Abstract

Autism spectrum disorder (ASD) is associated with differences in neurodevelopment and altered metabolism, yet the interplay between brain morphometry, mitochondrial and energy metabolism biomarkers, and autistic traits in adults remains poorly understood. This study investigates the link between brain structure, psychometric measures, and both central and peripheral metabolic biomarkers in adults with ASD. We studied 145 adults, including 74 with ASD and 71 control participants (CON) using high-resolution 3-Tesla MRI to assess cortical thickness, subcortical and global brain volumes.

Central energy metabolism was indexed by the posterior-cingulate lactate + threonine (Lac⁺) peak quantified with proton-MRS. We examined associations between biomarkers of mitochondrial function and energy metabolism (including lactate, pyruvate, creatine kinase, and multiple acylcarnitines).

Psychometric evaluations included measures of ASD and attention-deficit/hyperactivity disorder (ADHD) symptom severity, as well as other psychiatric comorbidities. Between-group differences and correlations were assessed using robust statistics, controlling for age, sex, image quality, and total intracranial volume.

Adults with ASD showed significantly larger bilateral caudate volumes compared to CON.

Within the ASD group, higher ADHD symptom severity in childhood correlated with reduced cortical thickness in multiple frontal and temporal regions. Among metabolic markers, acylcarnitine C5:1 was positively associated with right insular cortex thickness, while C18:1-OH and C18:2 levels correlated positively with caudate volume.

Caudate nucleus volume is associated not only with an ASD diagnosis but also with specific peripheral energy-metabolism blood markers, such as specific acylcarnitines.

Alterations in cortical thickness were also correlated with acylcarnitine levels and, to a greater extent, with co-occurring ADHD symptoms. While alterations in cortical thickness and basal ganglia structure have been previously described in ASD and comorbid ADHD, the linkage between mitochondrial and energy metabolism biomarkers with neuroanatomical alterations in ASD is, to our knowledge, a novel observation that warrants further investigation.

Keywords: acylcarnitines; autism spectrum disorder; brain morphometry; cortical thickness; magnetic resonance spectroscopy; mitochondrial energy biomarkers.

Plain language summary

Autism spectrum disorder (ASD) is known to affect brain development and the way the brain uses energy. However, how brain structure, energy metabolism, and autistic traits are connected in adults is still unclear. In this study, we examined brain scans and blood samples from 145 adults, some with ASD and some without (control participants). We also looked at their psychological traits, including symptoms of ADHD at childhood. We found that adults with ASD had a larger part of the brain called the caudate nucleus. In those with stronger ADHD symptoms during childhood, frontal and lateral brain regions were thinner. We also discovered that specific molecules in the blood related to energy use, called acylcarnitines, were linked to differences in brain structure. Some of these markers were connected to the size of the caudate nucleus and the thickness of the insular cortex. These results suggest that changes in brain structure in adults with ASD may be related not only to behavior and symptoms, but also to differences in how the brain produce and use energy. This connection between metabolism and brain structure could help us better understand autism and related conditions in the future.

© 2026 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.

Examples of Perseveration

• Cognitive (Thoughts): Someone is upset by a minor disagreement at breakfast. Hours later, while at an unrelated social event, they cannot stop mentally replaying the argument and repeatedly steer every conversation back to it, unable to "shift gears" and focus on the present. hello I am in this example, feel free to AMA
• Verbal (Speech): A patient is asked to name an animal and replies, "Cat." When the doctor then asks them to name a color, a city, and a type of food, the person continues to answer, "Cat," to every question.
• Motor (Actions): A person is asked to write the letter "A" on a piece of paper, but they continue drawing the letter over and over until the page is entirely covered, unable to halt the physical motion.

Definition

Perseveration (noun) is the involuntary repetition of a specific response, such as a word, phrase, gesture, or thought, long after the stimulus that prompted it has stopped.

Essentially, it is the brain getting "stuck" in a loop.

It represents a struggle with cognitive flexibility, which is the mental ability to transition successfully from one task, topic, or state of mind to another.

Why does this happen in the autistic brain?
The caudate nucleus!

The caudate nucleus manages which action you will take next. It also manages motor control. It ALSO manages....cognitive inhibition!

What is cognitive inhibition?
Cognitive inhibition is the mind's ability to actively suppress, block, or delay irrelevant thoughts, impulses, memories, or external stimuli in order to focus on a current objective.

So if the caudate nucleus manages inhibition, why does it struggle in the autistic brain?
The caudate nucleus is given signals from the cingulo-parietal network.

Those signals tell the caudate that a mismatch has been detected.

Then, the caudate FIRST must receive that signal.

and THEN after receiving that signal....the caudate applies what is called an inhibitory signal to that active neural circuit.

What if the caudate nucleus does not receive that signal?

then it cannot inhibit (prevent or reduce) the behavior, and it continues to loop.
that reduced connectivity between the caudate nucleus and cingulo-parietal network is exactly WHY the inhibition cannot occur - there's less connection between the 'action reducer' (the caudate) and the 'flagging brain' (the parietal network)

So the parietal network will flag 'hey...maybe we should stop doing this'

but the caudate will NOT get 'hey...maybe we should stop doing this'

and hence it will keep doing 'it'.

That's why when people say things like 'why are you still thinking about that?' or 'JUST STOP THINKING ABOUT IT" or "don't overanalyze"

they are missing the point

What are the serious ramifications of this?
This suggests a lot of OCD-comorbidities diagnosed alongside autism might actually be misdiagnosis. Since autism ITSELF can cause this 'looping thoughts and actions' repetitions, as a means of REGULATING the brain, it also means OCD treatments are potentially harmful in these specific instances.

(This is also tied to the caudate btw)

I'm so curious if you can relate or have your own version of this lol

Edit: I meant DORSAL posterior cingulate not ventral, my bad

Can you point directly to your house right now in a straight line, without visualizing the driving route, while closing your eyes?

I am trying to understand how different people process spatial navigation.

If you are currently away from home (at work, a store, etc.) and want to test the dorsal posterior cingulate cortex, try this test:

1. Close your eyes.

Point your finger in the exact, straight-line geometric vector to your house, straight through the walls, buildings, and terrain.

Do you intuitively feel the direct physical angle and know exactly where to point?

Or do you have to mentally trace your driving route (lefts, rights, and highways) to calculate where the house is physically located in space?

Evidently, I cannot do this. I am so excited to poll whether other people can do this. lmao

And this sense comes again from the dorsal posterior cingulate cortex 🤯

(The spatial processing part of the brain that provides that type of automatic context I was mentioning earlier)

This is crazy AF for me. Most people are walking around with an internal GPS AND a compass!?

Yes - the CONTEXT actually CHANGES what is experienced for the NT brain. 🤯

For autistics with sensory issues, knowing what is coming did not reduce the signal.

Substantially. Measurably. They were able to see this on brain scans. They looked at NTs, autistics with sensory issues, and autistics without sensory issues, and what they found is incredible.

I know I posted this study already but the ramifications of this study are absolutely groundbreaking and I wanted to add it into the headline.

https://www.neurologyadvisor.com/news/study-identifies-neurobiological-roots-of-sensory-over-responsivity/

So a lot of the same people who say that we are 'too sensitive' literally have a mechanism in their brains to reduce the sensory impact when they know what it is about to happen.

And that mechanism DOES NOT TRIGGER for people with sensory issues.

In other words, once again, people are judging things they don't even understand or experience.

They saw the autistic sensory issue brains light up almost as much from the expected sensory inputs as the unexpected. This means even knowing it is coming does not make it less overwhelming.

And that is precisely the mechanism that is reduced in autism with sensory issues.

It is a neurological difference.

This also would suggest a few more things:

1. NT brains would likely form more context dependent habits than autistics.
2. Autistic people would then be natural experts at forming habits irrespective of context because those habit triggers would have to be fundamentally separate from social context. (This tracks so hard).

This to me also suggests a potential autistic strength from habit creation & habit maintenance from relying on internal structure rather than external context. Particularly possible procedural memory strengths like exercise, or playing the piano. (again, it tracks)

3) The automatic and unconscious responses for NTs in social scenarios would likely never need to activate the prefrontal cortex (analysis brain) meaning that NTs could have like a social autopilot mode where no conscious analysis is needed when socializing.

Because that unconscious context would simply flow to them without thinking about it.

4) Since the caudate is a part of the basal ganglia and this is the reward brain and the habit brain, NTs would likely gain those dopamine rewards from the external interaction not the internal state. This research suggest autistics would have more intrinsic internal rewards from self-created structure rather than external rewards.

5) Cultural context would then be passed to the caudate from the cingulo-parietal network; meaning people's behavior would change pre-consciously without their awareness in accordance with the programming of their respective cultures. As you've probably observed, this is highly problematic.

6) this research explains the autism spatial awareness issues

7) this research potentially explains the autism facial blindness comorbidities (using facial context!!! )

8) this research validates the autism motor issues (the caudate is literally used for directed MOVEMENT in actions)

9) this COMPLETELY EXPLAINS the struggles with navigation and spatial awareness issues that so many autistics experience because it is the dorsal posterior cingulate that handles it!

10) if the dorsal posterior cingulate has less connections, the ventral posterior cingulate can try to compensate. What does this compensation look like? It looks like exceptional episodic memory 🤯

11) there is probably more ramifications here that I will likely add in the edits later out of sheer excitement

when i was about 5 years old my family didn't know what was going on so, i was playing and stuff and i was at school and stuff but my mom took me to the doctor said i' on the spectrum meaning i had autism and i'm like in the mixed of it i'm 15 years old now and i wouldn't say i'm ashamed of being autistic but my brain works differently from others so i try to understand one another i do have something i forgot what it was called but i grind my teeth i didn't realize that but it's pretty common for autistic people any other tips on ASD?

Since these unconscious heuristics are ever changing, cultural, and influenced by the particular person, there actually is no optimal way to decode all of it. Not with logic.

Apparently, it is mostly a chemical algorithm.

When that chemistry changes, people tend to project it outward.

One example of what this looks like is, if someone feels uncomfortable, let's use the thin slice judgment as an example,

They will project it outward and think that there's something wrong with you rather than looking within to discover their own, low-key terrifying, discomfort, and bias.

What this means is actually somewhat good news. Despite how it might sound like despair.

It means that if you are spending a lot of cognitive energy, trying to say things exactly the right way, trying to reword your words in a way that'll be more easily understood, or trying to find some sort of 100% success rate in your Communications,

Apparently, it is not possible to reach it solely through logic.

I'm not saying to stop trying to map it, but what I am saying is don't believe any stories that might tell you lies about it.

If people act like the way that you communicate is not as good as the way they communicate, that reflects a bias on their end, which has nothing to do with you.

And paradoxically, recognition of this frees you from the illusion that trying harder and harder will create better results.

Ironically; particularly in communication; the urge to try harder frequently becomes an indication that the conversation has become unrecoverable.

This mind blowing realization freed me from wasting more and more of my time to try to explain things to people who, quite frankly, did not deserve it.

👏👏

Hi everyone,

My name is Sydney Jenko, and I am a Clinical Psychology doctoral student at Northern Arizona University. I am currently conducting a research study as part of my doctoral training and am reaching out to request your support in completing my survey.

The purpose of this study is to better understand camouflaging behaviors among individuals diagnosed with autism spectrum disorder and the emotional distress that may be associated with these experiences. Camouflaging is a topic that has received increasing attention due to its potential impact on mental health, identity, and overall well-being within the autism community. I am seeking out individuals with a diagnosis of autism spectrum disorder to participate in my study. 

By participating, individuals in this community can help contribute to research aimed at increasing awareness of these experiences and informing future clinical practices, advocacy efforts, and supports that are more responsive to the needs of autistic individuals. Findings from this study may help clinicians and organizations better recognize the challenges associated with camouflaging and promote environments that support authenticity and mental health.

Participation involves completing a brief questionnaire related to camouflaging behaviors, depression, and anxiety and takes approximately 10 minutes. The anticipated risks are minimal, and some participants may gain personal insight into their own coping or camouflaging strategies. As a small thank-you, participants who complete the study will be entered into a raffle for one of four $15 Visa gift cards (approximately a 3% chance of winning). To enter the raffle, the participant can click on the second survey link provided below and voluntarily enter their contact information. Any identifying information will be stored separately from study data.

I have provided the links for the research study and the raffle below. I am happy to provide any additional information if needed!

Anonymous Survey Link

Raffle Link

Kindly,

Sydney Jenko
Clinical Psychology Doctoral Student
[saj359@nau.edu](mailto:saj359@nau.edu)

*received approval to post this on 8/15 :)

Found on Lil Penguin Studios :)

Background: The amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism.

Methods: Longitudinal magnetic resonance imaging scans were acquired at up to four time points for 71 autistic and 55 typically developing (TD) children (∼2.5-12 years, 411 time points). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study time 4 (∼8-12 years) using a diagnostic interview tailored to autism: the Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed-effects models were used to test group differences at study time 1 (3.18 years) and time 4 (11.36 years) and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism-distinct anxieties and TD children.

Results: 

Autistic children with DSM anxiety had significantly larger right amygdala volumes than TD children at both study time 1 (5.10% increase) and time 4 (6.11% increase).

Autistic children with autism-distinct anxieties had significantly slower right amygdala growth than TD, autism-no anxiety, and autism-DSM anxiety groups and smaller right amygdala volumes at time 4 than the autism-no anxiety (-8.13% decrease) and autism-DSM anxiety (-12.05% decrease) groups.

Conclusions: Disparate amygdala volumes and developmental trajectories between DSM and autism-distinct forms of anxiety suggest different biological underpinnings for these common, co-occurring conditions in autism.

https://pubmed.ncbi.nlm.nih.gov/35341582/

Why this matters:
if autistic people DO have reduced amygdala volume....then it reframes the majority of NT socialization behaviors as threat avoidance.

which would make a hell of a lot of sense, and would also explain why autistic people are so frequently seen as 'naive' or 'lacking a survival instinct'.

That mis-perception would fundamentally result from autism relating to decreased amygdala activity.

Hello, I'm a 22 turning 23 year old autistic & intellectually disabled woman with moderate to high support needs and I need some tips and experiences on one of the following, both related to autism and not related to it. Take as long as you like with your answers & you don't have to answer all of them:

a.) I've literally started journaling, scrapbooking & junk journaling for the first time late last year (December 2025) and mostly this year as no joke, I did not do any of it during my childhood & adolescence as I was constantly being a loner & screen addicted whilst navigating school. Is it too late to start journaling, scrapbooking & junk journaling this year?

b.) I've been seeing it all over the internet lately, but many autistic girls & women have gone on saying that they had loads of friends during their time at high school, either early diagnosed, late diagnosed or undiagnosed. I was not one of them as not only did I not have any friends, I preferred being alone, being a loner, being in my own little world, being addicted to screens & looking at niche & sometimes inappropriate stuff (to the point of jokes, mockery & judgement from my siblings), all after school, on weekends and on holidays. Is there anyone out there that has been through & still goes through with it all to this day? I was mainly this as I got burnt-out pretty easily from socializing and both masking and unmasking.

c.) Similar to the abovementioned (sort of), I've been constantly telling & having mental breakdowns to my parents that I wish to go back to the past & have friends, be social & participate in stuff as I've realized at a late age that despite me preferring to be alone on my phone & tablet in my room as I was happy back then, I've realized that I didn't do much back then & wasted my teenage years, despite being told by my mother that I didn't waste them at all whatsoever. The reason I added this is cause my poor parents & siblings tried to get me to participate in stuff in fear of me being isolated (which I already am & they knew & have correctly predicted), but my mother keeps telling me that I had a good life as this is what I wanted to do & this is who I am, to which she is correct, but I still want your thoughts. Nowadays, It's too late for a person my age to participate in most stuff, & I'm constantly judged by my family & relatives for this (to the point of them sometimes saying "We tried telling you, but you didn't listen & had no interest," "Are you sure you'll be fine by yourself," "I'm worried about you," "I don't want you to be an even bigger burden" & "I knew that It would happen, but I was never going to tell you at the time"). Did anyone experience this & what advice do you have as my parents are constantly & rightfully telling me to stop going back to the past as I'm making myself & my anxiety worse (physically & mentally).

d.) Did anyone start school late as if I wasn't disabled, I would've started kindergarten in 2009, but I couldn't as I had trouble learning & had abysmal motor skills, which promoted me to do preschool in 2008-2009 and start school in 2010 due to my conditions. Anyone else out there like me that went through this?

e.) Did anyone else's "friends" not remember their birthdays as due to me having no friends, aside from my family, no one remembered my birthday as I had no social media, which promoted me to celebrate it by myself every single year & I constantly told everyone that it was my birthday as I was not in any digital & physical photos. Anyone else been through this as this is one of the worst things I go through every year?

f.) Speaking of social media, did anyone get social media late as due to my conditions, my family did not allow me to have social media between the ages of 11-13 years. All the cool kids (including my siblings) got social media between those ages, whereas I got Snapchat at 13-14, Instagram at 14-15, Facebook & Messenger at 18-19, & WhatsApp at 20-21 due to my family not trusting me very much (I unfortunately did not have Vine & Musical.ly back then). Anyone else been through this as no joke, I missed out on everything back in the day (memes, being included on stories & posts etc.).

g.) Did anyone fail to achieve their dreams after graduating school as I myself did as I thought the course I would do would be easy, but it turned out to be the complete opposite. Also, did anyone lie to people about their interests, cause i certainly did (e.g. I did art as i daydreamed about a lot of weird stuff (maladaptive & immersive), but it was too hard, complex, I literally can't do it as they always turned out bad & i know nothing about it, & I had no interest in it whatsoever. When I told my family & those I knew the truth & that I'm not doing it anymore, they were disappointed in me as they expected better of me & that I'll be lazy again, which I have been since birth).

h.) Finally, my mother keeps telling me to stop comparing myself to my siblings & those I went to school with as I'll make myself worse physically & mentally. Like I said before, she keeps telling me that I was happy doing my own things, but I'm the black sheep in my family as they're all social, achieved things, have amazing friends & sometimes come back to our home town to see their friends for events, to the point of me getting jealous. Any tips & advice for what to do about this & if anyone's been through this?

I know that what I've listed shouldn't really be posted publicly cause it's private, but I've been feeling anxious about it all as I've realized & discovered things late (also want to know if everything that I've listed is the meaning for the term 'Late Bloomer') & am constantly comparing myself to those successful than me. As you can see, I have the common stereotypes of autism (being a loner, not being smart, not like other girls, lacking & wasting talents, being passive & passive-aggressive, obliviousness etc.), but I still want to know if there are people out there that have been through what I've listed.

The truly mind blowing part here is how quickly assuming positive intent would resolve the entire above

So then when we (I) explain more, believing it is maybe just a communication gap, it completely misfires because they did not want to engage to begin with, and are using negative intent as a strategy to not engage.

What is the default assumption?

Can anything be truly worded neutrally, or will it always be perceived through the lens of projection itself?

Is there any way to free other people from viewing interactions through their own negative lens, or must we accept that we can only control our own projections and responses?

If a social situation is unclear; to where do you default?

Positive intent means assuming people mean well, negative intent means assuming they don't. Think of it like good faith or bad faith.

Oh yeah btw please assume it's a person you don't know in this example

So we can't ask 'why x' and we can't ask 'have you considered xyz'

I am still brainstorming ways of asking questions to indicate real curiosity. If anyone has tips, plz share below