Neuro(b)log For Patients

Depression is not just about sadness, loss of energy, or a drop in mood. Many people do not realize that depression significantly impacts cognitive functions as well — meaning the way we think, focus, remember information, or make decisions. These changes can be just as debilitating as the mood disturbances themselves. Globally, depression affects approximately 13% of the older population. 

Let's first explain the difference between depression and a so-called "bad mood"

The term "bad mood" became widespread and famous in the Czech Republic thanks to Václav Havel, who used it as a metaphor for society-wide skepticism and fatigue. In everyday life, we use it to describe not only irritability, fatigue, and a feeling of being drained of energy, but also when things go wrong and we have a "bad day," or when we feel overwhelmed. It is simply a state where we can clearly name why we feel this way. Often, this state lasts for hours or a few days and is a normal part of human emotions, which naturally fluctuate throughout life. Sufficient rest, a change of scenery, a change of activity, or sleep usually help. In most cases, it resolves on its own.

Depression is an illness that has its own specific classification code in the International Classification of Diseases (ICD-10) and can significantly impair a person's life. It is a psychological (psychiatric) condition. It affects mood, thinking, energy, sleep, motivation, appetite, bodily functions, and the ability to experience pleasure (anhedonia).Typically, it lasts for two or more weeks, often much longer, without a clear, obvious cause. A person loses interest in things they used to enjoy and experiences feelings of hopelessness, slowed thinking, and fatigue. Depression is often accompanied by sleep disorders, anxiety, and changes in appetite. It disrupts functioning both at work and in private life or relationships. Rest does not bring the desired relief.

What Are Cognitive Functions?

These are the processes that help us focus, plan, organize tasks, remember information, react quickly, solve problems, and make decisions. Executive functions include planning, organization, problem-solving, and emotional self-regulation. Spatial orientation is also categorized among these functions.

Causes of Cognitive Function Impairment:

• Age and brain changes (e.g., neurodegenerative diseases such as Alzheimer's dementia, Parkinson's disease, and others)
• Stress and lack of sleep
• Cerebrovascular diseases (e.g., post-stroke conditions)
• After traumatic brain injuries
• Psychiatric conditions (e.g., depression)
• Social isolation due to a lack of social contact
• Unhealthy lifestyle (e.g., alcohol or drug dependence)

How Depression Affects Thinking

Impaired Concentration
Patients with depression frequently describe difficulties with focusing and maintaining attention. They find it challenging to read, watch a movie, work, or complete a simple ongoing task. This is because the brain is overwhelmed by negative thoughts and no longer has the capacity to utilize for focus.

Difficult Decision-Making
Even a simple choice, such as deciding what to eat or choosing what to do first, becomes exhausting and feels almost like a "Sophie's choice" for a patient with depression. A brain experiencing depression has a reduced capacity to evaluate options and anticipate consequences.

Memory Problems
Depression causes forgetfulness and difficulties in recalling information. In the clinic, patients frequently complain of having "brain fog" or clouded thinking.

Slowed Thinking
Some patients describe that it is hard for them to think, and that it takes them longer to process information or respond to external stimuli. In medicine, this is referred to as a slowed psychomotor tempo.

Negative Cognitive Bias
Depression also changes the way a person views the world. It brings pessimism, the underestimation of one's own abilities, expectations of the worst-case scenarios, and excessive self-blame. All of this is a direct consequence of the illness called depression.

Depression and the Brain

Major depressive disorder is not just a "bad mood." It is an illness that affects the entire body — including the brain. People with severe depression face a higher risk of premature mortality (not only due to suicide) but particularly because of frequent sleep disturbances and an increased incidence of cardiovascular diseases.In recent years, research has shown that inflammation in the brain, known as neuroinflammation, plays a major role in the development of depression.

What Is Neuroinflammation and Why Is It Important?

During severe depression, an abnormal inflammatory response occurs in the brain. Various types of brain cells are involved in this reaction:

• microglia — the "immune cells" of the brain,
• astrocytes — cells that support the nutrition and function of neurons,
• oligodendrocytes — cells that form the protective myelin sheath of nerves,
• and other immune cells that can penetrate through the blood-brain barrier.

These cells enter the brain regions affected by inflammation and can disrupt its normal functioning.

What Happens in the Brain During Depression?

Severe depression is linked to several neurobiological changes:

1. Reduced Serotonin Levels

Serotonin is a substance that influences mood, sleep, and appetite. Its deficiency is one of the reasons why a person feels despondent and lacks energy.

2. Disruption of the Stress Axis (Hypothalamus–Pituitary–Adrenal Axis)

This axis controls the body's response to stress. In depression, it can become overloaded or malfunction, leading to fatigue, anxiety, and other difficulties.

3. Impaired Generation of New Neurons

In a part of the brain called the dentatus gyrus (a component of the hippocampus), new nerve cells continue to form even in adulthood — a process called neurogenesis. In depression, this process is slowed down or disrupted.This has a direct impact on:

• memory,
• learning ability,
• emotional regulation,
• resilience to stress.

4. Decrease in Neurotrophic Factors

Neurotrophic factors are substances that support the growth and regeneration of neurons. In depression, their levels tend to be reduced, which may explain why the brain struggles to "recover" and why the hippocampus is visibly smaller in some patients.

5. Structural Brain Changes

Patients currently suffering from depression, as well as those at an increased risk of developing it, exhibit functional and structural brain abnormalities precisely in the area known as the prefrontal cortex.

What This Means for Future Treatment

Research shows that depression is a much more complex illness than previously thought. It is not just a simple "chemical imbalance," but a combination of:

• inflammatory processes,
• hormonal changes,
• disrupted neurogenesis,
• alterations in neurotransmitters.

Because of this, current research focuses on finding new treatment methods that can:

• reduce inflammation in the brain,
• support the growth of new neurons,
• increase the levels of neurotrophic factors.

These approaches are currently in the research stage, but they hold great promise for future treatment options.

The "Gut-Brain" Axis (Gut-Brain Axis)

As mentioned earlier in the article, individuals with depression experience impairments in cognitive functions, attention, or executive functions. Lately, the general public has frequently heard the phrase "gut-brain axis" or the concept that the microbiome — meaning the bacteria in the gut — influences mood.

Let's explain what this actually means. You can visualize it as a complex network connecting the digestive tract, gut bacteria, the brain, and the vagus nerve (nervus vagus), along with the immune and hormonal systems. All of these components communicate with each other on various levels, thereby impacting mood, psychological distress (anxiety), stress responses, the immune and digestive systems, and, last but not least, memory and cognitive functions.

How the Microbiome Influences the Brain

Gut bacteria do not just exist passively in the digestive tract. They are an integral part of producing certain vitamins (like B12) as well as other compounds, such as neurotransmitters (serotonin, dopamine, GABA = gamma-aminobutyric acid, acetylcholine). Few laypeople know that up to 90% of serotonin is produced in the gut. While digesting fiber, oligosaccharides, and plant polysaccharides, the bacteria in the large intestine produce short-chain fatty acids (SCFAs). These support the health of the intestinal wall and the brain, and they actively counteract inflammatory processes.The microbiome also participates in regulating the immune system, as up to 70% of all immune cells reside in the gut. A specific group worth mentioning is innate lymphoid cells (ILCs). They regulate inflammation by producing cytokines, support healing, maintain the balance of the microbiome, and help keep the gut mucosa healthy. 

According to clinical studies conducted so far, changes in intestinal permeability and impaired gut microbiome function have been demonstrated in patients with autoimmune diseases such as multiple sclerosis, Crohn's disease, rheumatoid arthritis, and others.Chronic inflammation in the gut caused by an imbalance (dysbiosis) is transmitted to the brain as neuroinflammation, which is precisely what is described in cases of depression.

And how does the vagus nerve (nervus vagus) fit into all of this? 

Part of the enteric nervous system of the gut is the plexus myentericus (Auerbach's plexus), which is sometimes referred to as the "second brain." It is located between the muscular layers of the gut and controls intestinal movement (peristalsis) — i.e., the contractions of the intestinal muscles — regulates the speed of digestion, and responds to chemical and mechanical stimuli in the gut. It operates entirely independently while simultaneously communicating with the brain. This is because it contains the exact same neurotransmitters as the brain (dopamine, serotonin, and acetylcholine).The vagus nerve is the main nerve of the parasympathetic nervous system and transmits signals directly from the gut to the brain. Its function therefore has a major impact on mood, stress responses, and the development of anxiety. Of course, it is most widely known for its ability to regulate heart rate, breathing, and digestion. It responds directly to substances produced by gut bacteria. Notably, 80–90% of the information travels upward from the gut to the brain.Research suggests that patients with depression frequently have disrupted communication via the vagus nerve, and stimulating it can lead to an improvement in depressive symptoms. 

However, further clinical trials and research are required to effectively utilize the potential of vagus nerve stimulation. Currently, vagus nerve stimulation is already used as a treatment for refractory epilepsy. An imbalance in the gut microbiome can affect mood through these signals sent from the gut to the brain. Studies indicate a potential positive effect of probiotics on improving certain cognitive functions, such as memory, in people with depression. 

Additionally, so-called psychobiotics may alleviate anxiety and depressive symptoms. However, it is essential to keep in mind that probiotics do not replace medications for depression (antidepressants). A diet rich in fiber, fermented foods, and a varied nutritional intake naturally supports a healthy microbiome.

When to See a Specialist

If the condition lasts longer than two weeks, worsens, or interferes with daily life, it is advisable to turn to a doctor or a psychologist. Timely help can prevent the development of a more severe form of depression.

Conclusion

Depression is an illness whose biological causes include not only biochemical processes in the brain but also neuroinflammation and other brain function impairments. The consequences are the symptoms of depression, which include cognitive impairment, not just mood disturbances. In my clinic, I meet many patients diagnosed with depression that accompanies various other neurological conditions. Migraine, tension headaches, chronic pain, dementia, epilepsy, and functional movement disorders are just a few examples of diagnoses where symptoms of depression can occur hand in hand with the primary illness. These patients require care on a multidisciplinary level (psychiatrist, neurologist, psychologist).Depression is treatable, and therefore, if you suspect you have depression or another psychiatric illness, contact a specialist.If your psychiatrist has recommended a neurological evaluation, you can schedule an appointment at my neurology clinic in Brno.

MUDr. Petra Mištríková, MBA

References:

Wu A, Zhang J. Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis. J Neuroinflammation. 2023 Nov 27;20(1):283. doi: 10.1186/s12974-023-02964-x. PMID: 38012702; PMCID: PMC10683283.

Pizzagalli DA, Roberts AC. Prefrontal cortex and depression. Neuropsychopharmacology. 2022 Jan;47(1):225-246. doi: 10.1038/s41386-021-01101-7. Epub 2021 Aug 2. Erratum in: Neuropsychopharmacology. 2022 Jan;47(2):609. doi: 10.1038/s41386-021-01160-w. PMID: 34341498; PMCID: PMC8617037.

Price RB, Duman R. Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model. Mol Psychiatry. 2020 Mar;25(3):530-543. doi: 10.1038/s41380-019-0615-x. Epub 2019 Dec 4. PMID: 31801966; PMCID: PMC7047599.

Schneider E, Doll JPK, Schweinfurth N, Kettelhack C, Schaub AC, Yamanbaeva G, Varghese N, Mählmann L, Brand S, Eckert A, Borgwardt S, Lang UE, Schmidt A. Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial. J Psychiatry Neurosci. 2023 Jan 18;48(1):E23-E33. doi: 10.1503/jpn.220117. PMID: 36653035; PMCID: PMC9854921.

Nouari W, Aribi M. Innate lymphoid cells, immune functional dynamics, epithelial parallels, and therapeutic frontiers in infections. Int Rev Immunol. 2025;44(5):245-272. doi: 10.1080/08830185.2025.2490233. Epub 2025 Apr 17. PMID: 40242974.

Austelle CW, O'Leary GH, Thompson S, Gruber E, Kahn A, Manett AJ, Short B, Badran BW. A Comprehensive Review of Vagus Nerve Stimulation for Depression. Neuromodulation. 2022 Apr;25(3):309-315. doi: 10.1111/ner.13528. Epub 2021 Sep 6. PMID: 35396067; PMCID: PMC8898319.

Austelle CW, Cox SS, Wills KE, Badran BW. Vagus nerve stimulation (VNS): recent advances and future directions. Clin Auton Res. 2024 Dec;34(6):529-547. doi: 10.1007/s10286-024-01065-w. Epub 2024 Oct 4. PMID: 39363044; PMCID: PMC11543756.

Share