Mental disorders: recent studies point to brain inflammation

Reminder: what is inflammation?

Inflammation is a normal immune reaction triggered in response to an external or internal attack on tissues (1).

This may be of chemical, traumatic, toxic or microbial origin, such as an injury, an infection or an allergen.

It involves white blood cells (leukocytes) on the front line, guided by a set of messengers (prostaglandins, leukotrienes, etc.) that facilitate their influx into the affected area.

When it is short-lived (acute inflammation), it is a useful, if not essential, defensive mechanism for maintaining our physical integrity.

However, it becomes problematic when it persists and remains ‘in the background’: this is known as chronic inflammation, or low-grade inflammation (2). Various factors, such as stress, smoking, a diet rich in sugar, saturated fats and additives, a sedentary lifestyle and a lack of sleep, tend to maintain it.

It has already been established that a chronic inflammatory state is the breeding ground for many autoimmune and metabolic diseases, such as type 2 diabetes (3).

But what about mental and psychiatric disorders? Are they also correlated with silent inflammation? Researchers are now answering in the affirmative...

Two new studies point to a link between cerebral inflammation and mental health

A comprehensive review published in January 2025 explored in greater detail the nature of the links between neuroinflammation and depression (4).

This particularly complex relationship is thought to be bidirectional.

On the one hand, cerebral inflammation is thought to precipitate the onset of depressive symptoms via various mechanisms: an increase in pro-inflammatory cytokines, activation of the hypothalamic-pituitary-adrenal (HPA) axis involved in the production of cortisol (the ‘stress hormone’) and altered synthesis of serotonin (the ‘happiness hormone’).

On the other hand, chronic stress activates microglia, the immune cells that reside in the central nervous system, and triggers the release of inflammatory mediators (IL-1β, TNF-α).

By disrupting neurotransmission and neuroplasticity, these inflammatory mediators predispose individuals to mood disorders, paving the way for a formidable vicious circle.

The second review, published in February 2025, examines the role of neuroinflammation in the development and progression of schizophrenia (5).

One of the studies mentioned, involving 41 patients with acute psychosis and schizophrenia, again revealed a significant increase in certain pro-inflammatory cytokines, notably IL-6, IL-2R and IL-8, compared with the control group.

A positive correlation was also found between symptom severity and IL-6 and IL-2R levels.

This inflammatory 'surge' could partly explain the changes in the metabolic pathways of dopamine, glutamate and tryptophan that are characteristic of this disease.

To sum up: what is the link between cerebral inflammation and mental disorders?

In the light of previous studies and current knowledge, it seems that cerebral inflammation may affect mental health in a number of ways:

• reduced serotonin synthesis: certain inflammatory molecules are thought to prevent the conversion of tryptophan into serotonin, which plays a role in mood regulation, in favour of neurotoxic compounds (such as quinolinic acid) (6);
• glutamate–GABA imbalance: clinical and preclinical data show deficits in glutamate and GABA signalling in major depressive disorder, likely to modify behavioural responses (7);
• excess glucocorticoids: a recent hypothesis raises the question of a direct pro-inflammatory effect of cortisol, which would perpetuate a cycle of stress and depression by affecting, in particular, the region of the hippocampus linked to emotional regulation (8);
• activation of microglia: immune cells in the brain, stimulated by inflammatory substances or stress, are thought to release free radicals and cytokines that fuel local inflammation and alter neuronal circuits (9).

However, it would be simplistic to see neuroinflammation as the sole cause of mental disorders, which also depend on genetic, psychosocial and environmental factors.

Natural solutions to combat brain inflammation?

Complementary natural approaches are helping to curb inflammation levels at both cerebral and systemic levels.

It appears that regular physical activity and a balanced diet rich in antioxidants and healthy fatty acids, such as the Mediterranean diet or the MIND diet (originally created to prevent cognitive decline), have a positive effect on mental health (10-11).

At the same time, certain substances are recognised for their ability to modulate the inflammatory response and/or directly support brain and mental health.

Among minerals, magnesium ranks first: by regulating the glutamate-GABA balance, it contributes to the normal functioning of the nervous system and normal psychological function (12). When supplemented, magnesium threonate (used in Magnesium Threonate) is particularly well absorbed by brain tissue, due to its ability to cross the blood-brain barrier (13).

The importance of omega-3 fatty acids in mediating cerebral inflammation also seems to be confirmed. In particular, studies suggest that EPA (eicosapentaenoic acid) supplementation could reduce certain inflammatory markers in people with depression (14). Highly-dosed supplements (such as Super EPA) make it easy and effective to optimise intakes.

Extracted from green tea, L-theanine is an amino acid that has attracted the attention of brain nutrition researchers for its supposed relaxing and tranquillising properties. In rats, it has been shown to have an anxiolytic effect by modulating hippocampal activity and glutamate levels (see also L-Theanine) (15).

Thanks to its curcuminoid content, turmeric is one of the most powerful natural anti-inflammatories and antioxidants (16). Its synergistic association with other compounds such as nettle or cat's claw, which support the immune system, broadens its spectrum of action (InflaRelief, which is entirely dedicated to inner balance, combines these 3 extracts with 9 other natural nutrients, including boswellia, tulsi and rosemary, among others) (17).

We've already mentioned its name several times, and with good reason: GABA, or gamma-aminobutyric acid, is the main inhibitory neurotransmitter in the central nervous system. Its main function is to delay the effects of glutamate in order to reduce neuronal excitability. It is therefore generally associated with a return to calm and serenity. This explains why people who are stressed or depressed frequently report experiencing better emotional management when they supplement with GABA (note that the liposomal form presented in Liposomal GABA is the one that offers the best bioavailability) (18).