Vitamin D deficiency is a re-emerging epidemic, especially in minority populations. Vitamin D is crucial not only for bone health but for proper brain development and functioning. Low levels of vitamin D are associated with depression, seasonal affective disorder, and schizophrenia in adults, but little is known about vitamin D and mental health in the pediatric population.
One hundred four adolescents presenting for acute mental health treatment over a 16-month period were assessed for vitamin D status and the relationship of 25-OH vitamin D levels to severity of illness, defined by presence of psychotic features.
Vitamin D deficiency (25-OH D levels <20 ng/ml) was present in 34%; vitamin D insufficiency (25-OH D levels 20–30 ng/ml) was present in 38%, with a remaining 28% in the normal range. Adolescents with psychotic features had lower vitamin D levels (20.4 ng/ml vs. 24.7 ng/ml; p = 0.04, 1 df). The association for vitamin D deficiency and psychotic features was substantial (OR 3.5; 95% CI 1.4-8.9; p <0.009). Race was independently associated with vitamin D deficiency and independently associated with psychosis for those who were Asian or biracial vs. white (OR = 3.8; 95% CI 1.1‒13.4; p < 0.04). Race was no longer associated with psychosis when the results were adjusted for vitamin D level.
Vitamin D deficiency and insufficiency are both highly prevalent in adolescents with severe mental illness. The preliminary associations between vitamin D deficiency and presence of psychotic features warrant further investigation as to whether vitamin D deficiency is a mediator of illness severity, result of illness severity, or both. Higher prevalence of vitamin D deficiency but no greater risk of psychosis in African Americans, if confirmed, may have special implications for health disparity and treatment outcome research.
Vitamin D; Adolescents; Deficiency; Psychosis
Vitamin D deficiency is endemic across the life span and in diverse populations throughout the world . Contributing factors are lack of exposure to sunlight and insufficient dietary intake; individuals with darker skin are at higher risk due to low cutaneous synthesis and dairy-poor diets. In a study of healthy Northeastern US adolescents, more than 90% of African American teens and 55% of all teens had low vitamin D . The National Health and Nutritional Examination Survey (NHANES 2001–2004) found an overall US prevalence of vitamin D insufficiency in adolescents of 61%, with 9% deficient .
Vitamin D is well recognized as essential for intestinal calcium absorption, serum calcium homeostasis, optimal skeletal development, and the prevention of rickets and osteoporosis . The importance of vitamin D to the CNS in both healthy and psychiatric populations is less well-appreciated and is vastly understudied compared to its known impact on bone health. Vitamin D receptors are present throughout the brain, and D-deficiency is associated with negative CNS effects in animal studies . Vitamin D receptors and activating enzymes are particularly prominent in the hypothalamus and substantia nigra, and are involved in glucocorticoid signaling in hippocampal cells. Depletion models show maternal offspring with abnormal brain shape, cell number, and reduced neurotropic factors and receptors. Vitamin D receptor animal knock-out models show increased anxiety, decreased activity, and muscular and motor impairments, resembling phenotypic models of depression. Vitamin D is neuroprotective to hippocampal cells, through regulating calcium ion channels and activating PKC and mapPK pathways.
Clinical studies reinforce the significance of this basic work. A Finnish cohort supplemented with prenatal and infant vitamin D demonstrated reduced adult risk for schizophrenia . Low vitamin D levels were found to correlate with major depression  and premenstrual mood symptoms in women , and mood disorders and cognitive impairment in older adults . Two randomized controlled trials (RCT) have shown that raising vitamin D levels improved depression. The first study examined phototherapy vs. vitamin D supplementation for seasonal affective disorder, and found a positive effect for vitamin D via either supplementation or phototherapy within one month. Another RCT of overweight and obese subjects, at greater risk for low vitamin D than those of normal weight, found higher levels of depression with low vitamin D; supplementation resulted in significant improvement in depressive symptoms after one year . To the best of our knowledge, there have been no published studies examining vitamin D deficiency and the presence of psychosis in adolescents.
We hypothesized that, in severely mentally ill adolescents, defined as adolescents requiring either inpatient or partial hospitalization, 1) rates of vitamin D insufficiency and deficiency would be greater than those documented in general US populations, and 2) lower vitamin D levels would be associated with mental illness severity, defined as presence of psychotic features.
Methods and Materials
The University of Rochester Research Subject Review Board approved the retrospective chart review study.
The study population included 75 females and 29 males aged 12 to 18 years admitted to the Strong Behavioral Health Child and Adolescent Acute Inpatient Service or Partial Hospitalization Service (CAPHS), Department of Psychiatry, University of Rochester, NY, between October 2008-February 2010 who had serum 25-OH vitamin D levels collected on routine admission laboratory testing as part of a quality improvement initiative.
Charts were identified by a clinical admission database of the service. Diagnostic evaluations and symptom reports from parents/legal guardians and adolescents were extracted from medical records for the period of clinical care.
Clinical DSM-IV diagnoses were predominantly affective disorders (bipolar disorders, N = 37; depressive disorders, N = 36; mood disorder NOS, N = 15; psychotic disorders, N = 8; anxiety disorders, N = 4; and ADHD/ODD N = 1).
Patient-reported psychosis and potentially related variables
Psychotic symptoms, defined as hallucinations, paranoia, or delusions, were documented on standardized admission assessment forms by the emergency room psychiatrist and the admitting attending. They were categorized dichotomously as yes/no by the second author (TLF), who was blinded to both the purpose of the study and to vitamin D levels until after record extraction was completed. Other variables examined included: race, month of admission/vitamin D level, insurance status, urban/suburban/rural residence, inpatient/partial hospital outpatient, clinical DSM-IV diagnosis, smoking status, age of onset of mental illness, admitting medications, past medications, and immediate and extended family psychiatric and medical history.
Vitamin D laboratory analysis and categorical definitions
Vitamin D 25-OH (25OHD) levels were analyzed by chemiluminescent immunoassay at ARUP laboratories, SLC, Utah, and recorded as normal if >30 ng/ml, insufficient if 20–30 ng/ml, and deficient if <20 ng/ml, as per expert guidelines .
Continuous data were graphically inspected for distributional assumptions; comparisons between the normal, insufficient, and deficient vitamin D groups were evaluated by ANOVAs (with t-tests subsequent to the overall analysis), Wilcoxon rank sum test, χ², or Fisher’s exact test, as appropriate to the data. The relationship of vitamin D levels and psychosis was assessed with an ANOVA type design and the association of psychosis with vitamin D level groups with logistic regression models, assessing race as well as vitamin D level groups in a multivariate model. All analyses were carried out using SAS 9.2 on a Windows 7 platform.
Vitamin D deficiency prevalence and association with psychosis
Thirty-five (33.7%) adolescents were vitamin D deficient (<20 ng/ml), and an additional 40 (38.4%) were vitamin D insufficient (20–30 ng/ml). Of those with vitamin D deficiency, 40% had psychotic features compared to only 16% of the sample who were not vitamin D deficient (p < 0.007). Those with D deficiency were 3½ times more likely to have psychotic features (OR 3.52, CI 1.38-8.95, 1df). Of those with normal vitamin D status, 79% (N = 23/29) did not have psychotic features.
Demographic and other related variable differences
A comparison of demographic variables between adolescents with insufficient, deficient, and normal 25-OH D levels is presented in Table 1.
Table 1. Patient Characteristics by 25-OH Vitamin D Levels
Those who were deficient were more likely to be black or Asian (Figure 1) and have psychotic features (Figure 2). Figure 3 displays the association of 25-OH vitamin D and the interaction of race and psychosis. All groups showed lower 25-OH D levels in the presence of psychosis including Asians who were all deficient. Asian (N = 5) and biracial (N = 7) categories were combined into the “Other” category and Hispanic/Latino ethnicity (N = 1) was combined with Caucasian in the linear modeling that was conducted. Odds ratio comparisons for presence of psychosis with vitamin D deficiency as well as potential covariates, including race and medication exposure, are depicted in Table 2. Psychosis was independently related to race for the “other” group (Asian and biracial individuals) vs. white group, but not for black vs. white groups, nor significantly associated for other vs. blacks. The association of psychosis and vitamin D level was significant overall in the univariate and multivariable analyses. Of added interest was the association of psychosis with Vitamin D levels and race (Table 3). While race and vitamin D levels were associated, race and psychosis were not associated adjusting for vitamin D levels.