Many parents of twitching children ask me why their children are twitching. So far the causes of twitching in children may be the following.
I. Genetic factors
The first case of TD was discovered in 1825, and the earliest paper on TD published in 1885 mentioned that the disease was characterized by family aggregation. In more than a century of research in the following years, there were many data confirming the familial nature of TD. In the last decade of these studies, the literature dealing with the family lineage of TD has used structured retrospective studies to collect information on the prevalent individuals and their families, and all studies have also used the most advanced diagnostic tools and methods of the time to examine the prevalent individuals and their families, with extremely similar results, with the prevalence of TD among relatives ranging from 9.8% to 15%, while the rate of tic disorders ranges from 15% to 20%, and these These data are significantly higher than the prevalence of tic disorders in the general population/control group. Among them, Huang Yi et al. conducted a study on 171 families with tic disorders and found not only that the prevalence of TD and tic disorders was significantly higher among first- and second-degree relatives of people with TD, suggesting a clear familial aggregation of TD, but also that the clinical manifestations of tic disorders transmitted by the paternal line differed from those transmitted by the maternal line. The genetic susceptibility to TD is reflected in twin studies. A study of 16 monozygotic twin pairs in which one of the twins had polydactyly found that the concordance (the presence of a particular identical genetic trait in a pair of twins) for TD was 56%, and up to 94% when any tic disorder was included.
Half of the patients’ inheritance patterns were associated with a master gene effect. In contrast to previous studies, the survey of 108 families did not find any basis for suggesting a Mendelian inheritance pattern for TD, and it is noteworthy that the risk rate for TD reassortment in these families was similar to other studies. Therefore, it is difficult to figure out why the results of so many segregation studies are inconsistent. Nonetheless, most studies have concluded that there is much evidence in the genetic background of TD for an important role of the master gene in the TD phenotype.
II. Neurotransmitter imbalance
1. Monoamine transmitters
Through in vivo and in vitro scientific studies, no specific alterations of pathological dissection were found in the brains of TD patients. Coupled with the discovery that haloperidol, a dopamine D2 receptor (DRD2) antagonist, was effective in reducing tic symptoms since the 1960s, the relationship between neurotransmitters and TD began to be noticed and a lot of research was conducted. Most scholars now believe that abnormalities of various central neurotransmitters play an important role in the pathogenesis of this disease, mainly related to abnormalities of monoamine neurotransmitters such as dopamine, 5-monohydroxytryptamine and norepinephrine, with the closest relationship between dopamine (DA) and TD. The clinical use of central dopaminergic receptor blockers can improve the clinical symptoms of TD, while dopaminergic agonists can aggravate the symptoms of patients, and the application of central dopaminergic receptor blockers can lead to delayed twitching symptoms as well as a decrease in the DA metabolite hypericum (HAV) in the cerebrospinal fluid of TD patients, and the degree of decrease correlates with the severity of symptoms, suggesting that the abnormalities of central dopaminergic receptors and transmitters are involved in the pathogenesis of TD. Current research on the neurobiochemical mechanisms of TD has focused on the DA system, especially dopamine receptor hypersensitivity and dopaminergic hyperinnervation.
2. Dopaminergic nerve fiber hyperinhibition
The nigrostriatal pathway is an important component of the extrapyramidal system, which is the basic structure regulating all behavioral responses. The imbalance of DA channel balance in the midbrain and midbrain limb leads to the impaired inhibition of the limbic system, which is the neurobiochemical basis of TD. The substantia nigra-striatal pathway is the most important structure for mobilizing all behavioral movements. Animal experiments have shown that excessive dopamine projections to the striatum will lead to excessive and rapid responses in the cortical-striatal-pallidum-thalamocortical loop, resulting in spontaneous hyperactivity, so that dopaminergic hyperinnervation in the striatum plays a pathogenic role in loop homeostasis. The dopamine and its final metabolite and intermediate metabolite dihydroxyphenylacetic acid were normal in brain tissue, so it is believed that striatal dopaminergic hyperinnervation is the causative agent of TD. Dopamine transporter protein (DAT) is a membrane protein present in the presynaptic membrane of central dopaminergic neurons and is a good indicator of the activity of dopaminergic-containing nerve end sites. Altered striatal DAT activity parallels the physiological and pathological functional changes in nigrostriatal dopaminergic neurons.
3.Dopamine receptor hypersensitivity
Dopamine receptor hypersensitivity is defined as an increase in the number or affinity of postsynaptic dopamine receptors.The basal ganglia striatal dopamine receptor hypersensitivity in TD was discovered in the study of hypericin. Homovanillic acid is a metabolic end product of dopamine and reflects the dynamics of dopamine in the brain. homovanillic acid, the main metabolite of dopamine, is significantly lower in the plasma and cerebrospinal fluid of children with TD compared to normal controls, and the degree of reduction correlates significantly with the severity of symptoms. increased levels of homovanillic acid after treatment with haloperidol, which is considered dopaminergic postsynaptic receptor hypersensitivity, inhibits the release of presynaptic dopamine through a negative feedback mechanism Pre-synaptic dopamine release, the number of dopamine in the inter-synaptic transport increased, so that the clearance of dopamine increased, so the HAV was lower than normal before treatment, and after treatment the postsynaptic dopamine receptors were blocked by the drug post-synaptic neurons feedback excitation, presynaptic neurons released more dopamine, and thus the corresponding metabolites increased.
4. Amino acid transmitters
It has been claimed that children with TD have a genetic defect that will affect the developmental processes of the basal ganglia and limbic system associated with reproductive behavior and promoting basic movement, vocalization, and emotion. Under the influence of sex hormones and mediated by excitatory amino acids, this leads to an inappropriate increase in the number of neurons and excessive derivation of neuronal synapses due to excessive trophic effects during early brain development, resulting in clinical manifestations of involuntary twitching. It has also been suggested that the “excitotoxic effect” of excitatory amino acids during brain development can cause continuous depolarization of excitatory neurons, resulting in intracellular calcium overload, which may also be related to the development of TD. For example, excitatory amino acids such as glutamate (MSG) levels in the brain of children with TD are significantly increased, and blood glutamate levels may return to normal as symptoms decrease. The main component of MSG, a commonly used food flavoring agent, is glutamic acid, which has been reported to damage the central nervous system of newborn animals. Controlling the consumption of diet containing more additives can effectively control TD symptoms.
Immunity and infection factors
In recent years, the study of neuro-endocrine immune network theory has been intensified, and the immune etiology of TD and its related neuropsychiatric diseases such as OCD, attention deficit hyperactivity disorder and schizophrenia has gradually come to the attention of scholars, but the study is still immature, mainly focusing on the study of streptococcal infection and its pathogenesis correlation.
Some studies have also reported that TD is associated with viral infections, and the theory of viral infection in TD is gradually gaining attention. The theory of viral infection is also supported by viral encephalitis, hepatitis and upper respiratory tract infections that induce or aggravate the disease. When the infection is controlled, the twitching stops and the improvement of hyperactivity and behavioral problems is obvious.
The occurrence of TD due to mycoplasma infection has been reported in recent years. Whether it is the sense of other pathogens has not been determined, but mycoplasma infection should be considered at least as an aggravating factor for TD.
IV. Psychiatric factors
Early studies considered TD to be a manifestation of repressed personal desires and rebellious psychology, and some children may suddenly develop tic symptoms when they encounter life events that hurt their feelings, and tic symptoms may worsen in almost all children with mental stress, and some tic symptoms may be relieved with psychotherapy, thus emphasizing the role of mental factors in the development of TD. Family structure has an impact on children’s psychological development and personality formation.
Children are in a relatively poor family environment, and special attention should be paid to the improvement of the family environment in the treatment of tic disorders. Investigations in recent years have found that TD is related to overly strict family education. The current family structure in China is dominated by only children, and in the early education process, parents are too strict and harsh to children, and after going to school, they add too much study burden to children and restrict their activities too much, parents have too high expectations of their children, plus schools are too strict to students, which makes children live in a tense and fearful environment, and they can’t relax emotionally and get warmth, resulting in the difference between external pressure and The deviation of the child’s psychological capacity may lead to the onset of the disease, and this deviation from the normal regulatory education is believed to be one of the causative factors of TD. Scolding and corporal punishment can further aggravate the symptoms of the disease.
Developmental pediatrics particularly emphasizes the close association between the quality of the mother-child relationship and the onset of the disease, such as maternal overprotection, high expectations, excessive interference, neuroticism, and reprimanding at every turn, which are particularly likely to trigger or exacerbate the child’s tic symptoms. Therefore, in addition to medication, we should also focus on psychological intervention of the child, suggesting that parents should care for their children rationally, ignore frequent twitching, and turn a blind eye to the child’s condition.
V. Allergic factors
Some researchers believe that the symptoms of TD patients are related to allergic reactions. 300 patients with TD were examined in 1984, and although there is no evidence that allergic reactions are the cause of the disease, it can be observed clinically that the deterioration of TD is often related to seasonal allergic reactions, the intake of allergens in food and the use of drugs for the treatment of allergic reactions.