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Apr 11 • 9 tweets • 6 min read
Are some diseases products of traits that are intrinsically vulnerable to failure? The deadline this Friday for #ISEMPH2022 abstracts inspires a deep dive into #schizophrenia genetics. @isemph @HumBehEvoSoc @BioengineerGM @rcpsych
isemph.org
In this week's Nature, Singh et al. report 10 ultra-rare variants that substantially increase the risk of schizophrenia, some more than 50 fold. Remarkable progress. Huge studies with deep sequencing are paying off! @RiadhAbed1 @ent3c @AllenFrancesMD
nature.com/articles/s4158…
In another landmark study published simultaneously, Trubetskoy, et al. report fine-mapping 287 common genomic loci each with small effects, but together accounting for substantial schizophrenia risk.
nature.com/articles/s4158…
However, high genetic correlations between depression and GAD, and between schizophrenia and bipolar disorder, mean that these are not discrete disorders with specific simple causes. Now what?
The polygenic risk score deciles for schizophrenia from 4 studies are fascinating...3x more risk at the high vs low scores. But many individuals with schizophrenia are in low-risk deciles. Are their diseases caused by ultra-rare variants or common ones? We need to find out.
Despite their high genetic correlation, schizophrenia and bipolar disease PRS patterns are very different, as are the prevalences of alleles associated with high or low cognitive performance. SO much of interest here. @IBG_CUBoulder @TriCEM_NC @BernieCrespi
Work by many is needed to figure out what this means. But I hope to make a case at #ISEMPH2022 for how strong selection created by the wrenching transition to the social-cognitive niche acting on massively pleiotropic traits left some traits intrinsically vulnerable to failure.
Finally, a research idea: test hypotheses about possible benefits of disease-associated variants by studying individuals in the LOWEST polygenic risk deciles. If they have deficits, that would be very important. But I bet they are just fine or better. nesse.us
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More from @RandyNesse

Randy Nesse Profile picture
Apr 4
My virtual Grand Rounds Wed at 1 pm ET at @McGovernMed U Texas Psychiatry will be open access at uthealth.webex.com/uthealth/j.php…
It is so hard to choose the insights from evolutionary biology that will be valued most by clinicians and researchers. Here are candidates. Which are best?
Anxiety and low mood are adaptations shaped by natural selection, but individual instances are usually useless, even when regulation mechanisms are normal. Understanding why is crucial for clinicians and researchers, and helpful for patients. @ISREorg @WellcomeLeap @DrHowardLiu
A Review of S.O.C.I.A.L. Systems identifies life problems otherwise never found and helps to determine if associated emotions are useful.
-Social status, friends, and groups
-Occupation
-Children and family
-Income and possessions
-Abilities, appearance, and health
-Love and sex
Read 10 tweets
Randy Nesse Profile picture
Apr 2
The best example of kin selection? Multicellular bodies. Their cells are all identical twins whose interests are perfectly aligned, thanks to meiosis producing gametes with only one copy of a genome, and somatic cells sequestered from the germ line. For mitochondria, however...
multiple copies are transmitted in female gametes. The resulting genetic competition creates what David Haig cogently describes as a "tragedy of the cytoplasmic commons."
He describes brilliantly how the potentially dire consequences of that competition have shaped mechanisms to control mutations that benefit mitochondrial genes at the expense of cells and their hosts.
dash.harvard.edu/bitstream/hand…
Read 8 tweets
Randy Nesse Profile picture
Feb 12
On #DarwinDay it is wonderful to anticipate the fast progress coming to psychiatry as it discovers its missing foundation in evolutionary biology.
@isemph @HumBehEvoSoc @AllenFrancesMD @mentaldaily_com @Got_Anxiety @sse_evolution @eshb @RiadhAbed1 @PFinuras @APAPsychiatric
The day between #DarwinDay and #ValentinesDay gives an opportunity to respond to questions about
what #evolution offers to #psychiatry and
why I think it will bring fast progress.
Painful emotions, especially anxiety & depression, are by far the most common reasons people seek help. An evolutionary perspective recognizes emotions as special states shaped by natural selection along with control systems that express them in situations where they are useful.
Read 18 tweets
Randy Nesse Profile picture
Jan 19, 2021
#Antidepressants seem effective in the clinic but not in controlled studies. Why? Let’s consider all possibilities. @PeterDKramer @AllenFrancesMD @DrHowardLiu @DalackMd @blackdoginst @NAMICommunicate @Got_Anxiety @EikoFried @PsychTimes @matthewckeller @RiadhAbed1 @APAPsychiatric
Most of us who have prescribed antidepressants for thousands of patients have heard hundreds of them report transformed lives. “It is as if I walked out of a dark room into sunlight” “All of a sudden I can experience pleasure again”
But perhaps the effectiveness is an illusion. The improvement of patients taking #placebo is barely better than that for those taking antidepressants.
Here are 10 reasons why antidepressants
->Could seem effective when they are not, or
->Could seem ineffective when they are
Read 18 tweets
Randy Nesse Profile picture
May 20, 2020
The flood of articles offering “Quick tips for controlling your Covid anxiety” makes me nervous. After 30 years treating patients in one of the first specialty clinics devoted to anxiety disorders, I should have super advice, right? Not really, but here are 6 observations. Image
Quick tips can help but they can be worse than useless. Exercise, eat right, get sleep, talk with friends, and challenge negative thoughts. Like diet suggestions, they can help, but they can be hard to follow, ineffective, or prone to make some people feel like failures.
Some articles advise readers they MUST control their anxiety to avoid heart disease and cancer. There is hardly any evidence that anxiety directly causes medical illness but worry about that can initiate a vicious cycle that turns ordinary anxiety into a serious problem. Image
Read 8 tweets
Randy Nesse Profile picture
May 31, 2019
Starting June 1, I will tweet a chapter each day from my new book goodreasons.info about how the light of evolutionary biology can dissolve the mists that swirl around mental disorders. Well, some mists for some disorders. @DuttonBooks @hbes2019 @LondonEvolution @ISEMPH
From the Preface: I wanted to write this book as soon as I realized that evolution could explain why bodies are vulnerable to disease. But the rest of medicine had to come first. Why We Get Sick stirred lots of interest. The new book is about why mental illness exists at all.
For each chapter I address the question, "So what?" Saying what is true changes only views unless it also changes what people do. Mental health clinicians who understand evolution do their work differently and better. For all others, self-understanding is valuable in itself.
Read 87 tweets

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