'Calcium Imbalance' Linked to Bipolar Severity

Liam Davenport

May 11, 2021

Calcium homeostasis may play a role in bipolar disorder (BD) severity, with raised serum vitamin D and parathyroid hormone (PTH) levels linked to worse clinical outcomes and high psychological burden, new research suggests.

After measuring serum PTH, vitamin D, and calcium levels in patients with type I or type II BD, investigators found that the number of hospitalizations and prior psychiatric episodes was significantly associated with PTH levels.

In addition, increased PTH levels were highly correlated with levels of emotional and physical abuse and neglect.

"The results suggest that calcium imbalance may influence the long-term outcome of bipolar disorder," lead investigator Carmela Palummo, Department of Psychiatry, University of Campania "Luigi Vanvitelli," Naples, Italy, said during the virtual European Psychiatric Association (EPA) 2021 Congress.

The findings also highlight the importance of routinely assessing PTH, vitamin D, and calcium levels in patients with BD as a marker of clinical severity ― and may point to vitamin D "as a valid add-on treatment for these patients," Palummo added.

Unexplored Area

Vitamin D influences mood and its fluctuations via the modulation of neurotransmitter biosynthesis. In conjunction with PTH, vitamin D also plays a central role in calcium homeostasis, Palummo noted.

Although previous studies have identified an association between vitamin D deficiency and BD severity, few have investigated the impact of alterations in calcium homeostasis on the course of the disorder, she added.

For the current study, investigators assessed calcium homeostasis in 199 patients with type I (54.8%) or type II BD. All were between 18 and 65 years of age (mean age, 47.1 years) and did not have comorbid neurologic disorders or substance abuse; 50.8% of the participants were women.

Baseline measures included clinical and demographic characteristics, as well as plasma levels of calcium, vitamin D, and PTH. Participants were administered a series of disease rating scales, including the Young Mania Rating Scale and the Hamilton Rating Scales for Anxiety and Depression.

Results showed that serum PTH levels were directly correlated with total number of hospitalizations, as well as the number of depressive (P < .0001), manic (P < .001), and hypomanic episodes (P < .01).

Strong correlations were also found between increased PTH levels and emotional neglect, emotional abuse, physical abuse, physical neglect, and total scores on the Childhood Trauma Questionnaire–Short Form (P < .0001).

Serum vitamin D levels were positively associated with age at first psychiatric contact and were inversely correlated with total number of depressive episodes (P < .05) and a cyclothymic temperament (P < .05).

Difficult to Diagnose

Commenting on the findings for Medscape Medical News, Samoon Ahmad, MD, clinical professor, Department of Psychiatry, NYU Langone Health, New York City, described the study as "very interesting" and noted that although the link between vitamin D levels and mental health has been well studied, there has been "far less talk about calcium homeostasis."

Aside from a lack of a control group and small study size, a big issue for other studies that have examined links between vitamin D and depression "has been the question of directionality," said Ahmad, who was not involved with the research.

He pointed out that "most people get the majority of their vitamin D from the sun" but that individuals with depression may not go out into the sun very often. "Is the depression causing someone to go outside less and thereby leading to a vitamin D deficiency? Or is the vitamin D deficiency causing depression?" Ahmad asked.

He added that BD is "difficult to diagnose, and there has been limited research into biomarkers that can help us identify the illness or really gauge" its severity.

Consequently, if future studies involving a control group show that "elevated PTH levels are clearly associated with the disorder and not with other confounding factors, this could be a major breakthrough," said Ahmad.

"I would be very interested in seeing if calcium imbalances can be corrected using supplemental vitamin D or other means and then looking at whether or not patients' symptoms improve," he said.

"If they do improve, this would be a very affordable and easily available option," he noted.

Even if symptoms do not improve with vitamin D supplementation "but we still see a strong enough correlation between elevated PTH levels and bipolar disorder, this means we could use that data to get a more accurate diagnosis," Ahmad added.

Portions of the findings were published previously in Brain Sciences. The study authors and Ahmad have reported no relevant financial relationships.

European Psychiatric Association (EPA) 2021 Congress: Abstract O019. Presented April 10, 2021.

Brain Sci. Published online July 1, 2020. Full article

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