A Review of the Relationship of the Cerebrospinal Fluid Changes During the Dysregulation of Parathyroid Hormone With Psychiatric or Neurological Manifestations

Abstract

It is established that normal calcium and vitamin D concentrations are maintained in the body through parathyroid hormone (PTH), a signaling molecule secreted from parathyroid glands. A massive role is played by PTH in increasing calcium levels when they are extremely low in the body through different mechanisms. The dysregulation of this hormone is due to either over functioning of the gland (hyperparathyroidism) or compromised functioning in hypoparathyroidism. A detailed review was done to identify if any changes are happening in the cerebrospinal fluid (CSF) due to any pathology causing the parathormone to be dysregulated enough to, in turn, cause any further pathology in the nervous system. This may then lead to various disabling neuropsychiatric features. The calcium and vitamin D abnormalities are both directly and indirectly connected to psychiatric features like delusions, schizophrenia, disabled cognition, psychosis, coma, mania, and depression of all kinds. Moreover, their irregularities are also linked to Alzheimer's. During these manifestations, the CSF is altered concentration-wise, where elevated calcium levels inside are observed during different studies. Despite PTH's indirect connection to the CSF modifications, their association hasn't been potently proven yet, considering more observational studies should be conducted in humans and for a more extended period, along with bigger and greater numbers of CSF samples. Suppose there is a possibility of the link of CSF alterations to PTH. In that case, we can consider a pronounced increase of CSF calcium or PTH as a risk factor for debilitating neuropsychiatric diseases. In this review, the possible correlation of CSF and PTH has been discussed.

Gene expression profiling in peripheral blood lymphocytes for major depression: preliminary cues from Chinese discordant sib-pair study

“…The normal level of calcium and vitamin D in the human body is maintained by parathyroid hormone (PTH). The abnormality of calcium and vitamin D is directly or indirectly related to psychiatric features such as delusion, schizophrenia, cognitive impairment, mental illness, coma, mania, and various depressions [ 33 ]. In patients with depression, the conversion of tryptophan in the brain stops due to disregulation of parathyroid hormone, which produces little or no serotonin, further contributes to a defective mental state, changed cognition, and false sensory gait [ 33 ].…”

“…The abnormality of calcium and vitamin D is directly or indirectly related to psychiatric features such as delusion, schizophrenia, cognitive impairment, mental illness, coma, mania, and various depressions [ 33 ]. In patients with depression, the conversion of tryptophan in the brain stops due to disregulation of parathyroid hormone, which produces little or no serotonin, further contributes to a defective mental state, changed cognition, and false sensory gait [ 33 ]. Defects in the processing of PTH may lead to hypoparathyroidism, resulting in hypocalcemia and numbness, which can cause psychiatric disorders.…”

Successful parathyroidectomy improves cognition in patients with primary hyperparathyroidism: A prospective study in a tertiary medical center and comprehensive review of the literature

“…Another study (which did not focus on patients with primary hyperparathyroidism) did not show any relation between elevated PTH levels and progressive cognitive decline over 20 years as evaluated by three tests (Delayed Word Recall, the Digit Symbol Substitution, and the Word Fluency tests) and a compound Z score ( 48 ). On the other hand, analyses of calcium and monoamine in the cerebral spine fluid were found to correlate with neurocognitive impairment and improvement after surgery ( 49 , 50 ); data from a recent review did not demonstrate that changes in CSF could be related to neurocognitive symptoms ( 51 ).…”

Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System

“…Controversial and old data are present in the literature regarding PTH crossing the blood-brain-barrier (BBB) [16]. PTH has been found in the cerebrospinal fluid (CSF) [17], and a recent review summarized data about the association between changes in the levels of PTH in the CSF and the incidence of neuropsychiatric disorders in patients [18]. An intriguing but so far undemonstrated hypothesis postulates that a small intracerebral secretion of PTH could occur due to the similarities between parathyroid cells and neuroectodermally-derived APUD cells in the brain, and the sequence homology between PTH and the neuropeptide proopiomelanocortin (POMC) [19].…”