Functional Neurological Disorder: How Early Life Trauma Can Contribute

A new study led by investigators at Massachusetts General Hospital examined the brains of individuals who experienced early-life trauma, some with functional neurological disorder (FND) and others without the condition.

“Motor and limbic circuits were more strongly interconnected in individuals with FND reporting a greater severity of childhood physical abuse,”

said lead author Ibai Diez, Ph.D., an MGH senior research fellow in Neurology and Radiology. This finding may lead to potentially important insights on the plastic brain mechanisms involved in promoting higher communication between motor control circuits and emotion processing circuits.

Early-life Maltreatment

In functional neurological disorder, the brain generally appears structurally normal on clinical MRI scans but functions incorrectly – like a computer software glitch – resulting in patients experiencing symptoms including limb weakness, tremor, gait abnormalities and non-epileptic seizures. In some cases, childhood maltreatment may have been a contributing factor, yet links between risk factors such as childhood abuse and brain mechanisms for the development of FND remain poorly understood.

The study involved 30 adults with FND and 21 individuals whose clinical depression diagnoses served as controls.

Some of the participants in both groups had experienced early-life maltreatment, as determined through questionnaires. In FND patients only, differences in the severity of childhood physical abuse correlated with differences in connections between certain regions of the brain — for example, between the limbic regions which control emotions, arousal and survival instincts among other functions, and the primary motor cortex which is involved in voluntary movements.

Transcriptional Gene Expression

In additional assessments, investigators examined how the expression of genes in a publicly available data set from the Allen Institute related to brain areas showing prominent plastic effects correlated to the degree of early-life physical abuse in patients with FND.

As background, some genes in the literature have been shown to increase risk for developing brain disorders after experiencing early-life maltreatment. The researchers found that brain areas showing prominent functional re-organization in patients with FND were the same brain areas highly expressing genes involved in neuroplasticity and nervous system development.

“Our study has potential implications regarding our understanding of brain-trauma relationships not only in patients with FND but also across the greater spectrum of trauma-related brain disorders,”

explained senior author David Perez, MD, MMSc.

Perez stressed that although childhood maltreatment may be a risk factor for the development of FND in some individuals, there are many social, environmental, and biological factors that likely influence the development of FND later in life.

[1] Diez, I., Larson, A.G., Nakhate, V. et al. Early-life trauma endophenotypes and brain circuit–gene expression relationships in functional neurological (conversion) disorder. Mol Psychiatry (2020). https://doi.org/10.1038/s41380-020-0665-0


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