They are due to an urge or sensation that eases after performing the movement or the sound.

1. What Are the Types of Tics?

1.1. Primary Tics

• Transient tic disorder

Transient tic disorders are motor or vocal tics that last for less than a year.

• Chronic tic disorder

Chronic tic disorders are motor or vocal tics that last for more than a year.

• Adult-onset tic disorder

Adult-onset tic disorder is a recurrent childhood tic disorder; however, this subtype can be classified as a secondary tic disorder if it is due to acquired conditions such as encephalitis or head trauma [2].

• Tourette syndrome

Tourette syndrome is a neurological disease that affects certain parts of the brain (frontal subcortical circuits) responsible for voluntary movements [3].

It is characterized by both vocal and motor chronic tics that are sudden and repetitive such as blinking, clearing throat, grunting, or facial movements [4].

The genetic causes of Tourette’s Syndrome are unknown; however, some cases are associated with mutations in genes such as SLITRK1, CNTNAP2, and HDC.

SLITRK1 is a protein found in the membrane of neurons where it is involved in the regulation of synapses.

CNTNAP2 is a protein found in the membrane of the neurons where it plays a role in axons, while HDC is an enzyme involved in the function of the neurotransmitter histidine.

1.2. Secondary Tics

Secondary tics can be associated with the following disorders and conditions:

• Global Brain Developmental Disorder

This disorder is due to neurodevelopmental anomalies that lead to delays in the development of social and communication skills, such as autism, mental retardation (intellectual disability), and Pervasive developmental disorders (PDD).

• Infections

Examples of infections that affect the nervous system such as:

Viral Encephalitis

It is an inflammation of the brain caused by a viral infection.

Creutzfeldt–Jakob Disease

Creutzfeldt-Jacob disease is a progressive neurodegenerative disease affecting the brain and causing cognitive disorders such as memory loss, changes in behavior, and ataxia (uncoordinated movements)

The disease is due to the accumulation of a glycoprotein known as a prion, which functions in the brain are not well known [5].

Post-Streptococcal Disorders

Post-streptococcal disorders are autoimmune disorders that happen following infections with a type of bacteria known as Staphylococcus pyogenes.

• Genetic and Neurodegenerative Diseases

Wilson Disease

Wilson disease is a rare genetic disease characterized by the accumulation of copper in different parts of the body including the brain [6].

Huntington Disease

Huntington’s Disease is a neurodegenerative disease that affects the brain causing dementia, depression, difficulty focusing, involuntary movement, stumbling, and clumsiness  [7].

Neuroacanthocytosis

Neuroacanthocytosis is a group of genetic disorders characterized by anomalies of red blood cells (acanthocytosis) and movement disorders [8].

Hallervorden-Spatz Syndrome

Hallervorden-Spatz syndrome is a rare neurodegenerative disease characterized by the accumulation of iron in a part of the brain known as basal ganglia causing its damage [9].

• Drugs

Drugs such as caffeine [10], carbamazepine [11], cocaine [12], and lamotrigine [13].

• Toxins

Carbon monoxide poisoning [14].

• Brain injury

Head trauma [15], stroke (very low supply of oxygen to the brain), and ischemic encephalopathy (low supply of oxygen to the brain) [16].

• Immune Disorders of the Central Nervous System (CNS)

Antiphospholipid Antibody Syndrome

This syndrome is characterized by the production of antibodies against phospholipids in the body which increases the risk of blood clots and thrombosis [17].

Sydenham’s Chorea

Sydenham’s Chorea is a neurological disorder that affects children after an infection with a group A beta-hemolytic streptococcus (GABHS) [18].

• Psychiatric Disorders

Schizophrenia

Schizophrenia is a complex and severe mental health disorder that is classified as a type of psychosis. It is characterized by significant alterations in thoughts, perception, mood, and behaviors [19].

Psychogenic tics

Psychogenic tics are characterized by the sudden onset of brief motor tics that are due to an urge or sensation that can be suppressed. Psychogenic tics can be due to the body’s response to stress [20].

2. What Are the First Signs of Tics?

The initial evaluation of tics is difficult as other disorders may have similar signs such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), dyskinesis, stereotypies, or tourettism [21].

3. Do Tic Disorders Go Away?

An improvement in individuals affected by tics is generally observed by adolescence or early adulthood; therefore, waiting for a period of time can lessen the severity of the tics.

4. How Are Tics Treated?

Most individuals with tics do not seek treatment and education of the affected individual, family, and school environment (e.g., school personnel) about the causes of tics is the initial intervention [21].

This educational approach can prevent such as embarrassment, bullying, anger, self-harm, and social isolation.

However, if the tics become severe, non-pharmacological and pharmacological tic-suppressive medications are provided [21] [22].

• Non-pharmacological treatment

Behavioral Therapy

The aim of this therapy is to help the affected individuals to manage their tics and reduce their severity.

Habit Reversal

This intervention involves awareness training and competing response training.

The awareness training request from the affected individual to name the tic loud, while in the competing response training, the affected individual learns to do a new behavior every time the tic manifests [22].

• Pharmacological treatment

Although most prescribed medications for tics are not approved by the US FDA (Food and Drug Administration), Tics-suppressing medications such as alpha-2-agonists, dopamine blocking agents, are used for severe cases of tics to help individuals with tics with their daily life  [21].

Conclusion

Tic disorders can be primarily associated with Tourette’s syndrome but can also be related to physical and mental disorders, brain injury, drugs, or intoxications. Fortunately, an improvement in individuals affected by tics is generally observed by adolescence or early adulthood. Meanwhile, some of the affected individuals may suffer from embarrassment, bullying, and isolation, due to a lack of education on the causes of tics.

Therefore, is essential that the affected individual learn how to manage the tics in everyday life to reduce associated discomfort, stress, and anxiety.

The education of the family and people in close contact with the affected individual can also significantly reduce embarrassment and bullying through better understanding the difficulties facing an individual with a tic disorder.

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• Acetylcholine
• Dopamine
• Glutamate
• GABA
• Serotonin
• Norepinephrine
• Histamine

Neurotransmitters are produced by neurons and released in gaps that are found between neurons and between neurons and organs. These junctions are known as synapses.

When neurotransmitters are released in the synapses by a neuron, they go and bind to receptors on the receiving neuron or organ. It is like crossing from one side of a river to the other side.

This transition of neurotransmitters from one side to the other is known as neurotransmission.

As neurotransmitters are chemical messengers, they hold instructions such as excitatory (Doing) or inhibitory (Stop doing) information that is communicated and conveyed between neurons until they reach the target tissue or organ responsible for the execution of a specific action such as thinking, learning, emotions, memory, and movement.

I. What Is Acetylcholine?

Acetylcholine is an organic chemical involved in the transmission of instructions between neurons and muscles known as neuromotor or neuromuscular transmission, and between neurons that transmit information for brain organs and glands that are involved in attention, wakefulness, learning, memory (short-term memory), motivation, and mood and emotion [1].

1- What Is the Role of Acetylcholine in Disorders and diseases?

• Acetylcholine and Myasthenia Gravis

In Myasthenia Gravis, the body produces antibodies against acetylcholine receptors blocking the neuromuscular transmission resulting in muscles weakness and fatigue [2].

• Acetylcholine and Alzheimer’s Disease

As acetylcholine is essential for processing memory and learning, the loss of cholinergic neurons (neurons that uses acetylcholine for neurotransmission) contributes to the causes of Alzheimer’s Disease [3].

2- What Drugs Affect Acetylcholine?

There are drugs that promote the function of acetylcholine (agonists) such as nicotine, muscarine, and neostigmine, while others block its activity (antagonists) such as curare, atropine, scopolamine, and botulinum toxin.

In clinics, myorelaxants are used for the treatment of Myasthenia Gravis using inhibitors of cholinesterase, an enzyme that blocks the function of acetylcholine. For Alzheimer’s Disease, the cholinesterase inhibitor, rivastigmine, is used.

II. What Is Dopamine?

Dopamine is an organic chemical involved in the transmission of instructions between neurons to control movement and reward-motivated behavior, such as pleasure, craving, decision making based on rewards, associative learning (learning new things), and short-term memory [4].

1- What Is the Role of Dopamine in Diseases and disorders?

• Dopamine and Parkinson’s disease

Parkinson’s disease is due to the loss of neurons that secrete dopamine (substantia Negra region in the brain) and that control movement. As a result, symptoms such as trembling, stiffness, and slower movement are associated with this disease [5].

• Dopamine and Attention Deficit Hyperactivity Disorder (ADHD)

This disorder is associated with defects in dopamine neurotransmission resulting in reduced attention, short-term memory, and impulse control [6].

• Dopamine and Schizophrenia

Although the mechanism is not well known, the excessive use of dopamine stimulants, such as amphetamine, has been shown to induce schizophrenia [7].

2- What Drugs Affect Dopamine?

There are drugs that directly promote the function of dopamine (agonists) such as Deprenyl, while others directly block its activity (antagonists) such as chlorpromazine.

III. What is Glutamate?

Glutamate is the most abundant chemical messenger that is involved in excitatory neurotransmission which increases nerves impulses (action potential). It is implicated in cognitive activity, including memory and learning, the growth of neurons, and the formation of synapses [8].

1- What Is the Role of Glutamate in Diseases and disorders?

• Glutamate and Epileptic Seizures

Due to the high excitatory activity of glutamate (excitotoxicity), neurons are excessively stimulated resulting in uncontrolled shaking and loss of consciousness. If lasting for longer periods these epileptic seizures can lead to brain damage [9].

• Glutamate and Autism (Autism Syndrome Disorder)

This has been associated with alterations in glutamate function during the neurodevelopment of the embryo [10]. The born child has social and communication difficulties as well as limited and repetitive behavior.

• Glutamate and Stroke

Too much glutamate known as excitotoxicity can lead to the destruction of neurons resulting in stroke and death [11].

• Glutamate and Intellectual Disability

This has also been associated with alterations in glutamate function during the neurodevelopment of the embryo [12].

• Glutamate and Amyotrophic Lateral Disability (ALS)

ALS is a progressive degenerative disorder characterized by the loss of motor neurons (movement control) due to glutamate excitotoxicity [8].

• Glutamate and Alzheimer’s Disease

Glutamate excitotoxicity has been associated with the death of neurons, involved in learning and memory, and that is found in the cortex and hippocampus [13].

2- What Drugs Affect Glutamate?

There are drugs that promote the function of glutamate (agonists) such as NMDA (N-methyl-d-aspartate and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), while others block its activity (antagonists) such as ketamine and AP5 ((2R)-amino-5-phosphonovaleric acid).

IV. What is GABA?

GABA (Gamma-Aminobutyric acid) is a chemical messenger and the major inhibitor of neurotransmission by reducing nerves’ impulses (action potential). Therefore, it has an opposite action to that of glutamate, and therefore, ensures balanced neurotransmission. GABA is involved in self-control, emotions, and attention [14].

1- What Is the Role of GABA in disorders?

• GABA and Epileptic seizures

As GABA is an inhibitor of neurotransmission, the reduction in its level in neurons results in excitotoxicity as neurons are excessively stimulated resulting in uncontrolled shaking and loss of consciousness [15].  

• GABA and Sleep Disorder

GABA is known to favor sleep and alterations in its level in neurons will keep them stimulated which affects sleep [16].

• GABA and Anxiety Disorders

GABA has been shown to prevent the activation of the hypothalamus-pituitary gland-adrenal glands axis (HPA axis) that is involved in fear and anxiety. Reduction in the level of GABA promotes anxiety [17].

• GABA and Schizophrenia

Although the mechanism by which GABA is involved in schizophrenia is not well known, it is suggested that the reduction in GABA affects the function of the prefrontal cortex responsible for cognitive control (information processing and behavior) [18].

• GABA and Major Depression

The mechanism linking GABA and major depression is suggested to be like the one involved in anxiety disorders where a deficit in GABA increases the activation of the HPA axis [19].

• GABA and Autism (Autism Syndrome Disorder)

The link between GABA and autism may be due to defect in GABA function during the neurodevelopment of the embryo [20].

2- What Drugs Affect GABA?

There are drugs that promote the function of GABA (agonists) such as muscimol, while others block its activity (antagonists) such as bicuculine and tiagabine.

V. What is Serotonin?

Serotonin is a chemical messenger involved in the neurotransmission of information related to mood, reward, learning, memory, and cognition.

1- What Is the Role of Serotonin in disorders?

• Serotonin and Major depression

Although significant abnormalities in the function of serotonin were seen in depressed patients, the mechanism by which serotonin is involved in depression is not well known [21].

• Serotonin and Autism (Autism Syndrome Disorder)

The link between serotonin and autism may be due to alterations in serotonin function during the neurodevelopment of the embryo [22].

2- What Drugs Affect Serotonin?

There are drugs that directly promote the function of serotonin (agonists) such as lysergic acid diethylamide, fenfluramine, and MDMA (methylenedioxymethamphetamine), while others directly block its activity (antagonists) such as SSRI, ondansetron, and PCPA.

VI.  What is Norepinephrine?

Norepinephrine is a hormone and chemical messenger associated with the “fight-or-flight” response mediated by the HPA axis.

In temporary stressful situations, the hypothalamus secretes CRH (corticotropin-releasing hormone) to stimulate the secretion of ACTH (Adrenocorticotropic hormone) by the pituitary gland leading to the secretion of the hormone noradrenaline (norepinephrine) which instructs the brain and body for action [23].  

1- What Is the Role of Norepinephrine in disorders?

• Norepinephrine and Pheochromocytoma

Pheochromocytoma is a tumor found in the adrenal medulla where norepinephrine is produced. Because tumor cells produce large quantities of norepinephrine, symptoms such as hypertension as observed [24].

• Norepinephrine and Attention Deficit Hyperactivity Disorder (ADHD)

Although the mechanism between norepinephrine and ADHD is not well known, alterations in the processing of norepinephrine appear to be involved in impulsiveness and hyperactivity seen in ADHD [25].

2- What Drugs Affect Norepinephrine?

There are drugs that directly promote the function of epinephrine (agonists) such as moclobemide, idazoxan while others directly block its activity (antagonists) such as fusaric acid.

VII. What is Histamine?

Histamine is a well know actor in local immune responses, and is produced by mast cells and basophils; however, it is also an important neurotransmitter involved in itching following inflammation, and in the regulation of sleep-wakefulness cycle [26].

1- What Is the Role of Histamine in disorders?

• Histamine and Chronic Inflammation Diseases

Histamine is involved in the regulation of the function of immune cells which secrete cytokines that are involved in inflammation. Therefore, alteration of histamine levels is seen in several diseases, including atopic dermatitis, allergic asthma, and allergic rhinitis.

• Histamine and Allergies

Histamine is actively secreted by mast cells and basophils following their activation by allergens (substances causing allergies) which results in swelling, smooth muscle contraction, itching, and tachycardia.

• Mastocytosis

An excess of histamine is produced during mastocytosis which is characterized by increased proliferation of mast cells

2- What Drugs Affect Histamine?

There are drugs that directly block the function of histamine (agonists) such as diphenhydramine (Benadryl).

Conclusion

Neurotransmitters are essential for the function of the nervous system as they transmit information from the brain to other parts of the body and the other way around. Therefore, any alterations in their function have significant impacts on mental health and diseases.

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