Experts believe that dysfunction of dopaminergic system signaling and transportation may cause Parkinson’s, Huntington’s, Tourette Syndrome, schizophrenia, autism, ADHD, and major depression.
This story does not include health advice. It is for information, inspiration, and awareness purposes.
The body tightly regulates all biochemicals (enzymes, lipids, glucose, hormones, neurotransmitters) using complex processes, which we still learn by observing and experimenting in labs and clinics. Due to personal and professional interests, I have studied neurotransmitters for a long time. The most interesting one is dopamine. I introduced it in detail in 2022.
Recently, I wrote about one of the dysregulation factors of another neurotransmitter, serotonin, manifesting as serotonin syndrome (toxicity). This eye-opening story surprised some readers and caught them off guard as they did not know they had been living with those symptoms when taking SSRIs and multiple pain-killing medications.
Similarly, some regular readers also live with symptoms of dopamine dysregulation, and some are under Dopamine Replacement Therapy, showing the symptoms of Dopamine Dysregulation Syndrome or Dopamine Transporter Deficiency Syndrome.
Some people mentioned having symptoms like dizziness, hallucinations, confusion, anhedonia, dyskinesia, and excessive urges for sex, watching porn, shopping, gambling, drug use, social media, or computer games.
Therefore, I decided to write this important story to answer their questions and bridge the gap by distilling my decades of research. Please note that this story is not about scaring my readers. As my spiritual mentor, Marie Curie, convinced me, “There is nothing to be feared in life but only things to be understood.”
What is the real problem with dopamine today?
Dopamine is a highly popular, misunderstood, and misused neurotransmitter. Although there are regulations around the use of dopamine-related medications, some supplements and even illicit or legal drugs are publicly available, misused, or abused, causing public health issues.
Nicotine from tobacco smoking is a prime example of causing addiction to millions of people and causing significant morbidity and mortality globally. Prescribed medications like amphetamines, antipsychotics, and antidepressants target the dopamine system.
Similar to nicotine, recreational drugs like cocaine and methamphetamine can spike dopamine release in the brain’s reward pathways, resulting in increased energy and feelings of euphoria.
You may wonder what is wrong with energy and euphoria, which are wonderful things for a happy and healthy life. Yes indeed. There is nothing wrong with them.
But when they are created artificially, the brain knows it through its punishment pathways which I discussed before in a story titled The Neurobiology of Punishment and Pleasure Regulation in the Brain which you can find a Google search.
From my reviews, observations, and experiences, apart from side effects related to dysregulation, the biggest problem with dopamine mismanagement is addiction/dependence, affecting mental health as a major cause directly or indirectly. As I pointed out before, Depression Has More to Do with Addictions and Less with Economic Conditions.
How does dopamine misuse or mismanagement cause addiction?
Dopamine mismanagement or misuse through unnatural ways can contribute to addiction by disrupting the brain’s reward circuitry, promoting neuroplastic changes, driving cravings, causing withdrawal symptoms, impairing cognitive control, disrupting decision-making, and forming associative memories.
All these mechanisms can impact our mental health in different ways and intensities. Therefore, addressing dopamine dysregulation is crucial for effectively managing addiction, influencing treatment outcomes, and promoting long-term recovery.
I came across various theories and hypotheses explaining addiction from different angles. I list some popular and well-documented ones below and link to peer-reviewed papers for those interested in details.
Deficiency Syndrome, Incentive Sensitization, Dopamine Imbalance, the Allostatic Model of Addiction, involvement of the Mesolimbic Dopamine Pathway, and Food Cue-Reactivity and Craving.
While researching these theories, I came across a concept called ΔFosB, which is related to the theory of Reward Deficiency Syndrome and the Allostatic Model of Addiction, as it plays a role in neuroplasticity and the long-term changes observed in the brain’s reward circuitry due to chronic exposure to addictive behavior such as drug abuse.
What is DeltaFosB?
ΔFosB (DeltaFosB) plays a crucial role in the neurobiological mechanisms underlying addiction. As I discussed and explained ΔFosB in detail before, I will not repeat them here. The title of my article is What DeltaFosB Is and Why It Matters in Solving Addiction Problems.
For those unfamiliar, in a nutshell, ΔFosB is a protein that accumulates in the brain’s reward circuitry in response to chronic exposure to addictive substances.
We can visualize ΔFosB as a conceptual switch for the brain. The dopamine system uses this switch to determine rewards and punishments, keeping a record of the dopamine levels. It acts at the genetic level.
The growing presence of ΔFosB leads to long-lasting changes in gene expression, particularly in regions associated with reward, motivation, and memory.
All stimulants give dopamine hits. The brain keeps the records using ΔFosB by increasing them with each impact. The constant release of dopamine desensitizes the neurons, so the brain needs more dopamine-producing stimulants, like drugs or other substances, to achieve the same effect.
These changes contribute to the development and persistence of addictive behaviors by altering the brain’s sensitivity to rewards and increasing the craving for drugs or other addictive stimuli like sex, gambling, gaming, or shopping.
What is dopamine replacement therapy?
Dopamine replacement therapy (DRT) is a treatment approach primarily used for Parkinson’s disease, a neurodegenerative disorder characterized by the loss of dopamine-producing cells in the brain.
Dopamine replacement therapy aims to improve motor function and quality of life in individuals with Parkinson’s disease. DRT involves administering medications that either directly replace dopamine or enhance dopamine function in the brain.
The most commonly prescribed medications for DRT are levodopa, which is converted into dopamine in the brain, and dopamine agonists, which mimic the action of dopamine on nerve cells.
These medications help alleviate the motor symptoms of Parkinson’s disease, such as tremors, rigidity, and bradykinesia, by replenishing dopamine levels or stimulating dopamine receptors.
Side effects of DRT can vary. Common side effects may include nausea, vomiting, dizziness, low blood pressure (hypotension), irregular heartbeat (arrhythmias), hallucinations, confusion, and dyskinesias (abnormal involuntary movements).
What is Dopamine Dysregulation Syndrome in simple terms?
Dopamine dysregulation syndrome (DDS) is a recently described iatrogenic disturbance that may complicate long-term symptomatic therapy of Parkinson’s disease.
Iatrogenic disorders are the result of diagnostic and therapeutic procedures undertaken on a patient. With the number of drugs prescribed to a single patient, adverse drug reactions are bound to occur. Physicians should take suitable steps to detect and manage them.
In simple terms, iatrogenic disturbance can encompass unintended side effects, complications, or injuries caused by medical procedures, medications, or therapies. The term is commonly used to describe harm or illness due to medical care rather than the underlying condition being treated.
For example, patients with DDS develop an addictive pattern of dopamine replacement therapy use, administering doses over those required to control their motor symptoms.
This is a disorder characterized by compulsive behaviors, such as gambling, shopping, or hypersexuality, that can occur as a side effect of dopamine replacement therapy in patients with Parkinson’s disease.
As mentioned in this paper, knowledge of the reasons why gambling behavior is more widespread in Parkinsonian men than in Parkinsonian women is lacking.
As there are many papers on DDS, I want to summarize a research paper published on the Journal of Neurology, Neurosurgery, and Pschiatry in 2017.
These researchers reviewed 390 articles, identifying 98 cases of DDS. Early-onset Parkinson’s disease (67%) and male gender (83%) were common. DDS presented with significant physical and social impairment, actions to enable or prevent detection of overuse, as well as mood, anxiety, and motor fluctuations.
Past substance and psychiatric history was present in 15.3% and 10.2% of cases. Comorbid impulse control disorders (61%), psychosis (32%), and panic attacks (14%) were common. Various management strategies were used; only 56% of cases were resolved. Sodium valproate was successful in 5/5 cases. The response to deep brain stimulation varied.
Levodopa is still considered the most potent trigger for DDS in Parkinson’s disease, but subcutaneous apomorphine and oral dopamine agonists may also be responsible. In managing DDS, further research is needed to identify at-risk groups, facilitating more effective early intervention.
They concluded that given the functional impairment, medical and psychiatric consequences, and the difficulties of treatment, early identification of DDS should be a priority.
What is Dopamine Transporter Deficiency Syndrome, and how common is it?
As documented in a 2023 paper in MDPI, Dopamine Transporter Deficiency Syndrome (DTDS) is a rare disorder caused by faulty dopamine reuptake in the brain. I will outline the key points.
This syndrome is very new. Before the discovery of its relevant gene, it was first described in 2004 when three children showed symptoms like infantile parkinsonism-dystonia alongside high levels of a dopamine-related compound in their spinal fluid.
Later, genetic analysis revealed mutations in the SLC6A3 gene, as documented in Nature in 2021. This gene encodes the dopamine transporter in affected patients.
Researchers believe faulty dopamine transporters can impair dopamine regulation in the brain, affecting neurotransmission and causing symptoms from childhood to adulthood.
Since then, around 51 cases have been reported, but it is not known how widespread it could be. The exact prevalence of dopamine DTDS is not well-known because it is a rare disorder and is likely underdiagnosed.
Due to its rarity and the challenges in diagnosing it, particularly in less developed regions with limited access to genetic testing and specialized healthcare, the true extent of its occurrence in the population remains uncertain.
Additionally, DTDS may present with variable symptoms that overlap with other neurological or neuropsychiatric conditions, further complicating its recognition and diagnosis. Therefore, the prevalence of DTDS is not well-established.
For example, some scientists believe that these mutations are also linked to mental health conditions like autism spectrum disorder and ADHD. Researchers are now focusing on understanding the genetic variants and developing targeted treatments for DTDS.
What are the major neurological & mental health disorders related to the dysfunction of dopamine apart from Parkinson's disease?
As documented in this 2021 paper published in Neuroscience Letters, dysfunction of dopaminergic signaling may lead to a series of developmental disorders, including attention-deficit or hyperactivity disorder, autism, and schizophrenia. However, the exact roles of dopaminergic signaling in these diseases are far from fully understood.
In addition, this 2017 review paper in Nature informs that although neurobiological underpinnings of bipolar disorder are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades.
Researchers mentioned that the increased use of antidopaminergics in treating this disorder and new in vivo neuroimaging and post-mortem studies make it timely to review this theory.
A comprehensive 2021 review paper published in MDPI’s Biomedicines explained that dopamine has been studied extensively for its neuronal handling and synaptic actions. However, dopamine receptors can be found extra-synaptically, and, in addition, they are not only expressed in neurons but in many types of mammalian cells, inside and outside the central nervous system.
The paper mentioned that recent studies showed a dopamine link between the gut and the central nervous system. The mechanisms are unknown, but they probably require cells to act as mediators and the immune system's involvement.
These researchers informed us that dopamine receptors are expressed in almost any cell of the immune system, and dopamine regulates various processes, such as antigen presentation, T-cell activation, and inflammation.
This likely immune cell-mediated linkage opens up a new perspective on using dopamine-related drugs, such as agonist–antagonist–allosteric modulators of dopamine receptors, in various diseases.
Summary of Disease Mechanisms
As the MDPI paper is comprehensive and complex, I will summarize the most critical points and mechanisms using other peer-reviewed papers.
Despite being primarily produced by neurons, dopamine acts locally in various cells with dopamine receptors rather than traveling through the bloodstream like a typical hormone.
Dopamine influences cellular communication and functions in different settings, such as the immunological synapse, where dendritic cells interact with lymphocytes.
Dopamine’s role extends to the immune system, affecting T lymphocytes and dendritic cells’ functionality and potentially contributing to autoimmune diseases.
While dopamine’s actions on lymphocytes can be harmful, targeting dopamine receptors presents therapeutic opportunities, particularly in autoimmune disorders and anti-tumor activity modulation.
The breakdown of dopamine involves two enzyme-driven steps, resulting in a molecule called homovanillic acid (HVA). Healthy people's urine can detect HVA. Changes in HVA levels in urine and cerebrospinal fluid (CSF) indicate dopamine metabolism in neurological disorders.
For instance, elevated HVA levels are associated with certain brain injuries, while low levels are linked to infectious diseases and perinatal stroke. Imbalances in dopamine-related systems can result from changes in enzyme expression or genetic variations.
Spontaneous dopamine oxidation can produce harmful byproducts like aminochrome, which contribute to oxidative stress and potentially damage dopaminergic neurons.
This 2019 paper in the Journal of Neuroscience Research explains that dopamine signaling in the striatum is critical for various behaviors, including movement, behavioral flexibility, response to reward, and many forms of learning. Alterations to dopamine transmission contribute to pathological features of several neurological diseases, including Huntington’s disease.
The paper highlights that Huntington’s disease is an autosomal dominant genetic disorder caused by a CAG repeat expansion in the Huntingtin gene. The striatum preferentially degenerates in Huntington’s disease, and this region receives dopaminergic input from the substantia nigra, which also affects BDNF.
This 2018 paper in Biological Psychiatry states that Tourette syndrome is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial.
“Existing hypotheses suggest that Tourette syndrome involves supersensitive dopamine receptors, overactive dopamine transporters that cause low tonic but high phasic dopamine, presynaptic dysfunction in dopamine neurons, or dopaminergic hyperinnervation.”
This 2017 paper in the Journal of Neuropsychopharmacology informs 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.
Dopaminergic activity is complex and regulated by multiple brain structures, including the hippocampus's ventral subiculum and the basolateral amygdala.
The review explored the current information regarding the afferent modulation of the dopaminergic system and its relevance to major depressive disorder, as well as some of the system-level effects of novel antidepressants such as agomelatine and ketamine.
Enzymes in dopamine production and breakdown are crucial in maintaining normal dopamine levels and physiological functions. Drugs that affect these enzymes can impact dopamine transmission, with some medications showing potential for neuroprotection.
Do tyrosine supplements cause dopamine imbalance?
Tyrosine is an amino acid that serves as a precursor for norepinephrine and dopamine synthesis in the brain. We get tyrosine from food. Increasing tyrosine intake could lead to increased dopamine production, which might affect dopamine balance.
However, the body tightly regulates dopamine levels through complex feedback mechanisms, and consuming tyrosine alone is unlikely to cause significant imbalances in dopamine. We don’t have much evidence yet.
However, a 2015 study in the Journal of Psychiatric Research concluded that tyrosine effectively enhances cognition, but only when neurotransmitter function is intact and dopamine and/or norepinephrine are temporarily depleted.
I take 350 mg of N-Acetyl Tyrosine on stressful days and have never had any side effects. That said, excessive supplementation with tyrosine or other dopamine precursors could theoretically lead to imbalances or disruptions in dopamine metabolism, especially in people with pre-existing neurological conditions or those taking medications that affect dopamine levels.
Additionally, individual responses to tyrosine supplementation may vary, and some people may experience side effects such as gastrointestinal discomfort or mood changes. Therefore, it is wise to approach supplementation with tyrosine or any other amino acid with caution and under the guidance of a healthcare professional.
Conclusions
Understanding the complexities of neurotransmitter regulation, particularly dopamine, is essential for comprehending the pathophysiology of these disorders.
These disorders highlight the critical role of dopamine in various aspects of brain function, including motor control, cognition, emotion, and reward processing.
Dysregulation of the dopamine system can have profound effects on behavior and mental health and contribute to various neurological disorders that I outlined in this story.
Through this concise exploration of dopamine-related dysfunctions, I aimed to highlight the importance of recognizing and addressing dopamine imbalances in scientific and clinical settings, paving the way for more effective management strategies and targeted treatments.
I’d like to provide a few practical tips to balance dopamine and prevent its dysfunction with healthy lifestyle choices.
Takeaways
Limit excessive screen time, especially with instant gratification devices like smartphones, video games, and social media platforms. Overstimulation from screens can desensitize dopamine receptors and contribute to addictive behaviors.
Maintain a balanced lifestyle and refrain from hedonistic tendencies. Practice mindfulness and meditate. Limit stimulant intake, including nicotine, and avoid recreational drugs.
Engage in rewarding activities that naturally boost dopamine levels in a healthy way, such as exercise, gardening, a little sun exposure, dancing, creative pursuits, social interactions, and achieving personal goals.
When you notice addictive behavior, excessive agitation, discomfort, and other symptoms mentioned in this story, obtain timely support from qualified healthcare professionals like psychiatrists, psychologists, or neurologists.
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.
But when they are created artificially, the brain knows it through its punishment pathways, which I discussed before in a story titled The Neurobiology of Punishment and Pleasure Regulation in the Brain, which you can find in a Google search.