Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Янв. 21, 2023

The excitatory/inhibitory (E/I) imbalance hypothesis posits that between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I arises it may differ across autism symptomatology brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set gene-expression profiles in relation to cortical thickness (CT) investigate relationships genetic variance, structure participants from AIMS-2-TRIALS LEAP cohort (autism = 359, male/female 258/101; neurotypical control 279, 178/101) aged 6-30 years. Using analyses, we investigated whether aggregated variation glutamate GABA gene-sets could be associated with measures symptoms structural variation. Further, using same gene-sets, corelated expression throughout cortex differences CT autistic participants, as separate sensory subgroups. was all symptom severity scores on Autism Diagnostic Observation Schedule-2 (ADOS-2) Interview-Revised (ADI-R) within group. In adolescents adults, greater genes showed although opposing directions. Additionally, gene were Our results suggest complex related genetics alterations, where there differential roles for GABA.

Язык: Английский

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Novel treatments in autism spectrum disorder

Current Opinion in Psychiatry, Год журнала: 2022, Номер 35(2), С. 101 - 110

Опубликована: Янв. 18, 2022

Purpose of review There are currently no approved medications for the core symptoms autism spectrum disorder (ASD), and only limited data on management co-occurring mental health behavioural symptoms. The purpose this is to synthesize recent trials novel treatments in ASD, with a focus research trends past 2 years. Recent findings No new pharmacologic agents received regulatory approval use ASD. Several large randomized controlled (RCTs) had negative or ambiguous results (e.g. fluoxetine, oxytocin). A cross-over RCT an oral cannabinoid suggested possible benefits disruptive behaviours. Two large-scale multicentre bumetanide were terminated early lack efficacy. Multicenter using repetitive transcranial magnetic stimulation underway. meta-analyses indicate that specific psychological interventions can support social communication treat anxiety. Numerous treatment targets informed by biological mechanisms under investigation. Summary anxiety ASD; more regarding pharmacotherapy associated Next steps include replication findings, molecular targets, identification biomarkers, including genetic predictors, response.

Язык: Английский

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Hidden impacts of ocean warming and acidification on biological responses of marine animals revealed through meta-analysis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 3, 2024

Conflicting results remain on the impacts of climate change marine organisms, hindering our capacity to predict future state ecosystems. To account for species-specific responses and ambiguous relation most metrics fitness, we develop a meta-analytical approach based deviation from reference values (absolute change) complement meta-analyses directional (relative) changes in responses. Using this approach, evaluate fish invertebrates warming acidification. We find that drivers induce calcification, survival, metabolism, significant deviations twice as many biological responses, including physiology, reproduction, behavior, development. Widespread are detected even under moderate intensity levels acidification, while mostly limited more severe levels. Because such may result ecological shifts impacting ecosystem structures processes, suggest will likely have stronger than those previously predicted alone.

Язык: Английский

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Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Март 4, 2024

Abstract Background Autism spectrum disorder (ASD) and attention-deficit/hyperactivity (ADHD) are neurodevelopmental disorders with overlapping behavioral features genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD ADHD separately, the degree to which associated common distinct patterns of CTh changes is unclear. Methods We searched PubMed, Web Science, Embase, Science Direct from inception 8 December 2023 included studies comparing youth (age less than 18) or typically developing controls (TDC). conducted a comparative meta-analysis vertex-based identify ADHD. Results Twelve datasets involving 458 individuals 10 383 were analysis. Compared TDC, showed increased bilateral superior frontal gyrus, left middle temporal right parietal lobule (SPL) decreased temporoparietal junction (TPJ). precentral gyri, postcentral TPJ relative TDC. Conjunction analysis both shared reduced located default mode network (DMN). Comparative analyses indicated had greater SPL dorsal attention thinner ventral Conclusions These results suggest DMN an neurobiological feature This alteration together might be related altered biological motion processing ASD, while abnormalities sensorimotor systems may contribute control problems The disorder-specific disparate networks provides novel insight into symptoms attentional deficits two disorders. Trial registration PROSPERO CRD42022370620. Registered on November 9, 2022.

Язык: Английский

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Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

Biological Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Autism and attention-deficit/hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation sex-biased prevalence, autism ADHD rarely studied together sex differences often overlooked. Population modeling, referred to as normative provides a unified framework for studying age-specific sex-specific divergences in brain development.

Язык: Английский

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Sex differences in trajectories of cortical development in autistic children from 2–13 years of age

Molecular Psychiatry, Год журнала: 2024, Номер 29(11), С. 3440 - 3451

Опубликована: Май 16, 2024

Abstract Previous studies have reported alterations in cortical thickness autism. However, few included enough autistic females to determine if there are sex specific differences structure This longitudinal study aimed investigate and trajectory of thinning across childhood. Participants 290 (88 females) 139 nonautistic (60 individuals assessed at up 4 timepoints spanning ~2–13 years age (918 total MRI timepoints). Estimates early late childhood as well the were modeled using spatiotemporal linear mixed effects models age-by-sex-by-diagnosis. Additionally, spatial correspondence between maps sex-by-diagnosis neurotypical evaluated. Relative their peers, had more extensive than males. These involved multiple functional networks, mainly characterized by thicker cortex ~3 faster females. Cortical regions which different sexes significantly overlapped with that differed development. Autistic males demonstrated some shared rate relative however these areas relatively small compared widespread observed sexes. results support evidence sex-specific neurobiology autism suggest processes regulate differentiation brain contribute etiology

Язык: Английский

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Cortical Thickness Differences in Autistic Children With and Without Intellectual Disability

Autism Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Of the 1 in 36 individuals United States who are diagnosed with autism spectrum disorder, nearly 40% also have intellectual disability (ID). The cortex has been widely implicated neural processes underlying autistic behaviors as well ability. Thus, neuroimaging features such cortical thickness of particular interest a possible biomarkers condition. However, studies often fail to include ID. As result, there few across entire range abilities. This study used MRI evaluate young children (n = 88, mean age 5.37 years) large ability (IQ 19-133) nonautistic, nondevelopmentally delayed (referred here typically developing [TD]) peers 53, 5.29 years). We first investigated associations between full scale IQ and both TD children. Autistic had significant negative (i.e., thinner cortex, higher IQ) bilateral entorhinal right fusiform gyrus, superior, middle inferior temporal gyri, pole that were not present Significantly thicker was observed these regions for ID ≤ 70) compared those without. Last, given reported correspondence severity symptoms ability, we ADOS Calibrated Severity Scores found patterns overlapped degree cortex.

Язык: Английский

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Neurobiological Correlates of Change in Adaptive Behavior in Autism

American Journal of Psychiatry, Год журнала: 2022, Номер 179(5), С. 336 - 349

Опубликована: Март 25, 2022

Objective: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that associated with significant difficulties in adaptive behavior and variation clinical outcomes across the life span. Some individuals ASD improve, whereas others may not change significantly, or regress. Hence, development of “personalized medicine” approaches essential. However, this requires an understanding biological processes underpinning differences outcome, at both individual subgroup levels, lifespan. Methods: The authors conducted longitudinal follow-up study 483 (204 279 neurotypical individuals, ages 6–30 years), assessment time points separated by ∼12–24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale–II), neuroanatomical (structural MRI), genetic (DNA). Individuals were grouped into clinically meaningful “increasers,” “no-changers,” “decreasers” behavior. First, compared neuroanatomy between outcome groups. Next, they examined whether deviations from profile level. Finally, explored observed differences’ potential underpinnings. Results: Outcome groups differed features (cortical volume thickness, surface area), including “social brain” regions previously implicated ASD. Also, predicted Moreover, relevant to phenotypes (e.g., synaptic development). Conclusions: This demonstrates, for first time, (adaptive) group- individual-level anatomy brain enriched genes facilitate move toward better targeted/precision medicine approaches.

Язык: Английский

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The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression

American Journal of Psychiatry, Год журнала: 2022, Номер 180(1), С. 50 - 64

Опубликована: Ноя. 23, 2022

The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. authors sought to elucidate relationship between and typical sex-differential neuroanatomy, cognition, related gene expression.Using a novel deep learning framework trained predict biological based on T1-weighted structural brain images, compared prediction model performance neurotypical autistic males females. Multiple large-scale data sets comprising MRI were employed at four stages analysis pipeline: 1) pretraining, with UK Biobank sample (>10,000 individuals); 2) transfer validation, ABIDE (1,412 individuals, 5-56 years age); 3) test discovery, EU-AIMS/AIMS-2-TRIALS LEAP set (681 6-30 4) specificity, NeuroIMAGE ADHD200 (887 7-26 age).Across both LEAP, features positively predictive average significantly more (ABIDE: Cohen's d=0.48; LEAP: d=1.34). Features females less d=1.25; d=1.29). These differences accuracy not observed individuals ADHD. In females, male-shifted neurophenotype was further associated poorer social sensitivity emotional face processing while also expression patterns midgestational cell types.The results demonstrate an increased resemblance female individuals' neuroanatomy male-characteristic typically cognitive patterns. findings hold promise for future research aimed refining quest mechanisms underpinning etiology autism.

Язык: Английский

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Immunogenetics of autism spectrum disorder: A systematic literature review

Brain Behavior and Immunity, Год журнала: 2023, Номер 114, С. 488 - 499

Опубликована: Сен. 16, 2023

The aetiology of autism spectrum disorder (ASD) is complex and, partly, accounted by genetic factors. Nonetheless, the underpinnings ASD are poorly defined. presence immune dysregulations in autistic individuals, and their families, supports a role system its regulators. Albeit responses belong either to innate or adaptive arms, overall genetics broad, encompasses multitude functionally heterogenous pathways which may have different influences on ASD. Hence, gain insights immunogenetic ASD, we conducted systematic literature review previous transcription studies We defined list genes relevant explored neuro-immune function. Our confirms variability inherited variations expression changes blood post-mortem brain individuals. Besides function, identified control neurodevelopment processes (neuronal synaptic plasticity) highly expressed pre/peri-natal periods. our synthesis bolsters hypothesis that perturbation contribute derailing typical trajectory neurodevelopment. also helped identifying some limitations prior research Thus, alongside clarifying genes, outline key considerations for future work into possible novel intervention targets.

Язык: Английский

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