Brain Health, ADHD, Depression & Cognition: The Role of Inflammation, Stress & the Gut–Brain Axis

The brain is an organ, just like the heart, the lungs or the liver. When the brain is not functioning properly, symptoms may include poor concentration, depression, anxiety, memory problems, or what many people describe as “brain fog.” We are going to be talking about the actual health of the organ, and in doing so, many seemingly unrelated symptoms may improve. Do not think of this as treatment—anxiety and depression, for example, may have causes that go beyond brain physiology.

Inflammation

Inflammation affects all organs, including the brain. In fact, it can be argued that because of its lipid content, the brain is more susceptible to inflammation than other tissue. Inflammation in the brain is often referred to as neuroinflammation, and it has been linked to many neurological and psychiatric conditions. Antioxidants can protect against inflammation.

Depression & Inflammation:

Researchers found that high CRP levels made patients less responsive to treatment. High levels were also associated with cognitive impairment [1]. There is a strong correlation between C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α with depression and anxiety [2]. The authors stated that lifestyle may be the culprit. Another study found that inhibition of tumor necrosis factor improved sleep quality in depressed individuals [3].

Inflammation interferes with serotonin production

You produce quinolinic acid instead, which is a neurotoxin. This, of course, can be linked to depression. Inflammation is linked to:

Alzheimer’s disease
Autism
Acute depression (and suicide)

Inflammation and cognition

The fact that inflammation increase the production of quinolinic acid makes the connection between inflammation and poor cognition—even linking it to dementia and Alzheimer’s disease [9, 10]. Antioxidants protect against inflammation; indeed, some studies show that antioxidants reduce the chances of developing dementia or Alzheimer’s.

Inflammation and anxiety

An increase in inflammatory markers is common in patients with anxiety disorders [4,5]. One review looked at patients with PTSD and found an increase in IL-6, TNF-alpha, and other inflammatory markers [6].

ADHD and inflammation

Seven studies evaluated the association of cytokine gene polymorphisms in ADHD, and six studies measured cytokines levels in blood. One study analyzed the presence of cytokines in cerebrospinal fluid in patients with ADHD. Altogether, these studies indicate a possible role of inflammation in ADHD pathogenesis, despite the significant heterogeneity and contradictory results [7].

The Microbiome and the Gut–Brain Connection

The microbiome can be a source of inflammation, particularly in patients with ADHD. Studies show that people with ADHD do not always have fewer types of gut bacteria than others. However, they often have different amounts of certain bacteria. Two types that appear important are Bacteroides and Faecalibacterium. These bacteria are involved in communication between the gut and the brain. Changes in these bacteria may affect inflammation in the body and brain, which could influence how the brain works and how ADHD symptoms develop [8].

The Gut-Brain Connection

Prebiotics and probiotics may produce beneficial effects on anxiety and depression [30]. “It is likely that gut microbiota plays a role in depression [31].”
There are bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis [32].
The gut microbiome is different in patients with depression than it is in patients without depression [33].

Insulin Resistance and the Brain

Insulin is not only involved in blood sugar regulation—it also plays an important role in brain function. Neurons use glucose as their primary fuel, and insulin signaling helps regulate energy metabolism in the brain. Metabolic syndrome, which is the result of insulin insensitivity, can have a negative effect on cognition.

When insulin resistance develops, brain cells may not receive energy efficiently. Researchers have linked insulin resistance to:

Depression
ADD/ADHD
cognitive decline
Alzheimer’s disease
impaired memory and concentration

Some researchers have even referred to Alzheimer’s disease as “type 3 diabetes” because of impaired insulin signaling in the brain.

Insulin resistance is also associated with inflammation, oxidative stress, and changes in the gut microbiome—all factors that can influence brain health.

Improving insulin sensitivity through diet, physical activity, and metabolic health may therefore support normal brain function.

The Environment

Environmental chemicals are strongly linked to problems with the thyroid as well as with the brain and nervous system. Research shows that Parkinson’s is often linked with environmental exposures, especially pesticides, industrial chemicals, and air pollution [11-20]. They can have a negative impact not only on the brain, but on the endocrine system, especially the thyroid.

Stress

Stress is very hard on the brain and nervous system (just as it is for every system in the body). There is a strong connection between stress and depression and anxiety. “One of the most enduring and replicated findings in biological psychiatry is activation of the hypothalamic-pituitary-adrenal (HPA) axis in a subset of patients with major depressive disorder [21]”.

Stress has long been associated with anxiety disorders [22-26]. Stress influences the hypothalamic–pituitary–adrenal axis and autonomic nervous system—ultimately affecting the immune system. Chemical changes brought on by chronic stress can lead to inflammation.

Children with ADHD tend to have lower morning cortisol than normal controls [27,28]. They also show reduced hypothalamus-pituitary adrenal (HPA) axis responsiveness to stress [29].

The Thyroid

One of the symptoms of hypothyroidism is depression: See if the other thyroid symptoms are present. “Multiple studies concluded that undiagnosed, untreated, undertreated patients with hypothyroidism are at increased risk of developing depression. Autoimmune thyroiditis is also associated with an increased risk of depression. Elevated thyroid-stimulating hormone (TSH), antithyroglobulin (TgAb), and thyroid peroxidase antibodies (TPOAb) levels have all been linked to depression and an increased risk of suicide. Moreover, hypothyroidism is known to be one of the leading causes of treatment-resistant depression.

The Bigger Picture

Conditions such as ADHD, depression, anxiety, and cognitive decline are often treated as completely separate disorders. However, many of the same biological processes appear to influence all of them. These include inflammation, microbiome imbalance, environmental exposures, chronic stress, hormonal dysfunction, and nutrient deficiencies. Supporting overall brain health may therefore improve multiple symptoms at the same time.

Brain Health, ADHD, Depression & Cognition: The Role of Inflammation, Stress & the Gut–Brain Axis