-
Cell & Bioscience Jun 2024Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions....
BACKGROUND
Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans.
RESULTS
In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137 miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137 miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD.
CONCLUSIONS
Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137 miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.
PubMed: 38937838
DOI: 10.1186/s13578-024-01268-8 -
BMC Psychiatry Jun 2024Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain.
METHODS
Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures.
RESULTS
We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08).
CONCLUSIONS
This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.
Topics: Humans; Mendelian Randomization Analysis; Autism Spectrum Disorder; Genetic Predisposition to Disease; Genome-Wide Association Study; Immunophenotyping; Inflammation
PubMed: 38937836
DOI: 10.1186/s12888-024-05927-5 -
Journal of Affective Disorders Jun 2024This short communication explores the interrelationships between depressed mood and sleep disturbances in one-year postpartum period.
BACKGROUND
This short communication explores the interrelationships between depressed mood and sleep disturbances in one-year postpartum period.
METHODS
Utilizing data from the Interaction of Gene and Environment of Depression during PostPartum Cohort (IGEDEPP) involving 3310 French postpartum women, we employed a cross-lagged panel model (CLPM) to analyze the relationships between these two symptoms, across three time points (immediate postpartum [<1 week after delivery], early postpartum [<2 months after delivery], and late postpartum [2 months to 1 years after delivery]).
RESULTS
Depressed mood significantly influences sleep disturbances in late postpartum (β = 0.096, z-value = 7.4; p < 0.001) but not in early postpartum (p-value = 0.9). We found no cross-lagged influence of sleep disturbances on depressed mood in early (p = 0.066) or in late postpartum (p = 0.060). Moreover, depressed mood and sleep disturbances in immediate postpartum are predictive of similar symptoms in the two other postpartum periods (between each of the three periods, p = 0.006 and p < 0.001 for depressed mood, and p = 0.039 and p < 0.001 for sleep disturbances), thus demonstrating the stability of these symptoms over time.
LIMITATIONS
Although conducted with a prospectively assessed cohort, this study faces limitations due to potential methodological biases.
CONCLUSIONS
This study is a pioneering analysis of mutual causal interactions between depressed mood and sleep disturbances in the postpartum period, highlighting the need for vigilant monitoring, early detection, prevention of worsen outcomes and intervention on these symptoms.
PubMed: 38936702
DOI: 10.1016/j.jad.2024.06.089 -
BJOG : An International Journal of... Jun 2024Over 70 000 donor-conceived (DC) people have been born in the UK since 1991. Little is known about their long-term psychological outcomes and no systematic review has... (Review)
Review
BACKGROUND
Over 70 000 donor-conceived (DC) people have been born in the UK since 1991. Little is known about their long-term psychological outcomes and no systematic review has assessed these.
OBJECTIVES
To conduct a systematic review of the psychological experiences of DC people through childhood and adulthood (Prospero: CRD42021257863).
SEARCH STRATEGY
Searches of Cumulative Index to Nursing and Allied Health Literature (CINHAL), the Excerpta Medica database (Embase), MEDLINE® and PsycINFO, conducted on 4 January 2024.
SELECTION CRITERIA
Quantitative and qualitative studies were included if: there were five or more participants; they were peer reviewed; and any DC psychological outcomes were assessed. No limits on date, language or country were applied.
DATA COLLECTION AND ANALYSIS
Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring.
MAIN RESULTS
Fifty studies (with 4666 DC participants), mostly from high-income anglophone countries, with heterogeneity of design, populations and outcome measures, were included. Of 19 comparative studies, 14 found no difference in outcomes between DC and non-DC people, ten found better outcomes (in health, well-being, self-esteem and emotional warmth) and six found worse outcomes (increased autism spectrum disorder and attention deficit hyperactivity disorder, addiction issues, mental illness, disruptive behaviour and identity problems). Qualitative data revealed common themes relating to identity formation, mistrust and concerns regarding genetic heritage. The evidence regarding adulthood outcomes was very limited.
CONCLUSIONS
The research on DC individuals presents a nuanced picture, with most studies suggesting comparable or improved outcomes in terms of well-being and relationships, but with a notable minority indicating higher rates of mental health and identity struggles. Qualitative findings underscore common negative experiences, whereas the early disclosure of DC status appears beneficial for psychological well-being.
PubMed: 38936405
DOI: 10.1111/1471-0528.17892 -
PloS One 2024The mental health of children conceived using Assisted Reproductive Technologies (ARTs) such as In-Vitro-Fertilization (IVF) is a subject of significant controversy....
BACKGROUND
The mental health of children conceived using Assisted Reproductive Technologies (ARTs) such as In-Vitro-Fertilization (IVF) is a subject of significant controversy. Existing studies suggest children conceived through ART meet physical and cognitive developmental milestones at similar rates to their spontaneously conceived peers, however, a significant number of studies have connected ART conception with mental health conditions, particularly depression and attention-deficit hyperactivity disorder (ADHD) in adolescence. This study, therefore, aimed to determine whether maternal use of ARTs to achieve pregnancy is associated with an increased risk of mental disorders in these children, and whether these effects are sex-dependent or confounded by known covariates in the ART population.
METHODS
Secondary data analysis was performed using Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) data; a nationally representative population-based cross-sequential cohort study. Multivariate logistic regression models examined the impact of ART (including IVF and other fertility drugs, from LSAC wave-1 and wave-2 conducted in 2004 and 2006, respectively) on mental health outcomes (i.e., autism, ADHD, anxiety and/or depression, from LSAC waves 8 conducted in 2018) in Australian adolescents aged 18-19 years in 2018 (n = 1735). Known sociological and obstetric covariates including maternal age, birth weight, smoking and drinking alcohol during pregnancy, maternal gestational diabetes, postnatal depression, hypertension, and socioeconomic status were considered to generate an adjusted logistic model. Variables with a p-value of <0.05 in the regression models were considered statistically significant.
RESULTS
Of the 1735 mother-child dyads analysed, the maternal mean age was 35.6 years (Standard deviation = ±4.75), approximately 5% of mothers (n = 89) used ART to become pregnant, and 22% of adolescents (n = 384) had a mental disorder. Longitudinal analysis revealed no relationship between ART and children developing a mental disorder in the LSAC population.
CONCLUSION
These results should reassure parents considering ART that there is no increased risk of psychological or neurodevelopmental problems in their ART conceived offspring.
Topics: Humans; Female; Adolescent; Longitudinal Studies; Australia; Reproductive Techniques, Assisted; Male; Mental Health; Young Adult; Pregnancy; Attention Deficit Disorder with Hyperactivity; Child; Adult; Depression
PubMed: 38935695
DOI: 10.1371/journal.pone.0304213 -
Revista de Neurologia Jul 2024The presence of psychiatric comorbidity in some neurological disorders is common. A bi-directional influence between some psychiatric and neurological disorders has been...
INTRODUCTION
The presence of psychiatric comorbidity in some neurological disorders is common. A bi-directional influence between some psychiatric and neurological disorders has been discussed, but not widely studied. There is an absence of literature on the typology and rates of neurology consultations in different types of psychiatric inpatients.
MATERIALS AND METHODS
Cross-sectional study based on real world data on patients who had a neurological consultation during hospitalization on a psychiatric ward.
RESULTS
The most frequent reasons for visits to neurologists in our study were cluster 'Epilepsy/other types of non-epileptic seizures' (n = 177, 36.44%), followed by cluster 'Movement disorders' (n = 77, 20.48%), 'Cognitive disorder' (n = 69, 18.35%), and finally cluster 'Neuropathy' (n = 21, 5.59%). The most frequent type of psychiatric patient who required neurologic consultation presented a psychotic disorder (n = 100, 26.60%), follow by problem behavior (n = 82, 21.81%), bipolar disorder (n = 78, 20.78%), depressive disorder (n = 42, 11.17%) and autism spectrum disorder (n = 20, 5.32%). We found a statistically significant relationship between (problem behavior and intellectual disability) and neurologic consultation for epilepsy/other types of non-epileptic seizures, and between (depressive disorder, bipolar disorder, autism spectrum disorder and intellectual disability) and neurologic consultation for movement disorders.
CONCLUSIONS
This is the first study in the literature which analyzes the rates and typology of neurologic consultations in people hospitalized with psychiatric disorders. A deep knowledge of epilepsy, movement disorders and cognitive disorders should be required for health professionals to treat psychiatric inpatients appropriately. Patients with particular psychiatric disorders seem to require a higher number of neurologic consultations than others during their hospitalization.
Topics: Humans; Cross-Sectional Studies; Female; Mental Disorders; Male; Spain; Nervous System Diseases; Middle Aged; Referral and Consultation; Adult; Comorbidity; Neurology; Inpatients; Aged; Epilepsy
PubMed: 38934945
DOI: 10.33588/rn.7901.2024054 -
The Behavioral and Brain Sciences Jun 2024Elizabeth Spelke's is a scholarly presentation of core knowledge theory and a masterful compendium of empirical evidence that supports it. Unfortunately, Spelke's...
Elizabeth Spelke's is a scholarly presentation of core knowledge theory and a masterful compendium of empirical evidence that supports it. Unfortunately, Spelke's principal theoretical assumption is that core knowledge is simply the innate product of cognitive evolution. As such, her theory fails to explicate the developmental mechanisms underlying the emergence of the cognitive systems on which that knowledge depends.
Topics: Humans; Infant; Child Development; Cognition; Knowledge
PubMed: 38934458
DOI: 10.1017/S0140525X23003102 -
Heliyon Jun 2024Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit.... (Review)
Review
Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.
PubMed: 38933955
DOI: 10.1016/j.heliyon.2024.e32251 -
Frontiers in Nutrition 2024Our core premise is that personalized variations of a ketogenic diet are likely to benefit pediatric patients with neuropsychiatric symptoms across multiple domains....
Our core premise is that personalized variations of a ketogenic diet are likely to benefit pediatric patients with neuropsychiatric symptoms across multiple domains. Although pediatric epilepsy is currently a well-accepted indication for a strict ketogenic diet, there is a dearth of knowledge and therefore clinical guidelines upon which to recommend nutritional ketosis for pervasive pediatric conditions such as autism spectrum disorder and ADHD, even when comorbid epilepsy is present. However, there are published cohort studies and current clinical trials implementing medical ketogenic therapies for cognitive impairment, psychiatric comorbidities, motor disability, and even neuroinflammation. As holistic practitioners, it is imperative that we consider the health of a child in its entirety - and additionally offer the ketogenic diet as a therapeutic option when it may be synergistic in treating extra-neurologic diseases such as obesity. While there are uniquely pediatric potential adverse side effects such as linear growth deceleration and micronutrient deficiencies, previous trials in epilepsy and our center's experience have already proven the ketogenic diet to be a low-risk intervention when optimized with appropriate patient monitoring and support.
PubMed: 38933892
DOI: 10.3389/fnut.2024.1408327 -
Frontiers in Psychology 2024Interoceptive awareness (IA) is crucial to understanding mental health. The Multidimensional Assessment of Interoceptive Awareness (MAIA) scale, available in... (Review)
Review
Interoceptive awareness (IA) is crucial to understanding mental health. The Multidimensional Assessment of Interoceptive Awareness (MAIA) scale, available in approximately 30 languages, has gained global recognition for its research applicability. This review highlights the critical importance of integrating IA evaluation in clinical settings, advocating for the MAIA scale's potential as a screening tool. Through an examination of academic databases, including Scopus, PubMed, Google Scholar, and J-STOR, our analysis spans seven mental health domains: eating disorders (ED), depression, stress, anxiety, autism spectrum disorder (ASD), chronic pain, and suicide ideation (SI). Thirty-eight studies showed links between several dimensions of IA with different disorders. That is, ED was related to Body Trust and Self-Regulation; anxiety to Body Listening, Emotional Awareness, and Self-Regulation; depression to Noticing and Emotional Awareness; ASD to Trusting, Emotional Awareness, and Noticing; chronic pain to Not-Worrying and Self-Regulation; and SI with Trusting. These insights hold profound implications for both clinical practice and mental health research. Integrating IA assessments into standard clinical protocols has the potential to improve our understanding of pathology, enrich patient care, and enhance therapeutic strategies.
PubMed: 38933585
DOI: 10.3389/fpsyg.2024.1244701