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Aaron Besterman

@abesterman.bsky.social
146 followers 204 following 62 posts

Child & Adolescent Psychiatry | Psychiatric Genetics| Neurodevelopmental Disorders | Precision Medicine

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Reposted by Aaron Besterman
Scott Myers @smyers20.bsky.social · 05/09/2026
Elevated Rates of Gastrointestinal Dysfunction in Children with Neurodevelopmental Disabilities: Not Just an Autism Issue | Sciety share.google/mZJzargL5d1F...
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Elevated Rates of Gastrointestinal Dysfunction in Children with Neurodevelopmental Disabilities: Not Just an Autism Issue
Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care ut...
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Reposted by Aaron Besterman
Yale Kavli Institute for Neuroscience @kavliatyale.bsky.social · 13/04/2026
In a new study, @yale.edu researchers led by @yaleschoolofmed.bsky.social's @ehoffmanlab.bsky.social, MD, PhD 🥼 identified a promising candidate to rescue disrupted brain activity in zebrafish carrying mutations in autism risk genes 🦓🐠
news.yale.edu
Zebrafish reveal new insights into the biology of autism
In a new study, Yale researchers identified drug candidates that reverse disrupted behaviors in zebrafish carrying mutations in autism risk genes.
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Aaron Besterman @abesterman.bsky.social · 07/04/2026
Idaho Cut Services for People With Schizophrenia. Then the Deaths Began. www.nytimes.com/2026/04/07/h...
nytimes.com
Idaho Cut Services for People With Schizophrenia. Then the Deaths Began.
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Reposted by Aaron Besterman
Boca Scientific Inc. @bocascientificinc.bsky.social · 10/03/2026
Researchers @sebatlab.bsky.social utilized long-read whole #genome sequencing and identified new #genetic variants associated with Autism. This enhanced the discovery of variants, leading to the potential for accurate testing and new therapies. #AutismSpectrumDisorder today.ucsd.edu/story/long-r...
today.ucsd.edu
Long-Read Genome Sequencing Uncovers New Autism Gene Variants
By utilizing long-read sequencing, an emerging technique that reads large sections of the genome at once, scientists at UC San Diego have revealed new genetic variants associated with autism spectrum ...
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Reposted by Aaron Besterman
UC San Diego Health Sciences @ucsdhealthsci.bsky.social · 09/03/2026
Out now in @CellGenomics: #LongRead sequencing reveals new genetic variants for #autism. Results could help yield new tests and treatments. #AutismResearch #AutismSpectrum @UCSDMedSchool.bsky.social @cp-cell.bsky.social buff.ly/PgUjYKZ
today.ucsd.edu
Long-Read Genome Sequencing Uncovers New Autism Gene Variants
By utilizing long-read sequencing, an emerging technique that reads large sections of the genome at once, scientists at UC San Diego have revealed new genetic variants associated with autism spectrum…
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Reposted by Aaron Besterman
Filipe De Vadder @filipedevadder.bsky.social · 19/11/2025
New Neuron paper by Mitchell, Dahly, Bishop tears apart the “autism is caused by the microbiome” story. Tiny n, noisy 16S, contradictory taxa, vague “dysbiosis”. It reads like an autopsy of a hype bubble. www.cell.com/neuron/fullt...
cell.com
Conceptual and methodological flaws undermine claims of a link between the gut microbiome and autism
Claims that the gut microbiome causally contributes to autism regularly appear in the scientific literature and popular press. Mitchell et al. critically examine influential studies underpinning these...
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Reposted by Aaron Besterman
Gregory Kohn @kohngregory.bsky.social · 24/01/2026
Great piece in the NYtimes with quotes from @stairwaytokevin.bsky.social and @sashagusevposts.bsky.social. The misuse of NIH datasets with sensitive personal information for racist aims should be concerning for anybody interested in scientific integrity. www.nytimes.com/2026/01/24/u...
nytimes.com
Genetic Data From Over 20,000 U.S. Children Misused for ‘Race Science’
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Reposted by Aaron Besterman
Nik Baya @nbaya.bsky.social · 06/01/2026
Why do some individuals defy their polygenic score? In the largest study of its kind (402k UKB individuals; 7 continuous traits + 3 diseases), we asked: If your phenotype deviates from common-variant polygenic score prediction, what's driving that difference? www.medrxiv.org/content/10.6...
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Reposted by Aaron Besterman
Alex Kwan @alexkwan.bsky.social · 15/12/2025
“Basic neuroscience hasn’t produced new drugs.” 💊 Not true - zuranolone (PPD), suzetrigine (pain), gepants (migraine), and more... were born out of a long arc of studies in the lab. I wrote a Perspective on why this matters. @thetransmitter.bsky.social www.thetransmitter.org/drug-develop...
thetransmitter.org
How basic neuroscience has paved the path to new drugs
A growing list of medications—such as zuranolone for postpartum depression, suzetrigine for pain, and the gepants class of migraine medicines—exist because of insights from basic research.
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Reposted by Aaron Besterman
Joe Pierre, MD @psychunseen.bsky.social · 22/11/2025
Pre-print of our case of new-onset AI-associated psychosis in a patient with no prior psychotic episodes. Although there have been many such reports in the media, I believe this the first case published in the academic literature. innovationscns.com/youre-not-cr...
innovationscns.com
“You're Not Crazy”: A Case of New-onset AI-associated Psychosis - Innovations in Clinical Neuroscience
Peer-reviewed evidence-based information in neuroscience research and practice, including psychiatry, neurology, psychology
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Aaron Besterman @abesterman.bsky.social · 10/12/2025
@erictopol.bsky.social @smotus.bsky.social @doctorveera.bsky.social @j9austin.bsky.social @jenforsyth.bsky.social @ispg.bsky.social @psychunseen.bsky.social @kingsioppn.bsky.social @wiringthebrain.bsky.social @quantpsychiatry.bsky.social @jacobvorstman.bsky.social
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Aaron Besterman @abesterman.bsky.social · 10/12/2025
Excited for our new study to come out that suggest that clinical genetic testing should perhaps be considered as part of the standard diagnostic evaluation for schizophrenia.
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Reposted by Aaron Besterman
Eric Topol @erictopol.bsky.social · 10/11/2025
No clear evidence to support any link between maternal acetaminophen (Tylenol) intake and autism or ADHD in offspring, a new umbrella, systematic review @bmj.com
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Reposted by Aaron Besterman
Jonathan Pritchard @jkpritch.bsky.social · 07/11/2025
Excited to share our latest work on the factors that determine what genes we find (and don't find!) in GWAS and burden tests. We describe a critical concept that we call *specificity*. Led by Jeff Spence and Hakhamanesh Mostafavi:
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Reposted by Aaron Besterman
The Transmitter @thetransmitter.bsky.social · 03/10/2025
The awarded projects plan to study gene-and-environment interactions in people, stem cells and organoids, as well as predictors of positive life outcomes in autistic youth and adults. By @callimcflurry.bsky.social www.thetransmitter.org/spectrum/mee...
thetransmitter.org
Meet the Autism Data Science Initiative grantees
The projects plan to study gene-and-environment interactions in people, stem cells and organoids, as well as predictors of positive life outcomes.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
@biologicalpsych.bsky.social @ispg.bsky.social
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
11/ Gratitude to an amazing collaborative team led by Harman Brah. @bogglerapture.bsky.social Pre-proof here: www.biologicalpsychiatryjournal.com/article/S000... #Schizophrenia #Genetics #Psychiatry #PrecisionMedicine #MetaAnalysis
biologicalpsychiatryjournal.com
Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis
Genetic testing may provide important diagnostic information for individuals with schizophrenia, but the frequency with which clinically significant variants are identified across different testing ap...
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
10/ For clinicians: consider genetics as part of a precision psychiatry approach—useful for prognosis, medical surveillance, reproductive counseling, and occasionally treatment considerations tied to specific variants (see our table of variants with clinical implications).
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
9/ What could improve yield over time: comprehensive reporting of both CNVs and SNVs, consistent ACMG/AMP interpretation, and attention to variant classes best captured by GS. As databases mature, VUS reclassification may further increase actionable returns.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
8/ Clinical take-home: These data do not constitute a practice guideline, but they can inform diagnostic workups—especially for schizophrenia with NDD features or early onset—and motivate services to build genetics pathways and counseling capacity.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
7/ Important caveats: substantial heterogeneity (I²≈96%), inconsistent CNV/SNV reporting across studies, and limited geographic representation (notably few data from Latin America, South Asia, Africa). The field needs better standardization and broader sampling.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
6/ Context: The Royal College of Psychiatrists has recommended considering CMA in schizophrenia. Our pooled estimate (~6%) is higher than earlier CNV-only figures, reinforcing that genetic testing can be clinically relevant—but standards and reporting practices matter.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
5/ Who benefits most (signal from meta-regression): higher yields in schizophrenia with co-occurring NDD features—especially intellectual disability—and earlier age of onset. These groups could be prioritized when considering clinical genetic testing.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
4/ Key result: ~6% pooled diagnostic yield (95% CI 4–7%). By platform: CMA ~6%, ES ~5%, GS ~7%. (Note: confidence intervals overlap; study methods & reporting varied.) This suggests ~1 in 17 patients may receive clinically informative findings.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
3/ What we did: Systematic review & random-effects meta-analysis across MEDLINE, EMBASE, and PsycINFO (2007–2023). We pooled platform-specific yields for chromosomal microarray (CMA), exome (ES), and genome sequencing (GS), and ran meta-regressions to probe heterogeneity.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
2/ Why this matters: genetic testing is now routine in many neurodevelopmental disorders (ID, ASD, epilepsy), yet adoption in schizophrenia has lagged—due to uncertainty about yield, variable reporting, and limited genetics training in psychiatry. We tackle that evidence gap.
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Aaron Besterman @abesterman.bsky.social · 03/10/2025
1/ 🚀 New paper out in @BiologicalPsyc1 “Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis.” We synthesize 31 studies to estimate how often clinical genetic testing returns positive results in schizophrenia. www.biologicalpsychiatryjournal.com/article/S000...
biologicalpsychiatryjournal.com
Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis
Genetic testing may provide important diagnostic information for individuals with schizophrenia, but the frequency with which clinically significant variants are identified across different testing ap...
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Reposted by Aaron Besterman
Emil Uffelmann @euffelmann.bsky.social · 27/09/2025
Our new paper is out, in which we developed an approach to transform Polygenic Scores (PGSs) into disorder probabilities (i.e., the absolute lifetime disorder risk). Below a thread 👇 open access link: rdcu.be/eIjvC
rdcu.be
Estimating disorder probability based on polygenic prediction using the BPC approach
Nature Communications - Here the authors present a method to transform polygenic scores into disorder probabilities using only GWAS summary statistics, genotype data and a prior - no tuning sample...
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
12/ SKS & PHTS families who participated Dr. Julian Martinez-Agosto (UCLA) @rarediseasectn.bsky.social @rarediseasesint.bsky.social @autismspeaks.org @simonsfoundation.org
dsc.rarediseasesnetwork.org
Home | Developmental Synaptopathies Consortium
Developmental Synaptopathies Consortium works to improve the lives of patients and families affected by developmental synaptopathies.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
11/🏁 Takeaway: Sensory profiles may provide a window into genetic pathogenicity across OGIDs, but variant scores alone aren’t robust prognostic tools. Individualized neurobehavioral assessment remains essential for diagnosis, prognosis, and intervention planning.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
10/🧩 Clinical classification: Decision tree using behavioral + medical features (e.g., neonatal teeth for PHTS) performed above chance (CV relative error ≈0.67). Behavioral-only tree also above chance, showing the strength of detailed phenotyping.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
9/Combined OGIDs (SKS + PTEN + PI3K–AKT–MTOR SFARI genes): • CADD ↗ SSP Low Energy & SSP Total • CADD ↘ SRS-2 Total T These were the most consistently stable correlations after 1,000 bootstrap resamples.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
8/ PTEN-specific: • CADD ↗ SSP Low Energy (r=0.72) • CADD ↘ SRS-2 Total T (r=−0.64) (both bootstrap-stable; p<0.05 uncorrected)
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
7/SKS-specific (missense only): • REVEL ↗ SSP Auditory Filtering (r=0.77) • AlphaMissense ↗ SSP Visual/Auditory Sensitivity (r=0.74) • REVEL ↘ DCDQ Control During Movement (r=−0.80) (all bootstrap-supported; p<0.05 uncorrected)
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
6/🧬 Pathogenicity scores overall: Cross-cohort correlations were limited/inconsistent. CADD showed the most stable associations—especially with sensory processing—supporting the need for deep phenotyping beyond variant scores alone.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
5/🔬 Protein-domain findings: PTEN phosphatase-domain variants → more severe social & executive deficits vs C2-domain variants. MTOR domain differences (FAT vs PI3K) not significant (sample-size limited in SKS).
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
4/Cohorts: SKS (MTOR) n=17, PHTS (PTEN) n=74, Macrocephaly-Autism n=33, Controls n=32. We profiled motor, adaptive, social, executive, sensory domains, ran domain-by-protein analyses, pathogenicity–phenotype correlations, and built diagnostic decision trees.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
3/Our central question: How much clinical and genotype–phenotype overlap exists across disorders in the same pathway? Given their rarity, can analyzing them together reveal new insights to improve diagnosis & care?
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
2/Smith-Kingsmore Syndrome (SKS) is caused by MTOR variants; PTEN Hamartoma Tumor Syndrome (PHTS) by PTEN variants. Both are overgrowth–intellectual disability syndromes (OGIDs) in the PI3K–AKT–MTOR pathway.
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Aaron Besterman @abesterman.bsky.social · 28/08/2025
1/ Thrilled to share our preprint: “Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype–Phenotype Relationships in the PI3K–AKT–MTOR Pathway.” 🔗 www.medrxiv.org/content/10.1...
medrxiv.org
Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype-Phenotype Relationships in the PI3K-AKT-MTOR Pathway
Overgrowth intellectual disability syndromes (OGIDs) caused by mutations in the PI3K-AKT-MTOR pathway present significant neurobehavioral challenges. While PTEN Hamartoma Tumor Syndrome (PHTS) has bee...
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Reposted by Aaron Besterman
Jonathan Sebat @sebatlab.bsky.social · 24/07/2025
We and @abesterman.bsky.social detected a TAN-DUP-DEL in a clinical case. Assembly of the complex SV was essential for determining the genetic diagnosis of RFX3 haploinsufficiency. It showed that the DEL occured within the FUNCTIONAL copy of the gene pubmed.ncbi.nlm.nih.gov/40200712/
pubmed.ncbi.nlm.nih.gov
Long-Read Genome Sequencing in Clinical Psychiatry: RFX3 Haploinsufficiency in a Hospitalized Adolescent With Autism, Intellectual Disability, and Behavioral Decompensation - PubMed
Long-Read Genome Sequencing in Clinical Psychiatry: RFX3 Haploinsufficiency in a Hospitalized Adolescent With Autism, Intellectual Disability, and Behavioral Decompensation
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Jonathan Sebat @sebatlab.bsky.social · 23/07/2025
Structural variants are significant contributor to autism. But many SVs & TRs are hard to detect with short reads. Long read sequencing with @pacbio.bsky.social and @nanoporetech.com captures and maps out alot of what short reads miss. So what can LR-WGS tell us about autism? 🧵
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Gerome Breen @psychgenomics.bsky.social · 17/06/2025
Excited about our new preprint: 1st successful genome-wide study of >61,000 panic attack and 29,000 panic disorder cases. www.medrxiv.org/content/10.1... We find 17 associations & evidence that peripheral neurons in eye, lungs and heart are involved in panic & other psychiatric disorders 1/n
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Nicky Whiffin @nickywhiffin.bsky.social · 11/04/2025
🚨I could not be more excited to share our new preprint on saturation genome editing of the small nuclear RNA (snRNA) RNU4-2: www.medrxiv.org/content/10.1... A super fun collaboration with incredible duo @gregfindlay.bsky.social @joachimdejonghe.bsky.social from @crick.ac.uk 🧬🖥️🩺 🧵1/12
medrxiv.org
Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
8/ Huge thanks to our patient & family, who generously agreed to share their story. Grateful to the incredible team across psychiatry, genetics, and genomics that made this possible. 🔗 Read the full paper here: psychiatryonline.org/doi/epdf/10.... @sebatlab.bsky.social
psychiatryonline.org
Psychiatry Online
PsychiatryOnline.org is the platform for all American Psychiatric Association Publishing journals, DSM, and bestselling textbooks, as well as APA Practice Guidelines, and continuing medical education.
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
7/ Key takeaway: 🧠 For psychiatrists treating neurodevelopmental disorders, genomic tools like LRS can transform diagnosis and care. But using them well requires multidisciplinary collaboration—and thoughtful communication.
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
6/ Genetic diagnoses like this do more than end the “diagnostic odyssey.” They open the door to: 🧠 Understanding biology 🧬 Family cascade testing 👨‍👩‍👧‍👦 Reproductive planning 🧪 Natural history studies 💊 And—someday—targeted therapies
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
5/ We also found something fascinating: The mother carried the rearrangement in mosaic form—not present in all her cells. This helped explain her lack of symptoms and clarified inheritance for family counseling.
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
4/ This rearrangement resulted in RFX3 haploinsufficiency—a loss of function consistent with the patient’s behavioral and developmental profile. A diagnosis that could not have been made with short-read WGS alone.
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Aaron Besterman @abesterman.bsky.social · 09/04/2025
3/ 🧬 Enter long-read sequencing (LRS): Unlike short reads (~150bp), LRS captures sequences 10,000–20,000bp long—ideal for detecting complex rearrangements. In this case, LRS uncovered: 🔁 A duplication 🧱 An insertion ✂️ A deletion …all disrupting RFX3.
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