-traumatic disability. The need and use of psychotropics postinjury seem multifactorial and not related to any traumatic brain injury type. (C) 2020 Elsevier Inc. All rights reserved.

BackgroundThere is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.

The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.

A national study of clinical directors examined professional development (PD) focused on mental health provided to professionals in juvenile justice facilities for adjudicated youth. A total of 85 clinical directors responded to a mail survey (45% return rate). The survey questions related to (a) topics of staff training and the basis for choosing topics, (b) which professionals participated in each PD topic, (c) training format and frequency of PD, (d) recommended attributes of PD, (e) methods of evaluating PD, and (f) adequacy of PD and how can it be improved. For each topic, PD was typically provided once per year and face to face, rather than online. PD participation rates were commonly in the 30% and 40% ranges for professionals other than clinical directors and counselors, with teachers, correctional officers, administrators, and teaching assistants receiving PD the least. Rarely did PD include recommended attributes of PD, and it was commonly viewed as ineffective. Implications for research and practice related to PD and its relationship to youth reentry from juvenile justice facilities are discussed.

Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

Objective: Neurodevelopmental mechanisms are thought to play a role in the etiology of obsessive-compulsive disorder (OCD). Childhood traumas and neurological soft signs (NSSs) are more frequent in OCD patients. However, there has been no study that determined whether or not there is a relationship between childhood traumas and NSSs in OCD patients. The aim of this study was to determine the relationship between childhood traumas and NSSs in OCD patients and healthy individuals. Method: The study included 40 OCD patients and 40 healthy controls. Linear regression analyses were used to investigate the relationship between childhood traumas and NSSs which was evaluated with Neurological Evaluation Scale (NES) in OCD patients and the healthy control group. Results: The Childhood Trauma Questionnaire-28, Beck Depression Inventory, and Beck Anxiety Inventory scores were found to be higher in OCD patients. The NES total score, subscales of Şensory integration, complex motor sequences, and other NSSs were significantly higher in OCD patients. In the OCD group, age and emotional abuse were determined as variables predicting motor coordination, and age and physical neglect predicted both Şensory integration and complex motor sequences. In the healthy control group, age and emotional abuse were determined as variables predicting other NSSs, and physical neglect was Conclusion: This study demonstrated that childhood traumas may be related to neurodevelopmental impairment seen in OCD. The evaluation of NSSs could be another method to investigate the effects of childhood traumas on central nervous system development. The effects of childhood traumas should be considered in psychiatric disorders in which NSSs are severe.

Contains fulltext : 287469.pdf (Publisher’s version ) (Open Access) Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.