Dopamine deficiency refers to low levels of dopamine in the brain which can adversely affect our emotional responses and movements. This can cause dopamine deficiency syndrome, which is a hereditary movement disorder. It is an extremely rare condition.
What Is Dopamine Deficiency?
Dopamine is a neurotransmitter that regulates our motivation, pleasure and reward system. It is also associated with memory, learning and motor system function. According to a 2016 study 1 Juárez Olguín, H., Calderón Guzmán, D., Hernández García, E., & Barragán Mejía, G. (2016). The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxidative medicine and cellular longevity, 2016, 9730467. https://doi.org/10.1155/2016/9730467 , “Dopamine (DA) plays a vital role in reward and movement regulation in the brain.” Researchers from another study 2 Juárez Olguín, H., Calderón Guzmán, D., Hernández García, E., & Barragán Mejía, G. (2016). The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxidative medicine and cellular longevity, 2016, 9730467. https://doi.org/10.1155/2016/9730467 explain “DA plays multiple functions in the brain.”
However, unbalanced or low levels of dopamine can result in various severe mental and physical health conditions. Although we may not be able to accurately measure the dopamine levels in our brain, low levels of DA and irregular DA activity can lead to certain symptoms and ailments, such as Parkinson’s disease, attention deficit hyperactivity (ADHD), schizophrenia, depression and addiction.
Dopamine deficiency may indicate –
- Low production and release of dopamine
- Not enough or insufficient dopamine receptors
- Dopamine receptors are flawed or damaged
- Dopamine is not being effectively recirculated
- Dopamine is not properly broken down
Although dopamine deficiency is not regarded as a separate medical diagnosis, it can cause Dopamine deficiency syndrome, which is a rare medical disorder.
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Dopamine Deficiency Syndrome
One of the primary conditions caused by low DA is the Dopamine deficiency syndrome. This rare movement disorder, also known as a Dopamine transporter deficiency syndrome (DTDS) and Infantile Parkinsonism-Dystonia, has been identified as the first inherited dopamine transportopathy 3 Blackstone C. (2009). Infantile parkinsonism-dystonia: a dopamine “transportopathy”. The Journal of clinical investigation, 119(6), 1455–1458. https://doi.org/10.1172/jci39632 .
“DTDS is a recently described neurotransmitter disease that is classically characterized by an infantile onset, complex progressive motor disorder that is pharmacoresistant and life-limiting,” explains a 2014 study 4 Ng, J., Zhen, J., Meyer, E., Erreger, K., Li, Y., Kakar, N., Ahmad, J., Thiele, H., Kubisch, C., Rider, N. L., Morton, D. H., Strauss, K. A., Puffenberger, E. G., D’Agnano, D., Anikster, Y., Carducci, C., Hyland, K., Rotstein, M., Leuzzi, V., Borck, G., … Kurian, M. A. (2014). Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. Brain : a journal of neurology, 137(Pt 4), 1107–1119. https://doi.org/10.1093/brain/awu022 on DTDS. The condition is known to be progressively worsening, early infantile-onset parkinsonism and dystonia. It is regarded as extremely rare as there have been only 20 confirmed patients of DTDS mentioned in medical literature, according to the U.S. National Library of Medicine. It is believed that this syndrome may be underdiagnosed or misdiagnosed as the symptoms tend to be common with movement disorders, like cerebral palsy. Hence, it is believed that the condition may not be as rare as believed earlier.
DTDS severely affects an individual’s ability to control or move their muscles and body. Generally, symptoms tend to appear in infancy but in some cases they may appear later in life. As of now, there is no specific cure for DTDS. However, treatment focused on managing the symptoms can prove to be helpful.
Understanding DTDS
Dopamine deficiency syndrome usually develops during infancy and worsens progressively over time. However, sometimes the symptoms may become noticeable only in childhood or later. Dopamine transporter deficiency syndrome can cause dystonia, which involves a pattern of sustained, involuntary muscle contractions. The contractions tend to affect a range of different muscles and lead to constant muscle spasms and cramps. This can significantly impair a person’s ability to conduct daily activities, such as walking, eating, drinking and even speaking.
The affected person may eventually develop parkinsonism as the condition becomes worse. Parkinsonism is characterized by different movement abnormalities, such as bradykinesia (abnormally slow movement), rigidity, tremors and postural instability or being unable to balance or hold the body upright. DTDS can adversely affect a person’s lifespan.
However, researchers are yet to identify the long-term effects of this syndrome on the patients. The development of dopamine deficiency syndrome is regarded as a continuum as it involves early-onset DTDS, where the symptoms arise in the first 6 months; and atypical later-onset DTDS, where onset occurs in childhood, adolescence or even adulthood. If the symptoms arise later in life, then it may continue into adulthood.
Symptoms Of Dopamine Deficiency
Some of the most common signs and symptoms associated with DA deficiency, irrespective of the age of onset, include the following:
1. Physical symptoms
Here are some general signs of low DA levels in the brain:
- Bradykinesia (unnaturally slow movement of muscles)
- Muscle stiffness (rigidity)
- Muscle spasms
- Muscle cramps
- Tremors
- Aches & pains
- Loss of balance when standing or walking
- Difficulty holding the body in an upright position
- Difficulty speaking or talking slower than usual
- Unmanageable eye movements
- Difficulty sleeping or disturbed sleep
- Trouble eating or swallowing
- Constipation
- Gastroesophageal reflux disease (GERD)
- Frequent pneumonia
- Weight loss or gain
- Changes in coordination
- Restless leg syndrome
2. Psychological symptoms
Low levels of DA may also cause the following psychological symptoms as well:
- Lack of focus or concentration
- Low energy
- Lack of motivation
- Constant feelings of fatigue
- Low mood or feelings of sadness
- Feeling hopeless
- Frequent mood swings
- Having low self-esteem
- Anxiety
- Feelings of guilt
- Hallucinations
- Delusions
- Lack of self-awareness
- Depression
- Working memory issues
- Inability to feel pleasure
- Symptoms of dementia
- Symptoms of schizophrenia
- Symptoms of attention-deficit hyperactivity (ADHD)
- Self-harm or suicidal tendencies
3. DTDS symptoms
Apart from the common symptoms of dopamine deficiency, here are some specific symptoms 5 Dopamine transporter deficiency syndrome. Genetics Home Reference (GHR). October, 2015; https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome. of Dopamine transporter deficiency syndrome (DTDS):
- Parkinsonism
- Abnormal circulating carboxylic acid concentration
- Abnormal pyramidal sign
- Absent speech
- Bradykinesia
- Cerebral palsy
- Hypokinesia
- Constipation
- Chorea
- Hypomimic face
- Limb hypertonia
- Muscular hypotonia of the trunk
- Oculogyric crisis
- Orofacial dyskinesia
- Feeding difficulties
Causes Of Dopamine Deficiency Syndrome
Low DA levels can be caused by a variety of factors such as serious health conditions or poor lifestyle. Some of the common causes of dopamine deficiency may include –
- Unhealthy & poor diet
- Underlying health conditions
- Lack of protein
- Obesity
- Alcohol withdrawal
- Stress 6 Moriam, S., & Sobhani, M. E. (2013). Epigenetic effect of chronic stress on dopamine signaling and depression. Genetics & epigenetics, 5, 11–16. https://doi.org/10.4137/GEG.S11016
- Drug abuse
However, the dopamine transporter deficiency syndrome (DTDS) is believed to be caused by various factors, some of which are mentioned below:
1. Mutations in the SLC6A3 gene
Researchers believe that DTDS may be caused by the SLC6A3 gene 7 Kurian MA. SLC6A3-Related Dopamine Transporter Deficiency Syndrome. 2017 Jul 27. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK442323/ mutations. This gene promotes the production of the protein known as dopamine transporter (DAT) 8 Torres GE. The dopamine transporter proteome. J Neurochem. 2006 Apr;97 Suppl 1:3-10. doi: 10.1111/j.1471-4159.2006.03719.x. PMID: 16635244. , which is embedded in the membrane of specific neurons or nerve cells in the brain. This helps in transporting DA into the cell which regulates movement control, behavior, motivation and cognition. Mutations in the SLC6A3 gene lead to functional impairments in the DAT. This leads to a deficiency of functional dopamine transporter and affects DA signaling in our brain. According to the 2014 study on DTDS, “Dopamine transporter mutants also showed diminished dopamine binding affinity, reduced cell surface transporter, loss of post-translational dopamine transporter glycosylation and failure of amphetamine-mediated dopamine efflux.”
It is yet to be known how dopamine signaling changes cause certain movement abnormalities seen in individuals with DTDS even though dopamine helps to regulate movement. However, the age of onset is believed to be associated with the intensity of impairment in the function of the dopamine transporter.
2. Autosomal Recessive Inheritance
According to a 2011 study 9 Kurian MA, Li Y, Zhen J, Meyer E, Hai N, Christen HJ, Hoffmann GF, Jardine P, von Moers A, Mordekar SR, O’Callaghan F, Wassmer E, Wraige E, Dietrich C, Lewis T, Hyland K, Heales S Jr, Sanger T, Gissen P, Assmann BE, Reith ME, Maher ER. Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study. Lancet Neurol. 2011 Jan;10(1):54-62. doi: 10.1016/S1474-4422(10)70269-6. Epub 2010 Nov 25. PMID: 21112253; PMCID: PMC3002401. , the inheritance of dopamine deficiency syndrome is autosomal recessive 10 Goldstein, D. Y., & Prystowsky, M. (2017). Autosomal Recessive Inheritance: Cystic Fibrosis. Academic pathology, 4, 2374289517691769. https://doi.org/10.1177/2374289517691769 and is related to impaired dopamine transporter function. The researchers explain “dopamine transporter deficiency syndrome is the first identified parkinsonian disorder caused by genetic alterations of the dopamine transporter.” Autosomal recessive is a pattern in which a disorder is passed down among first-degree family members.
An autosomal recessive pattern indicates that two copies of the gene mutations must be present for the disorder to develop. Each parent of the affected person with the autosomal recessive disease carries one copy of the abnormal gene. However, the parents usually do not show any symptoms of the disorder. According to a 2017 study 11 Yildiz Y, Pektas E, Tokatli A, Haliloglu G. Hereditary Dopamine Transporter Deficiency Syndrome: Challenges in Diagnosis and Treatment. Neuropediatrics. 2017 Feb;48(1):49-52. doi: 10.1055/s-0036-1593372. Epub 2016 Sep 30. PMID: 27690368. , “Hereditary dopamine transporter deficiency syndrome (DTDS) is a neurotransmitter disorder caused by a defect in the neuronal uptake of dopamine.”
Other Conditions Associated With Dopamine Deficiency
Apart from DTDS, low levels of dopamine can also cause a range of other mental and physical health issues. Studies 12 Drozak J, Bryła J. Dopamina–nie tylko neuroprzekaźnik [Dopamine: not just a neurotransmitter]. Postepy Hig Med Dosw (Online). 2005;59:405-20. Polish. PMID: 16106242. show that dopamine deficiency is associated with a number of different psychiatric and neurological disorders, such as Parkinson’s Disease 13 Mishra, A., Singh, S., & Shukla, S. (2018). Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson’s disease. Journal of experimental neuroscience, 12, 1179069518779829. https://doi.org/10.1177/1179069518779829 , Alzheimer’s disease 14 Martorana, A., & Koch, G. (2014). “Is dopamine involved in Alzheimer’s disease?”. Frontiers in aging neuroscience, 6, 252. https://doi.org/10.3389/fnagi.2014.00252 , schizophrenia and drug addiction, such as cocaine and amphetamine. Low DA function is also related to Huntington’s disease and attention deficit hyperactivity (ADHD) 15 Wu J, Xiao H, Sun H, Zou L, Zhu LQ. Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol. 2012 Jun;45(3):605-20. doi: 10.1007/s12035-012-8278-5. Epub 2012 May 19. PMID: 22610946. .
A 2019 study 16 Klein MO, Battagello DS, Cardoso AR, Hauser DN, Bittencourt JC, Correa RG. Dopamine: Functions, Signaling, and Association with Neurological Diseases. Cell Mol Neurobiol. 2019 Jan;39(1):31-59. doi: 10.1007/s10571-018-0632-3. Epub 2018 Nov 16. PMID: 30446950. explains that dopamine signaling pathways are potentially involved “in evoking the onset and progression of some diseases in the nervous system, such as Parkinson’s, Schizophrenia, Huntington’s, Attention Deficit and Hyperactivity Disorder, and Addiction.” Studies 17 Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354-7. doi: 10.1016/s0140-6736(00)03643-6. PMID: 11210998. reveal that dopamine deficiency is also linked with obesity and pathological eating. Researchers 18 Wang GJ, Volkow ND, Fowler JS. The role of dopamine in motivation for food in humans: implications for obesity. Expert Opin Ther Targets. 2002 Oct;6(5):601-9. doi: 10.1517/14728222.6.5.601. PMID: 12387683. believe that “low brain DA activity in obese subjects predisposes them to excessive use of food.”
Low DA levels also increase the risk of a number of mental health disorders schizophrenia, depression and addiction. According to a 2014 study 19 Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H. G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., & Gos, T. (2014). The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Frontiers in psychiatry, 5, 47. https://doi.org/10.3389/fpsyt.2014.00047 found that dopamine abnormalities have been found to be involved in schizophrenia. Research 20 Brown AS, Gershon S. Dopamine and depression. J Neural Transm Gen Sect. 1993;91(2-3):75-109. doi: 10.1007/BF01245227. PMID: 8099801. also shows that DA levels also play a significant role in depression. A 2017 study 21 Belujon, P., & Grace, A. A. (2017). Dopamine System Dysregulation in Major Depressive Disorders. The international journal of neuropsychopharmacology, 20(12), 1036–1046. https://doi.org/10.1093/ijnp/pyx056 in major depressive disorder and anhedonia revealed that “Anhedonia is considered a core feature of major depressive disorder, and the dopamine system plays a pivotal role in the hedonic deficits described in this disorder.” Scientists have also found that dopamine deficiency strongly influences addiction as well. “As a result of habitual intake of addictive drugs, dopamine receptors expressed in the brain are decreased,” explains a recent study.
Diagnosis Of Dopamine Deficiency Syndrome
As there is no accurate way to effectively measure DA levels in our brain, diagnosing dopamine deficiency may be challenging. Moreover, the diagnosis of rare, genetic conditions are often difficult. However, a healthcare professional can utilize certain certain techniques to determine imbalance of DA levels in a person’s brain. A doctor may check the patient’s family and medical history, lifestyle factors, analyze their symptoms and conduct certain lab tests and physical exams to make a diagnosis.
Although dopamine levels can be measured by a blood test, the brain’s response to DA cannot be evaluated. Apart from testing blood samples for the genetic markers of DTDS, doctors may also test cerebrospinal fluid for assessing acids linked to DA. This is called a neurotransmitter profile. Apart from these, the Genetic Testing Registry (GTR) can also offer necessary information about genetic tests for Dopamine transporter deficiency syndrome.
As DA levels can also be influenced by certain underlying medical conditions, doctors often focus on diagnosing a patient based on their symptoms instead of testing DA levels. If you believe that you have dopamine deficiency, then make sure to consult a doctor immediately as the symptoms are manageable, even though there is no specific cure.
Treatment Of Dopamine Deficiency Syndrome
There is no standardized or established treatment plan for DTDS. The doctor needs to work closely with the patient to determine what treatment approach and medications may work through trial and error. According to studies 22 Kurian, M. A., Li, Y., Zhen, J., Meyer, E., Hai, N., Christen, H. J., Hoffmann, G. F., Jardine, P., von Moers, A., Mordekar, S. R., O’Callaghan, F., Wassmer, E., Wraige, E., Dietrich, C., Lewis, T., Hyland, K., Heales, S., Jr, Sanger, T., Gissen, P., Assmann, B. E., … Maher, E. R. (2011). Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study. The Lancet. Neurology, 10(1), 54–62. https://doi.org/10.1016/S1474-4422(10)70269-6 , other movement disorders, such as Parkinson’s disease, which are also related to dopamine production, can be effectively treated with levodopa (L-Dopa) 23 Gandhi KR, Saadabadi A. Levodopa (L-Dopa) [Updated 2020 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482140/ , the precursor to dopamine, to relieve symptoms. Researchers have used the dopamine antagonists pramipexole 24 Singh R, Parmar M. Pramipexole. [Updated 2020 Dec 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557539/ and ropinirole 25 Rewane A, Nagalli S. Ropinirole. [Updated 2020 Jul 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554532/ to treat dopamine deficiency syndrome as these medications help to relieve symptoms of Parkinson’s disease in adults. Although there has been some success, further research is necessary to understand the long-term and short-term side effects.
Apart from medications, counseling and physical therapy to improve movement difficulties and muscle stiffness can be effective as well. Moreover, certain lifestyle and diet changes can also help to improve dopamine in the body and relieve the symptoms. Some helpful strategies may include:
- Eating protein-rich foods, like fish, meat, eggs, dairy, soy, legumes, nuts and seeds, as the amino acid tyrosine 26 Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr. 2007 Jun;137(6 Suppl 1):1539S-1547S; discussion 1548S. doi: 10.1093/jn/137.6.1539S. PMID: 17513421. helps to boost DA levels.
- Avoiding consuming foods that are high in saturated fat and sugar.
- Getting enough sleep as undisturbed sleep 27 Korshunov, K. S., Blakemore, L. J., & Trombley, P. Q. (2017). Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System. Frontiers in cellular neuroscience, 11, 91. https://doi.org/10.3389/fncel.2017.00091 helps to produce DA.
- Engaging in exercise 28 Lin, T. W., & Kuo, Y. M. (2013). Exercise benefits brain function: the monoamine connection. Brain sciences, 3(1), 39–53. https://doi.org/10.3390/brainsci3010039 and physical activity on a regular basis.
- Practicing relaxation techniques like meditation 29 Krishnakumar, D., Hamblin, M. R., & Lakshmanan, S. (2015). Meditation and Yoga can Modulate Brain Mechanisms that affect Behavior and Anxiety-A Modern Scientific Perspective. Ancient science, 2(1), 13–19. https://doi.org/10.14259/as.v2i1.171 to avoid stress.
- Consuming probiotics 30 Sarkar, A., Lehto, S. M., Harty, S., Dinan, T. G., Cryan, J. F., & Burnet, P. (2016). Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals. Trends in neurosciences, 39(11), 763–781. https://doi.org/10.1016/j.tins.2016.09.002 to promote DA production.
- Listening to instrumental music 31 Ferreri L, Mas-Herrero E, Zatorre RJ, Ripollés P, Gomez-Andres A, Alicart H, Olivé G, Marco-Pallarés J, Antonijoan RM, Valle M, Riba J, Rodriguez-Fornells A. Dopamine modulates the reward experiences elicited by music. Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3793-3798. doi: 10.1073/pnas.1811878116. Epub 2019 Jan 22. PMID: 30670642; PMCID: PMC6397525. to promote dopamine release in the brain.
- Taking vitamin 32 Guilarte TR. Effect of vitamin B-6 nutrition on the levels of dopamine, dopamine metabolites, dopa decarboxylase activity, tyrosine, and GABA in the developing rat corpus striatum. Neurochem Res. 1989 Jun;14(6):571-8. doi: 10.1007/BF00964920. PMID: 2761676. and mineral supplements.
However, it should be noted that there is no conclusive evidence that altering diet or using home remedies can help to treat dopamine deficiency syndrome.
Overcoming Dopamine Deficiency
Dopamine deficiency can cause a wide range of physical and psychiatric health problems, including Dopamine transporter deficiency syndrome (DTDS). As evidence is limited regarding the effectiveness of diet changes and home remedies, one of the best ways to overcome dopamine deficiency is to seek medical attention immediately. If you think you or a loved one is suffering from low DA levels, then make sure to consult a doctor and follow the treatment plan strictly. With the help of medications and physiotherapy, one can relieve DTDS symptoms in the long run.
