The Four Biological Subtypes of Autism

About this episode

In this episode, I'm taking you inside one of the most important and often overlooked pieces of the autism puzzle: your child's biology. When a child is diagnosed with autism, that diagnosis is based on behavior, and for most families, the story stops there. But underneath the same diagnosis, children can look completely different biologically, and once we begin supporting each child based on their actual biology, things start to shift in ways they couldn't before.

I walk you through the four broad biological categories researchers have identified, and the more specific subtypes within each. We start with metabolic, including how the mitochondria (the power plants inside every cell) produce energy, and the nutrient deficiencies like iron, vitamin D, B12, and folate that show up so often. Then we move to immune and inflammatory, where the brain's own immune cells, the microglia, are in constant conversation with the body. Next is cortical patterning, which is really about how the brain was physically built during pregnancy, and what a marker like head circumference can tell us. And finally single gene, where one identifiable gene shapes a recognizable pattern, in conditions like Fragile X, Rett, and tuberous sclerosis complex.

This episode is for you if: you've heard that there are "types" of autism but no one has explained what that actually means, your child struggles with sleep, digestion, energy, or sensory overwhelm and you're not sure why, you want to understand the biology behind your child's behavior, or you're looking for a science-backed framework that goes beyond behavior alone.

Transcript

Click a time to play the video from that point. This transcript comes from the episode’s captions and may contain small errors.

Welcome to Magnificent Minds, where we explore the science of child development with both heart and reason, bringing clarity, compassion and scientific evidence to questions that matter deeply to families. Did you know that there are different biological types of autism? Well, what does that mean? And what type is your child? That's what we'll answer today. When a child receives a diagnosis of autism, you'll almost never receive information about their biology. Because today, a diagnosis of autism is made based on behavior. And the truth is that for most children, it stops there.

They'll receive an autism diagnosis based on their behavior, like how they interact with others, how they play, how they communicate, and often they'll go on next to have further evaluation of their behavior. With an ABA assessment, they might have an evaluation also of their speech, language and communication with a speech language therapist. They might have an evaluation of their sensory and motor skills with an occupational therapist. All of these are important, but the fact is, most children today still do not get the right biological testing after an autism diagnosis. Many parents don't even know it exists.

And this is really important because when we do look at the biology underneath the diagnosis, what we find is that children with an autism diagnosis look completely different from each other. Same diagnosis, different biology underneath. And once we begin supporting each of them based on their actual biological profile, not just their behavioral profile, that's when things start to shift in ways that never could have before. After today's episode, you'll never think about autism the same way again. If you caught my recent episode on behavioral subtypes of autism. You know, we spent time looking at autism from the outside, the different ways autistic children behave, what their developmental and behavioral profiles look like, where their strengths are kind of support they need based on what we observe.

That episode was about what you see. This episode is about what's happening inside. There are a number of different and sometimes overlapping biological types of autism. Researchers use the word subtypes. Most children with autism diagnosis fit into one of them, and sometimes children fit into more than one. Most families don't know this. So I want to be clear about what biological subtyping actually is, because it's generating a lot of excitement in research right now, and also a lot of questions. What is it exactly? Well, here's the simplest way I can frame it.

Every autistic person has a unique nervous system, and that nervous system developed inside a body with its own particular biology, its own immune system, its own metabolism, its own genetic makeup, its own prenatal history. Biological subtyping is the science of understanding those underlying biological patterns so we can support each person more specifically, more accurately and more effectively. It's about saying, this child in front of me has a nervous system that works in a particular way, and I want to understand the full biological context that nervous system is living in, because that context shapes everything from their energy levels to their sensory experience to how they respond to support.

The science has advanced a lot recently, so let me walk you through each of the major biological subtypes. Researchers have identified. First, a warning, what most people, including most clinicians and even some researchers, get wrong about biological subtypes of autism is that they treat them like clean, separate categories with clear lines between them. But that's not how it works. These categories are not mutually exclusive. In fact, a child often has more than one at the same time because these subtypes are about biological characteristics and someone can have several.

So the biological landscape of autism is layered, and in many individuals, multiple patterns coexist and interact. Having one biological subtype does not mean you don't have the others. And I want to be honest with you about where the science actually stands right now. We don't yet have standardized, universally agreed upon criteria for identifying each of these subtypes with complete confidence. And different research groups are using different methods, and the boundaries between categories are sometimes genuinely blurry. The clinical tools to comprehensively characterize a child's full biological profile are still being developed and refined.

This doesn't mean the framework isn't useful. It absolutely is. These categories give clinicians and researchers a vocabulary, a set of questions to ask, and a direction to investigate. They help us look at a child and say what biological patterns might be contributing to their specific profile, and what can we do about them. But they don't replace the need to understand each autistic child as a whole, unique individual. We're still very much in the era of needing to understand each person's unique individual biology, and the biological subtype categories help us do that.

More precisely, they give us a biological map to guide us. If you're wondering whether your child's therapy program, their ABA, their speech language therapy, their occupational therapy, or in any other learning experiences, if you're wondering whether your child is progressing as much and as quickly as they should, you should not just be evaluating the quality of those services. You should also ask this question what's being done to support their biological health so they can get the most out of their therapy program? Because here is what I have learned across 25 years of working with autistic children.

Each child's autism is biologically unique, and a care team that isn't asking about their biological profile, about their health history, their energy patterns, their immune function, their genetics. Well, that care team is working with an incomplete picture. Behavioral and developmental support and biological understanding are not separate tracks. They belong together. A child whose cells are struggling to produce energy efficiently is going to find it harder to engage in therapy, no matter how skilled the therapist, no matter how hard the child is trying. A child with unaddressed inflammation that may have pain or other sensory experiences that make the environment genuinely overwhelming in ways that affect everything downstream.

Addressing the biology isn't instead of behavioral and developmental support, it's what allows that support to work as well as it possibly can. This is the foundation of everything I've built my career around, and this is what we do at Cortica. We bring together ABA developmental therapies, counseling and medical specialties, including neurology, so that we can actually look at the biology because autism care, done right, requires all of these lenses working together. We look at the whole child, we ask about biology.

We build care that is specific to this child, not a generic plan for autism in the abstract. So let me tell you about where we are today with understanding autism biological subtypes and the framework I use for broad biological categories, each containing more specific subtypes underneath. Those four broad biological categories are metabolic, immune, cortical patterning, and single gene. Now don't worry at all if these terms are new to you and you don't know what they mean.

I'll walk through each one. Let's start with metabolic. And the term metabolic refers to the biochemical processes in the body that convert nutrients into energy and clear out what the body doesn't need. Think of every cell as a tiny factory. Raw materials come in, energy gets produced. Waste gets hauled away. When part of that system isn't working and running smoothly, we can often see and measure where it's getting stuck. The most common subtype here is mitochondrial. Mitochondria are the power plants inside each cell.

And this is the aspect of autism that I spent many years researching when I was at Columbia University leading their autism clinic. In 2014, I published a research study with my colleagues at Columbia, where we used brain imaging to study mitochondrial function in autistic children and adults. What we looked for specifically in the brain is lactate, which is a marker of inefficient energy production. We found lactate at significantly higher rates in the brain and autism 13% versus 1% in non-autistic individuals.

Recent studies have found that about 5% of autistic children meet the full clinical criteria for what's called mitochondrial disease, and these are conditions where a gene mutation is the cause of mitochondrial deficiency. But a much larger group, potentially more than a quarter of autistic children, show meaningful biomarker evidence of a milder form of mitochondrial dysfunction that still affects how their cells produce energy. This broad biological category metabolic, which mitochondrial falls under, also includes different types of nutrient deficiency.

And research shows that 30 to 40% of autistic children have insufficient vitamin D or iron levels, regardless of their eating habits, and something like iron deficiency can show up as fatigue, paleness, or trouble with attention. Vitamin B12 deficiency is also more common in autism, and when vitamin B12 is low, it can cause developmental delays and learning difficulties. And another vitamin you might have heard of in relation to autism is vitamin B9, which is folate. Some autistic children have difficulty converting folate to its active form in the body, and some have low levels of folate in the brain.

Folate is necessary for brain development and helps cells to grow, repair, and function properly. This is when the medication leucovorin, which has gotten a lot of attention recently. This is when it can have an important role. When a child has a subtype of autism with disturbances of folate metabolism. Leucovorin is essentially a form of high dose folate. Also within the metabolic category are a set of metabolic disorders called inborn errors of metabolism, and these have a genetic cause and effect how the body processes different nutrients and gets rid of byproducts that need to be removed from the body.

These are found in roughly 3 to 7% of autistic children. So even though they're not extremely common, we have tests for them. It's important to identify them. If they're if they are present. And we have ways of treating many of them through dietary changes or targeted nutritional supplementation. Metabolism is a complex area, so understanding your child's metabolism and supporting them means having a doctor or nurse practitioner. So having a medical team who knows your child well and can make sure the right tests and treatments are done.

The second broad category is immune or inflammatory. And to understand this one, it helps to start with a simple fact. Your immune system and your brain are in constant conversation with each other. They are not separate systems. In fact, the brain actually has its own built in immune cells called microglia, whose job is to monitor the brain environment and respond to anything that seems like a potential threat. When the immune system is doing what it should, that conversation that runs in the background quietly and does a lot of important things.

But when the immune system is over activated or dysregulated, maybe sending out too many inflammatory signals or sending them at the wrong times, well, that can affect how the brain develops and functions. This can start even before birth. And we have good research now showing that significant immune activation during pregnancy, like from an infection or inflammatory illness that the mother experiences, well, this consent inflammatory signals across the placenta that affect how the fetal brain is developing. The brain is building itself at an extraordinary pace during pregnancy, and disruptions to that process during critical windows can have lasting effects on how the brain is organized.

And I want to be clear this is not about anything a mother did wrong. Infections and inflammation during pregnancy are common, and most mothers have no way of knowing that their immune system response is affecting fetal development. After birth, immune dysregulation can continue to show up in the brain itself, in the form of those microglia being chronically activated or ongoing low levels of neuroinflammation that affects how the brain is functioning and how the brain processes the world. For families, the subtype often looks like a child whose maybe sensory sensitivities are particularly intense, whose behavior or regulation seems to shift noticeably when they're sick, or who has recurring immune related health challenges alongside their autism profile.

The brain and the immune system are so interconnected that when one is dysregulated, you often see it in the other. A medical professional who understands the role of the immune system in autism will look for indications of immune differences or disorders in your child, and also in family members. Often these things run in the family, and they can make sure the right immune tests are done and they can guide you in appropriate therapies. The third category is cortical patterning. And this is one that is really about how the brain was physically built before your child was even born.

During pregnancy, the brain is under construction at a pace that's really almost impossible to comprehend. Billions of neurons are being born, traveling to their designated locations and organizing themselves into precise layers and regions. The outer layer of the brain, called the cortex, is where most of this complex organization is happening, and it's where a lot of our higher level thinking, sensory processing and communication happens throughout life. For some autistic children, something in that construction process unfolds differently.

Important research study published in the New England Journal of Medicine, looked at brain tissue from autistic children and found patches where the cortex wasn't organized into its normal layers, suggesting that during prenatal development, there was a disruption in how neurons were differentiating and finding their way to the right places. You can think of it like a city where some neighborhoods get built according to plan and others don't. The city still functions, but it functions differently and in ways that are specific to where the disruption happened. One of the most visible signs of this subtype can actually be something a pediatrician measures at every well child visit, which is head circumference.

Research has found that a subset of autistic children have a period of unusually rapid brain growth in the first years of life, resulting in a head size that's larger than typical. This isn't harmful in itself, but it is a marker, as something in their early brain building process was different and newer research is starting to uncover the specific biological mechanisms like excess neuron production, altered communication between cells, which is called cell signaling, and even the role of blood vessels in guiding where neurons travel during development.

These findings are more likely to show up when you look at images of the brain, like from an MRI scan, or you can get clues through a very detailed medical history, which is one reason it often goes unrecognized. Unless you're working with a doctor or other medical professional who knows to look for it. The fourth category is called single gene because there's often one single gene identifiable that's doing something differently. And that that particular gene is that change is significant enough that it produces a recognizable pattern.

Often that pattern has its own name. And so that recognizable pattern might include characteristics beyond autism itself. And all these different characteristics trace back to the same genetic change. Those other characteristics might include certain facial features or possibly disruptions to other body functions like the heart, the GI tract, the bones, hormones, or others. You may have heard of some of these like fragile X syndrome, rett syndrome, phelan-mcdermid syndrome, tuberous sclerosis complex sometimes called TSC, and another one called p-t-e-n or P10.

Related conditions. There are many others. Each of these involves a specific genetic variant that affects brain development in particular ways, and each comes with its own distinct profile in terms of what a child's development looks like, what medical monitoring might be helpful for them, and what support approaches are most relevant. What makes this category especially important right now is that it's one of the most actionable areas in autism. When you can point to a single gene, you can actually, in research studies, look exactly at what that gene does, why it matters, and increasingly, whether there are ways to address the biology specifically, there are already specific medical therapies for some of these conditions, and more research studies are underway.

My hope is that learning about these four biological categories, and all the biological subtypes within them, will help you better understand your child. Remember that having one identified subtype doesn't mean others aren't present. Often several are together. It's very common to have more than one. And in addition to these subtypes, it's also important to recognize other medical features that are part of a child's biological profile. Things like seizures, sleep disruptions, GI symptoms, ADHD, anxiety, allergies.

Because each of these is important and we can help with all of them, I feel very strongly every autistic child deserves to be understood in full, not just what we see on the surface, not just behavior, but the whole biological context. They're living in the unique pattern of their immune system, their energy metabolism, their genetics, their developing brain, all of it. Biological subtyping is giving us better tools to do that. The science is young and is evolving, and there's real humility required in how we apply it. But the direction is pointing toward toward more individualized, more biologically informed, more whole child care.

That direction is right. And if something in this episode made you wonder whether a deeper biological lens might add something to your child's care, I hope you'll explore it. At Cortica, it’s at the heart of everything we do. You can find more information about biological subtypes and about Cortica on our website at CorticaCare.com Thank you for joining me here on Magnificent Minds. I'll see you next time.