Page 8 - JCBP-2-4

Journal of Clinical and
Basic Psychosomatics FND and gut microbiome

its symptomatology cannot be explained by any other networks. In recent decades, new hypotheses on the
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psychological or physiological condition. The main pathophysiology of these disorders have been formulated
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symptoms of FND include abnormal movements, aphasia, based on the integration of psychology and neurobiology,
blindness, deafness, dizziness, localized anesthesia, muscle taking into account the neuropsychobiological factors
weakness, paralysis, pseudoseizures, psychogenic non- that contribute to the development and maintenance of
epileptic seizures, speech difficulties, and tremors. 10,11 FND. 28,29
The origin of this disorder is not yet fully understood, Few studies have placed the focus on the molecular
although several predisposing, precipitating, and basis of FND. The current evidence highlights the presence
perpetuating factors have been reported as possible of altered levels of the neurotransmitter glutamate in the
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consequences of its etiology. However, there is an limbic system and in the cerebrospinal fluid of patients with
association between the development of FND and the life FMD, a specific subtype of FND. 30,31 In addition, another
event stressors during childhood that lead to trauma. 13,14 neurotrophin, the BDNF, is involved in the development,
It is well known that trauma affects salience, emotion survival, maintenance, and plasticity of neurons, and has
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processing, and sensorimotor circuitry in the brain. been related to the pathophysiology of FND, as patients
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On the other hand, event stressors may be caused by with epileptic and psychogenic non-epileptic seizures have
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external stimuli, physiological illnesses, or psychological decreased serum BDNF levels. More recently, Demartini
pressures, and regarding these states, there is comorbidity et al. reported lower blood levels of glutamate, BDNF, and
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with other neuropsychiatric disorders, including anxiety, dopamine in FMD patients compared to healthy controls
dissociative disorders, post-traumatic stress disorder, and and concluded that glutamatergic and dopaminergic
depression. 16,17 dysfunction may be involved in the pathophysiology of
FMD.
FND symptoms result from complex interactions
involving the central nervous system (CNS), endocrine, and Another factor that may contribute to the
immune systems. Especially, the hypothalamic-pituitary- pathophysiology of FND is oxidative stress, which
adrenal (HPA) axis plays a crucial role, as its dysfunction is provokes damage in the brain through the production
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influenced by prolonged psychological stress. As a result, of reactive oxygen species (ROS). Oxygen derivatives
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stress hormones, such as cortisol, can have detrimental and peroxides have been implicated in the harmful
effects on immune function, inflammation, and overall mechanisms of several neuropsychiatric disorders, such as
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balance within the organism. 19 anxiety, depression, and schizophrenia. However, various
markers of oxidative stress, including ROS, 8-isoprostane,
There are studies that have investigated the effects of
psychological stress on the gut microbiome. In addition, thiols, and nitrite derivatives, have not yet been evaluated
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in FND.
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the gut microbiome influences brain function and behavior
through the gut-brain axis, and its dysbiosis can potentially The potentiality that inflammation plays a role within
lead to the development of various psychological and the pathophysiology of FND may provide feedback
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psychiatric disorders. Therefore, in this work, we regarding how trauma and stressful events during
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hypothesized the relationship between the gut microbiome childhood adversely affect the adult’s health. It is well
and the pathophysiology of FND because gut microbiome known that stress provokes inflammation, 40,41 mainly by
dysbiosis and FND share several common features, such causing an imbalance in the homeostatic mechanisms,
as the effects of neurotransmitters, the hippocampal ultimately leading to the release of glucocorticoids through
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expression of brain-derived neurotrophic factor (BDNF), the HPA axis, and there is a hyperarousal stress state in
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and inflammatory responses. 24 the FND motor-related symptoms. 43
2. Pathophysiology of FND 3. Microbial neurotransmitters and
metabolites
Frequent manifestations of FND include functional
seizures (also known as dissociative or psychogenic Gut microbes regulate several host functions and behavior
non-epileptic seizures), functional movement disorders through chemical interactions with the CNS, including both
(FMDs) (paresis), somatosensory or visual symptoms, and “direct” and “indirect” communication. Microorganisms
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speech disorders. Brain differences (gray matter and basal have the ability to produce various neurotransmitters,
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ganglia volumes) have been found in FND individuals such as acetylcholine, dopamine, gamma-aminobutyric
compared to healthy controls. FND individuals show acid, norepinephrine, and serotonin (Table 1), which can
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increased connectivity between the insula, motor, and stimulate host production of other neuroactive compounds
parietal areas and abnormalities in agency and limbic that regulate gut-brain signaling. Therefore, dysbiosis
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Volume 2 Issue 4 (2024) 2 doi: 10.36922/jcbp.4160