Wednesday, August 23, 2023

Iron and tic disorders

Inspired by a patient

Avrahami M, Barzilay R, HarGil M, Weizman A, Watemberg N. Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study. J Child Adolesc Psychopharmacol. 2017 Mar;27(2):192-195. doi: 10.1089/cap.2016.0069. Epub 2016 Aug 22. PMID: 27548271.


Objectives: Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder.

Methods: Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic.

Results: Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups.

Conclusion: Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

Ghosh D, Burkman E. Relationship of serum ferritin level and tic severity in children with Tourette syndrome. Childs Nerv Syst. 2017 Aug;33(8):1373-1378. doi: 10.1007/s00381-017-3424-z. Epub 2017 May 3. PMID: 28470381.


Purpose: Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS.

Methods: Children <18 years, diagnosed with TS during 2009-2015, were reviewed. Only those with serum ferritin testing were included. The following data were collected: tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up.

Results: In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron.

Conclusions: Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

Kanaan AS, Yu D, Metere R, Schäfer A, Schlumm T, Bilgic B, Anwander A, Mathews CA, Scharf JM, Müller-Vahl K, Möller HE. Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome. Neurobiol Dis. 2023 Aug 2;185:106252. doi: 10.1016/j.nbd.2023.106252. Epub ahead of print. PMID: 37536382.


Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.

Tang CY, Wen F. Serum ferritin levels in children with attention deficit hyperactivity disorder and tic disorder. World J Clin Cases. 2022 Aug 6;10(22):7749-7759. doi: 10.12998/wjcc.v10.i22.7749. PMID: 36158507; PMCID: PMC9372851.


Background: Iron plays an important role in neurodevelopmental functions in the brain. Serum ferritin levels are different in children with attention deficit hyperactivity disorder and tic disorder than in healthy children.

Aim: To explore the current status of iron deficiency in children with neurodevelopmental disorders and its sex and age effects.

Methods: A total of 1565 children with attention deficit hyperactivity disorder (ADHD), 1694 children with tic disorder (TD), 93 children with ASD and 1997 healthy control children were included between January 1, 2020, and December 31, 2021 at Beijing Children's Hospital. We describe the differences in age levels and ferritin levels between different disease groups and their sex differences. The differences between the sexes in each disease were analyzed using the t test. The incidence rate of low serum ferritin was used to describe the differences between different diseases and different age groups. A chi-square test was used to analyze the difference in the incidence of low serum ferritin between the disease group and the control group. Analysis of variance was used for comparisons between subgroups, and regression analysis was used for confounding factor control.

Results: A total of 1565 ADHD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 36.82 ± 20.64 μg/L and 35.64 ± 18.56 μg/L, respectively. A total of 1694 TD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 35.72 ± 20.15 μg/L and 34.54 ± 22.12 μg/L, respectively. As age increased, the incidence of low serum ferritin in ADHD and TD first decreased and then increased, and 10 years old was the turning point of rising levels. The incidence of ADHD with low serum ferritin was 8.37%, the incidence of TD with low serum ferritin was 11.04%, and the incidence of the healthy control group with low serum ferritin was 8.61%, among which male children with TD accounted for 9.25% and female children with TD accounted for 11.62%. There was a significant difference among the three groups (P < 0.05). In addition, there were 93 children with ASD with an average serum ferritin level of 30.99 ± 18.11 μg/L and a serum ferritin incidence of 15.05%.

Conclusion: In conclusion, low serum ferritin is not a risk factor for ADHD or TD. The incidence of low serum ferritin levels in children with ADHD and TD between 5 and 12 years old decreases first and then increases with age.

Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, Bai YM. Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study. BMC Psychiatry. 2013 Jun 4;13:161. doi: 10.1186/1471-244X-13-161. PMID: 23735056; PMCID: PMC3680022.


Background: A great deal of evidence has shown that iron is an important component in cognitive, sensorimotor, and social-emotional development and functioning, because the development of central nervous system processes is highly dependent on iron-containing enzymes and proteins. Deficiency of iron in early life may increase the risk of psychiatric morbidity.

Methods: Utilizing the National Health Insurance Database from 1996 to 2008, children and adolescents with a diagnosis of IDA were identified and compared with age and gender-matched controls (1:4) in an investigation of the increased risk of psychiatric disorders.

Results: A total of 2957 patients with IDA, with an increased risk of unipolar depressive disorder (OR = 2.34, 95% CI = 1.58 ~ 3.46), bipolar disorder (OR = 5.78, 95% CI = 2.23 ~ 15.05), anxiety disorder (OR = 2.17, 95% CI = 1.49 ~ 3.16), autism spectrum disorder (OR = 3.08, 95% CI = 1.79 ~ 5.28), attention deficit hyperactivity disorder (OR = 1.67, 95% CI = 1.29 ~ 2.17), tic disorder (OR = 1.70, 95% CI = 1.03 ~ 2.78), developmental delay (OR = 2.45, 95% CI = 2.00 ~ 3.00), and mental retardation (OR = 2.70, 95% CI = 2.00 ~ 3.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (OR = 5.56, 95% CI = 1.98 ~ 15.70) and tic disorder (OR = 2.95, 95% CI = 1.27 ~ 6.86).

Conclusion: Iron deficiency increased the risk of psychiatric disorders, including mood disorders, autism spectrum disorder, attention deficit hyperactivity disorder, and developmental disorders. Further study is required to clarify the mechanism in the association between IDA and psychiatric disorder.

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