PCOS and the Brain: Neurodivergence
PCOS is first and foremost a disorder of the full body. Anyone who tells you PCOS is only a fertility or weight issue is discrediting a great deal of what PCOS can impact. Research has shown that PCOS may be caused by a combined dysfunction of the nervous and endocrine systems. Several studies have found that fluctuating hormones can be one of the key influencing factors in defects in cognitive function. Sex hormones act as membrane receptors, activating certain communication and signaling between our cells, and can alter cellular function. The PCOS impact on the hypothalamus-pituitary gonadal (HPG) axis, which is responsible for our reproductive function, makes it difficult for our entire bodies (including the brain!) to properly interpret and produce hormones like progesterone, luteinizing hormone, and follicle-stimulating hormone. This can prime our bodies to function inefficiently or in a way that may not have been intended, influencing neurotransmitters, metabolism, brain function and more. Enter: the association between PCOS and neurodivergence.
What is neurodivergence?
Neurodivergence, or sometimes referred to as neurodiversity, is a non-medical umbrella term for a group of conditions that may cause the brain to function in a way that’s not viewed as “neurotypical”. Many conditions fall into this category, including autism spectrum disorder (ASD), attention deficit-hyperactivity disorder (ADHD), bipolar disorder, dyslexia, dyscalculia, and obsessive compulsive disorder (OCD). Neurodiversity or neurodivergence is a word that allows us to define these conditions in a nonnegative way for what they are: a unique way of functioning in and viewing the world. Similar to PCOS, the emergence of neurodivergent conditions are thought to be caused by a combination of both genetic and environmental factors. It has also been suggested that exposure to higher levels of androgens in utero (meaning if your biological mother had elevated androgens during pregnancy) there is a higher chance of developing conditions like ASD or ADHD. Now, how is our brain functioning in a unique way related to PCOS? Let’s dive in.
pcos and neural network programming: hormonal imbalances
Hormones are chemical messengers in our bodies. They function to inform our cells how to operate and are involved in many feedback loops, including the suppression or production of certain hormones, and even the way different regions of the brain communicate with each other.
pcos and Relative Estrogen Dominance
PCOS is commonly associated with relative estrogen dominance, meaning that absolute levels of estrogen may be high in relation to levels of progesterone. The imbalance can cause a host of symptoms, but let’s stay focused on the brain. Estrogen and progesterone stimulate neuron growth, as well as a process called synaptogenesis and dendritic branching, which are heavily involved in the way our neural pathways are formed. Effectively, these are the habits we develop and the way we come to know the world. Neurite outgrowth is essential for wiring our nervous system in utero, during early development, and when certain life events may call for a rewiring. This rewiring may look like changing habits and neural pathways, or the way our brain functions on autopilot, when faced with a certain event. Events may include trauma, illness, exposure to toxins, and many other environmental factors. Dendritic branching is critical for the way our neurons function, as well as connecting various regions of the brain. Now, if some of the key hormones that play a role in helping us form neural pathways are out of balance, those neural pathways may develop in utero, or during life, in a way that isn’t seen as the “norm”.
Various regions of the brain have estrogen receptors including the hippocampus, the amygdala and the cerebral cortex. These regions of the brain are needed for emotional regulation, memory consolidation and retrieval, and general cognitive function. When too high, estrogen can lead to altered cognition, emotions, and various other neural factors. However, it is worth noting that this is about balance. Estrogen has also been shown to serve as a “neuro protector”, meaning that when in proper levels, it has selective benefits with cognitive tasks, like forming memories.
pcos and insulin resistance
It is estimated that up to 80% of those with PCOS have insulin resistance, meaning our bodies do not respond properly to insulin, leading to an overproduction of insulin. If left untreated, insulin resistance can lead to high levels of blood sugar and potentially prediabetes/diabetes.
One study showed that with PCOS and insulin resistance, there was a correlation between elevated plasma insulin levels and decreased levels of brain activity in the left middle frontal gyrus. This is a region of the brain used for working memory, attention and language processing. A similar correlation was found between elevated insulin and decreased brain activity in the left posterior cingulate gyrus. This part of the brain is used to help us recall specific events, and to help hone our focus if we are surrounded by distractions. It’s also associated with regulation of negative emotions like anxiety and fear, and processing of positive emotions. This can lead to trouble recalling events and difficulty staying focused. It may also lead to trouble focusing if we cannot regulate negative emotions like anxiety and fear.
Another study showed that high levels of insulin and/or insulin resistance in PCOS is associated with a lower utilization of glucose, or energy, in the brain. The regions of the brain impacted are those associated with attention, decision-making, planning, working memory, language processing, memory and object recognition.
Outside of PCOS, numerous studies have shown that high levels of insulin in the blood after fasting, which is highly correlated with insulin resistance, is associated with verbal fluency challenges, memory and attention issues. It can also disrupt the balance of neurotransmitters necessary for mood and behavior, and imbalances of neurotransmitters are often implicated in neurodivergence.
pcos and high levels of stress
If we were exposed to high levels of stress during childhood/adolescence, our HPA axis may have been impacted, leading to a production of excess glucocorticoids. When glucocorticoid levels are too high or too low, it can impact the functionality of our brain, as well as the way it develops. When glucocorticoid levels fluctuate often, or dramatically, the hippocampus is particularly vulnerable. We can then experience hippocampal atrophy, which alters the neural pathways in our brains responsible for functions like consolidation and recall of memories.
chronic low-grade inflammation
When inflammation is chronic, which is common in PCOS, cytokines or immune cells are released. These cytokines can travel to the brain via the blood/brain barrier, and data show significant effects on the metabolism of neurotransmitters like serotonin, dopamine and glutamate. Cytokines also function to deplete tryptophan, the precursor for serotonin. Dopamine and serotonin are both used for cognitive functions like working memory and learning, behavior modification, motivation to work and learn, and more. Glutamate is involved in synaptic plasticity, or the ability of the brain to modify and adapt to new information.
By disrupting these neurotransmitters, cytokines can significantly impair motor activity and motivation, anxiety, arousal and alarm systems. And, as we touched on during the insulin resistance section, many neurodivergent conditions are associated with an imbalance in neurotransmitters.
high oxidative stress
Oxidative stress is also highly associated with both insulin resistance and inflammation. Inflammatory cues from the body communicate to the immune system that there is a pathogen it needs to ward off. The immune system produces reactive oxygen species, leading to an attack on neurotransmitters. Interestingly, many recent studies have found a link between ASD and elevated oxidative stress. ASD may be caused by oxidative stress through protein post-translational changes, abnormal metabolism, and toxic buildup of reactive oxygen species.
common neurodivergent conditions and their symptoms
autism spectrum disorder (Asd)
ASD is a term used to define a broad range of conditions that may be characterized by difficulty communicating, difficulty socializing, narrow interests or hyperfixations and/or repetitive behaviors
ASD Associations with PCOS: Note, more research is needed
Those with ASD have a two-fold increase in manifesting PCOS
Those with PCOS have a 35% greater chance of having a firstborn child with ASD
asd Common symptoms
Sensory overload
Difficulty understanding what others are thinking/feeling
Difficulty and severe anxiety with social situations
Anxiety over a change in routine
Discomfort with eye contact
Hyperfixations on niche topics
Difficulty keeping up with learning pace of peers
Difficulty with emotional regulation
Sensitivity to textures, whether with food, clothes, etc.
Talking over others
Intense pattern recognition
Note: often symptoms of ASD can overlap with ADHD. See below
Attention Deficit Hyperactivity Disorder (ADHD)
ADHD is a neurodivergent condition characterized by pervasive attention deficit or hyperactivity. It may present as inattentive, hyperactive-impulsive, or a combination of the two.
adhd associations with pcos
If a mother has PCOS and elevated androgen levels, the developing fetus can be at a higher risk for ADHD, influenced through dendritic morphology, nerve density, abnormal synapse function, and morphology. Gestational diabetes, obesity, and preeclampsia have all been associated with both PCOS in the mother and a higher likelihood of ADHD in the child.
common symptoms of adhd in females
Frequent daydreaming
Anxiety or depression
Picking at skin, cuticles, hair
Perfectionism
Difficulty with details
Procrastination and executive dysfunction
Easily distracted
Excessive talking
Rejection sensitivity dysphoria
Racing thoughts
Difficulty with organization
Trouble keeping or making friends
Trouble following directions
Careless mistakes
Frequently losing thing
Cycles of intense productivity followed by action paralysis or burnout
bipolar disorder
Bipolar disorder is characterized by extreme mood swings with emotional highs like mania or hypomania and extreme lows of depression. Bipolar I is characterized by at least one manic episode preceded or followed by manic or major depressive episodes. Bipolar II is characterized by a minimum of one major depressive episode and one hypomanic episode, without a manic episode.
BPD and PCOS
A study out of the Taiwan National Health Insurance Research Database found that those with PCOS compared to healthy controls had an increased risk of developing bipolar disorder. Interestingly, those treated for insulin resistance with metformin reduced their risk of developing BPD.
COMMON BPD SYMPTOMS
RANGING FROM ONE END OF THE SPECTRUM…
Abnormal upbeatness
Increased activity or energy
Euphoric state
Very talkative
Racing thoughts
Impulsivity
Decreased need for sleep
…to the other
Depression, sadness, emptiness, hopelessness
Loss of pleasure in most activities
Intense weight fluctuations
Insomnia or sleeping constantly
Restless, or slowed behavior
Fatigue
Unexplained feelings of worthlessness and guilt
Suicidal thoughts or plans
obsessive compulsive disorder (Ocd)
Obsessive compulsive disorder is characterized by unwanted, intrusive thoughts, images or urges that produce anxiety and distress. Someone with OCD may develop certain patterns of behavior to help them mitigate feelings of distress
ASSOCIATION OF PCOS AND OCD
More research in the space is needed, but studies have suggested that genetically predicted PCOS increased the risk of developing OCD, and there is higher incidence of OCD in the PCOS population vs. those without PCOS
Symptoms of OCD
Obsessive thoughts
Patterns of behavior to mitigate distress
Taboo thoughts about violence, sex, religion, etc.
Fear of being contaminated by germs
Aggressive thoughts about yourself or others
Excessive cleaning or handwashing
Needing things to have a certain order or place
Repeat checking of things causing distress, like a locked door or powered down appliance
Compulsive counting
DYSLEXIA AND DYSCALCULIA
Dyslexia and dyscalculia are learning disabilities that make reading and math, respectively, difficult
SYMPTOMS OF DYSLEXIA
Struggles with reading
Difficulty sounding out words
Difficulty memorizing
Working memory issues
Avoids reading aloud
Suboptimal spelling or grammar
Difficulty comprehending what’s read
Confuses order of letters
SYMPTOMS OF DYSCALCULIA
Difficulty learning to count
Struggles with basic computation
Trouble recalling math facts
Difficulty understanding math concepts
Trouble interpreting graphs and charts
Working memory troubles
If you are suspicious you may have a neurodivergent condition in addition to your PCOS, know you are not alone! Scheduling time with your general practitioner, or psychiatrist if you have one, can help you determine next steps. They may use the DSM-5 to help you hone in on a particular condition.