Autism and serotonin

Autistic Women Blog 2/7/2021 Originally posted on Spectrum

Serotonin’s link to autism, explained

Serotonin, the brain chemical best known for its link to depression, may also be involved in autism.

Serotonin has many roles throughout the body, including in mood, sleep, appetite and sociability. In the intestines, it stimulates muscles involved in digestion; in the blood, it causes vessels to shrink or expand; and in the brain, it relays messages between neurons. Its levels in the brain are closely tied to depression. Many antidepressants work by increasing the levels of serotonin at neuronal junctions.

Tenuous ties between serotonin and autism first surfaced decades ago. In 1961, a study of 23 autistic people reported that 6 of them had an unusually high level of serotonin in their blood. Since then, researchers have consistently found that about one in four people on the spectrum has high blood serotonin.

That result is “incredibly well replicated,” says Jeremy Veenstra-VanderWeele, professor of psychiatry at Columbia University.

Motivated in part by these results, several research teams have tested antidepressants as a treatment for autism over the past 20 years — with mixed results. Interest in serotonin’s role in autism has grown in the past five years, due in part to mouse studies that implicate the chemical in social behavior.

Here’s what we know so far about serotonin’s role in autism.

What could explain the high serotonin levels in the blood of people with autism?

Blood serotonin levels are controlled in part by a protein called the serotonin transporter, which moves serotonin from the gut, where most serotonin is made, into certain blood cells.

These levels are highly heritable, suggesting that genetic factors control them.

Some people with autism may carry variants in the serotonin transporter that enhance its ability to move serotonin into blood cells1. Mice with these variants have unusually high blood levels of serotonin and behaviors reminiscent of autism2.

What does serotonin do in the brain?

In the fetus, serotonin helps neurons form and travel to their correct locations; it also helps them link to other neurons at junctions called synapses3. Too much or too little serotonin can be harmful: Mice exposed to too much in utero show altered development in a brain region that responds to whisker movements4; those with too little have repetitive behaviors and social difficulties5.

In the mature brain, serotonin is a neurotransmitter: It relays messages between neurons. Its level at the synapse is tightly controlled by the serotonin transporter, which pumps serotonin back into neurons and recycles it for later use. This transporter may be altered in people with autism6.

What do blood levels of serotonin have to do with serotonin in the brain?

It is unclear, because serotonin in the blood cannot pass into the brain; the brain makes its own. Genetic variants that turbocharge the transport of serotonin into blood cells are predicted to have the same effect in neurons, effectively leaving less of it available to relay messages across synapses. Antidepressants might be able to help by restoring levels of serotonin at the synapse.

How does the brain’s serotonin level relate to autism?

Some studies point to low serotonin levels in the brains of autistic people.

When autistic adults adopt a diet low in the amino acid tryptophan — the raw material for serotonin — their repetitive behaviors worsen and their irritability increases7. They also show altered patterns of brain activity in regions involved in face processing, suggesting that serotonin influences social behavior8.

Brain-imaging studies also hint that some autistic children make too little serotonin in the brain, and in others, too little serotonin binds to its receptors9,10.

Can treatments that increase serotonin levels ease autism traits?

Possibly. Antidepressants that allow serotonin to remain at the synapse for longer seem to ease repetitive behaviors in some autistic adults11. These drugs, called selective serotonin reuptake inhibitors (SSRIs), have not yet been shown to benefit children with autism. But clinical trials of these drugs are hampered by powerful placebo effects that might make it hard to tease out the benefit.

Preliminary evidence suggests that in adults with autism, the active ingredient in the drug ‘ecstasy,’ which raises serotonin levels in the brain, seems to ease social anxiety.

Some mouse models of autism have low brain serotonin levels. Treating one such strain of mice with an SSRI starting at birth prevents autism-like social behaviors. And artificially boosting serotonin in in another mouse model makes the mice more social.

Do serotonin levels in utero affect a child’s autism risk?

Some studies have explored whether exposure to antidepressants in utero has any effect on autism risk. The answer is unclear. One problem is that researchers are often not able to separate the effect of the antidepressant from that of the mother’s underlying depression. Simply having a family history of depression, for example, is associated with autism.

Where is research on serotonin and autism headed?

Some researchers are testing whether drugs that activate serotonin receptors make mouse models of autism more sociable. Others are working on strategies that dampen the activity of the serotonin transporter without blocking it completely12.

References:
  1. Sutcliffe J.S. et al. Am. J. Hum. Genet. 77, 265-279 (2005) PubMed
  2. Veenstra-VanderWeele J. et al. Proc. Natl. Acad. Sci. USA 109, 5469-5474 (2012) PubMed
  3. Garbarino V.R. et al. Pharmacol. Res. 140, 85-99 (2019) PubMed
  4. Cases O. et al. Neuron 16, 297-307 (1996) PubMed
  5. Kane M.J. et al. PLOS One 7, e48975 (2012) PubMed
  6. Muller C.L. et al. Neuroscience 321, 24-41 (2016) PubMed
  7. McDougle C.J. et al. Arch. Gen. Psychiatry 53, 993-1000 (1996) PubMed
  8. Daly E. et al. Brain 137, 2600-2610 (2014) PubMed
  9. Chugani D.C. et al. Ann. Neurol. 45, 287-295 (1999) PubMed
  10. Oblak A. et al. Autism Res. 6, 571-583 (2013) PubMed
  11. Hollander E. et al. Am. J. Psychiatry 169, 292-299 (2012) PubMed
  12. Robson M.J. et al. Proc. Natl. Acad. Sci. USA 115, E10245-E10254 (2018) PubMed

Originally published on Spectrum

Spectrum logo

Great article by Spectrum

BY GEORGIA LOCKWOOD-ESTRIN  /  3 FEBRUARY 2021

Autism in girls: Jumping hurdles on the path to diagnosis

An autism diagnosis can affect people in many different ways. For some, it can be negative and put up additional barriers to education and employment. For others, however, it can be positive and open the doors to the support that they and their family need. It can also bolster someone’s sense of self and belonging within the autistic community.

Whether positive or negative — or, more likely, a mix of both — there is no denying that having a diagnosis makes the difference between accessing healthcare and support, or receiving nothing at all. But the journey to diagnosis is often lengthy, confusing and frustrating, which is problematic because early intervention is known to positively influence outcomes for autistic individuals and their families.

The barriers to diagnosis are especially challenging for women and girls. The research community is recognizing more and more that autistic women and girls are poorly served by the current clinical criteria and typical routes to a diagnosis.

What’s happening that leads to a later diagnosis, and delayed intervention and support, for girls compared with boys? My colleagues and I sought to investigate why in a review published in October in the Review Journal of Autism and Developmental Disorders. A big part of the problem, we found, is the ongoing perception that autism is a ‘male’ condition.

Layers of bias:

Historically, researchers, clinicians and other experts have not viewed autism as a female condition. From the first published descriptions of autism by Leo Kanner and Hans Asperger, most cases were described in boys and men.

Estimates of autism prevalence have found that boys are about four times as likely as girls to have a diagnosis, but the ways in which these estimates are calculated likely reflect biases in our perception, assessment and diagnosis of the condition. Prevalence estimates that reduce this bias put the sex ratio as low as 1.8 to 1.

Even before the diagnostic odyssey begins, boys are referred for an autism diagnosis 10 times as often as girls. And even with similar levels of trait severity, women and girls are less likely to be diagnosed than boys and men.

Women and girls with autism, even when they are referred, are diagnosed later than boys and men with the condition, studies show. This delay appears to exist despite there being no difference in how many visits they make to healthcare professionals, the age at which parents first express concern or the duration of their clinical assessments. They also experience greater stigma after they are diagnosed: For example, people are less likely to believe girls and women have autism than boys with the diagnosis.

My colleagues and I at Birkbeck College and King’s College London in the United Kingdom systematically searched the literature for results that might shed light on the potential barriers to an autism diagnosis for girls and young women. We found 13 quantitative, 6 qualitative and 1 mixed-methods paper meeting our inclusion criteria.

Shifting perspective:

Our analysis of these papers highlighted that in many cases, girls and women are diagnosed with autism only when certain traits, such as behavioral or language difficulties, are exaggerated, compared with boys and young men. This skew may be particularly problematic because girls and women, more often than boys and men, compensate for or mask aspects of their autism characteristics, according to many reports.

This masking is often referred to as ‘camouflaging.’ For example, autistic girls at school may intentionally or unconsciously hide their social communication difficulties in social situations, perhaps by mimicking the facial expressions of others. Camouflaging is a key reason why girls and women may not come to clinical attention and fail to reach diagnostic thresholds during assessments.

We found one overarching barrier that affects all levels of identification and diagnosis in girls and women: Autism is widely viewed as a ‘male’ condition.

Not only did parents initially face disbelief and skepticism from others when they expressed concerns about their daughters and the possibility of an autism diagnosis, but they were often met with mixed messages from clinicians and health professionals about the girls’ autism characteristics. In one paper we reviewed, a parent commented to one set of researchers, “I remember her [pediatrician] saying that this is usually a boys’ thing and she is only a little different.”

In some cases, parents said they felt like they had to exaggerate their daughter’s traits in order to obtain a diagnosis. “I felt that I needed to make my daughter look more impaired than she actually was, in order to get diagnosis and needed services,” one parent told another set of researchers.

Current male-centric ideas about autism are prevalent in our society and are detrimental to autistic girls and women and their families trying to get a diagnosis and much-needed support. To improve access to services for girls and women in a meaningful way, the general public’s, as well as clinicians’ and researchers’, perceptions of autism must change. There is a vital and urgent need for widespread recognition that autism occurs in both sexes and all genders. We need more research on autism in girls and women — and more effective dissemination of that knowledge to those in front-line positions, such as doctors, teachers and parents.

Georgia Lockwood-Estrin is a Sir Henry Wellcome postdoctoral research fellow at the Centre for Brain and Cognitive Development at Birkbeck College, University of London in the United Kingdom.

Originally published on Spectrum

Spectrum logo

“Weird” autistic habits

Autistic Women Blog 1/19/2021

I like this video. It discusses weird autistic traits as a child. I would add a few of my own “weird” traits. I chewed my nails until I was 21. I’ve only recently realized that I have an oral fixation. Another one would be living in a fantasy world in my head. I also get songs stuck in my head. Whatever the last song that I heard was (even commercials or really annoying songs) will by stuck in my head until I hear another one.

Autistic Burnout, “Regression,” and Identity Crisis – #TaketheMaskOff Week 4

I couldn’t have said it better myself!

Autistic Science Person

Part 1: Autistic Burnout – Playing on the Social Field

Autistic burnout = I literally can’t pretend and devote 90% of my energy to being on your social playing field anymore. Metaphorically, I have to go lie down in the grass because I’ve played too many games on the social field. No one will have noticed until I go and lie down, even though I was more exhausted than everyone else while playing the social games in the first place. But because I was still doing my best to keep up, and was able to keep up, even though it hurt, no one could notice my pain until I stopped playing the game.And that is dangerous for us. That means anxiety, depression, self-harm. That means that we don’t have any resources left to do daily tasks, or take care of ourselves, or to translate our thoughts to NT-speak. That…

View original post 1,049 more words

Autistic Masking, Late Diagnosis, and Dissociation: The Toll It Takes on Autistic Mental Health

It’s like you are reading my mind.

Autistic Science Person

CW: Gaslighting, self-harm, intrusive thoughts

(Long Post, Summary/Conclusion paragraph at the end)

This blog post came about after having a dissociation episode after watching Westworld a few nights ago. This post has helped me realize the reason and cause of my dissociation, likely from being an undiagnosed autistic person for 25 years of my life.

The Undiagnosed Autistic Life

Imagine all your life, you’ve been told that you just seem a “little” off. Just, you know, a little different. When you give your opinions, you’re either ignored, or simply told it’s “not a big deal” when you were not trying to complain, you were trying to collaborate. Whatever you do, whatever you say, is annoying, is rude, is unimportant, is inappropriate. Other people make excuses for you. “Oh you know, that’s just how she is. She’s just a bit different from the rest of us.”

GIF of the mother in Fantastic Mr. Fox talking to her son: "I know what it's like to feel, different." as she is wiggling her hands. GIF of the mother in…

View original post 1,877 more words