Last Updated on 10 December 2024
Bipolar disorder is the most disruptive form of atypical depression, and the main cause of disability among people with mental illness. The most relevant features of this chronic mental disorder are mood swings oscillating between excitation, called mania, and depression.
Several studies tried to discover the causes of bipolar disorder. The most discussed and theorized among these ones is an imbalance in neurotransmitters.
But is neurotransmitter imbalance a cause of bipolar disorder or is the contrary?
This article tried to answer this still unresolved and complex question.
What Science Says
Neurotransmitters are molecules the brain produces to regulate and modulate emotional and non-emotional functions.
These molecules have been found to be abnormal in bipolar patients.
According to a study published in 2022 by the journal of Clinical Psychopharmacology and Neuroscience, in bipolar disorder, neurotransmitters are abnormally regulated in the brain. Biogenic amine neurotransmission functions in the limbic system are impaired, influencing sleep, appetite, alertness, sexual function, endocrine function, and the regulation of emotions such as fear and anger.
The neurotransmitters involved in the pathogenesis of bipolar disorder are noradrenaline, serotonin and dopamine.
Noradrenaline controls the levels of energy. Studies found that noradrenaline activity is high in mania.
Serotonin, conversely, regulates mood, and is also known as the hormone of happiness.
Serotonin levels are low in unipolar depression, while no difference has been found among bipolar and unipolar patients.
Dopamine, instead, is the neurotransmitter heavily involved in the genesis of bipolar disorder.
That is a neurotransmitter the brain produces to regulate not only emotions, but also movements and heartbeat.
In animal model studies, dopamine is high in mania and low in depressive episodes.
The dopaminergic system is in the midbrain and regulates motivation, reward, expectation, sensation of pleasure and compensation circuit.
Interaction Between Dopamine and Bipolar Disorder
How dopamine and bipolar disorder interact among them is not fully understood, yet.
It is possible dopamine influences bipolarity, but it is also likely bipolar personality affects dopamine levels. It is a mysterious link that doctors and researchers find hard to unravel, but which is pivotal to turn bipolar disorder into a curable mental disease, or rather, into a condition that can go into remission.
This detail is not pointless, because bipolar disorder is a mental illness that may have a detrimental impact on the brain functions.
Dopamine, – the study reads – more than other neurotransmitters, has been implicated in the transition of depression to a manic episode in bipolar disorder. This theory is supported by the following evidence: manic episodes typically occur at the time of administration of the dopamine precursor L-dopa.
Neurotransmitter Imbalance from Bipolar Disorder
Another study on bipolar disorder published in Brain Sciences discussed the hypothesis of neurotransmitter imbalance induced by bipolar disorder.
Researchers, in fact, hypothesized there would be a sort of neuroprogression in this mental illness.
In short, over the course of the disease, bipolar disorder may impair neuronal circuitries and neuroplasticity, inducing changes in the brain.
Brain image scans, in fact, discovered that the brain of bipolar patients is thinier, and some areas have a minor volume.
According to the aforementioned study, mania and depression may have cumulative impact in neuronal cells, such as neurons and glia.
In turn, the neuronal damage might result in neurotransmitter imbalance.
Another neurotransmitter could be involved or impaired in bipolar disorder. That is Gamma-aminobutyric acid (GABA). Gaba influences intraneuronal transmission in regions of the brain which control mood, such as striatum and cerebral cortex.
Clinical trials showed that GABA was low in depression, and high in mania. But the main question always remains: are neurotransmitters that don’t work in bipolar disorder or is the latter that damages them?
A further explanation of the connection between neurotransmitters and bipolarism is neuroendocrine.
There is evidence the neuroendocrine system is impaired in people with bipolar disorder. This system consists of the hypothalamic-pituitary-adrenal cortex axis and regulates stress response.
In psychiatric illnesses, such as bipolar disorder, stress response is dysregulated, but this dysregulation might be the consequence of a long course of bipolar disorder. As you can see, the cause effect ratio is always doubtful in this case.
It is also frequent that people affected by thyroid disease and autoimmune thyroiditis experience depression and other psychiatric illnesses, including bipolar disorder. This happens because thyroid diseases and autoimmunity are strongly linked to the onset of bipolar disorder and neurotransmission impairment.
There is also evidence that thyroid hormones influence the neurotransmitter activity in the brain, and metabolism of serotonin and catecholamines. The latter is a group of molecules including dopamine, adrenaline and noradrenaline. They are all involved in the mechanism of stress response and fight or flight reaction.
Hypothyroidism, for instance, is also able to impair the transmission of serotonin in the brain, and trigger depressive symptoms.
However, bipolar disorder and neurotransmitter imbalance can occur even in euthyroid people, but the disorder is very common in patients with autoimmune thyroiditis in euthyroid stage. In this case, the culprit of bipolar disorder and neurotransmitter imbalance may be autoimmunity, or rather, the inflammatory cytokines that attack the thyroid gland.
These cells are able not only to impair the signal of transmission of serotonin, but they can also damage the transmission of other neurotransmitters, such as dopamine.
Moreover, studies found that dopamine is an important mediator between the nervous system and immune cells. It operates in the regulation of the immune response, and its dysregulation could cause autoimmunity. In turn, the latter might trigger mental disturbances such as bipolar disorder.
The role of autoimmunity in the onset of bipolar disorder has also been investigated and discussed in a study published by BJP, the Brazilian Journal of Psychiatry, according to which immune dysfunction in BD is supported by pre-clinical and clinical evidence showing elevated levels of pro-inflammatory cytokines, including interleukin-4 (IL-4), interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, soluble interleukin-2 receptor (sIL-2R), and soluble receptor of TNF-type 1 (STNFR1).
Furthermore, it is believed that mood stabilizers do not work in autoimmune mediate bipolar disorder.
Just think that thyroid hormones are being proposed as a therapy to treat resistant bipolar disorder. But the results are not confirmed yet.
Bipolar and Neurotransmitter Dysfunction in Neuroimaging Studies
Another possible explanation about bipolar disorder and neurotransmitter dysfunction might be an emotional dysregulation in the brain circuits that control mood and reward. Indeed, DTI (Diffusion Tensor Imaging) studies – the Brazilian clinical report says – have shown consistent abnormalities in regions associated with emotional regulation as well as in structures that integrate these regions interhemispherically.
Mood and reward circuits are located in the region of the brain called striatum, where presynaptic nerve cells activate the neuronal transmission of dopamine. The dopamine signal arrives in the postsynaptic neuron which receives it.
Hence, if mood regulation and reward circuits do not work properly, one can experience exaggerated emotional reactions that may coincide with the classical symptoms of bipolar disorder.
There are in fact people who are extremely sensitive to emotions such as expectation and reward. If the expected reward does not arrive, they can become heavily excited, depressed, and emotionally dysregulated. I am one of these people.
Diagnosed with Hashimoto’s thyroiditis at 12 years old, I started having emotional dysregulation at 19. Diagnosed in 2008 with bipolar disorder (bipolar 1), I was unaware that my bipolarity actually was a neuroprogressive disease capable of damaging the brain over time. Indeed, three years ago, I was diagnosed with Parkinson’s, after over 30 years of bipolar disorder and mood swings.
Movement and mood, unfortunately, have in common the same brain circuits and the same areas. Emotional fluctuations and movement disorders become thus the same clinical feature of an identical dysfunction. Studies including the ones I mentioned in this article show that bipolar disorder can accelerate the brain ageing, with neuronal and dopaminergic transmission impairment.
How Bipolar Dysregulation Works
Reward sensitive people, also known as neurodivergent, have a brain structure that is similar to the ones of drug addicted persons.
In drug addicted patients, dopaminergic peaks play a crucial role. The drug addict needs the addictive substance to experience extreme gratification. When the gratification goes up, it means the brain is producing high quantities of dopamine.
But when the addictive drug goes down, dopamine goes down, too, causing severe depression.
It is not by chance that when one removes the addictive drug, withdrawal occurs with tremors, movement disorders and parkinsonian symptoms. People who experience Parkinson due to drug consumption have, in short, the so-called traumatic Parkinson.
When one is reward addicted, the mechanism is similar, but doctors don’t talk about traumatic Parkinson’s, because one didn’t take addictive substances. They talk of genetic Parkinson.
Nowadays, many conditions are promoting reward addiction. Marketing, social media, and motivating messages push more and more people to chase fallacious sensations of pleasure and satisfaction, upon the guide of a mechanism orchestrated to make perennially unsatisfied and fuel the compulsive action of buying.
My hope is that science discovers how to improve the quality of life of the affected patients. And, above all, I wish those who engineered the perverse strategy of expectation and reward will be punished by justice as they deserve. On and off-line.
Causes of Dopamine and Reward Dysfunction in Bipolar Disorder
In bipolar disorder, dopamine and reward dysfunction may always be behind the corner. This psychiatric illness is indeed known as bipolar affective disorder.
The causes of dopamine and reward dysfunction in bipolar disorder are not fully understood, yet, but they can be:
Genetic
Environmental
Psychosocial
Hormonal
Endocrine
Neuroendocrine
Inflammatory
Metabolic
Or can derive from:
Oxidative Stress
Mitochondrial Dysfunction
mRNA damage
BDNF (neurotrophic factor) deficiency
Or from a complex interaction among a few or all the mentioned causes.
A proposed therapy to treat dopamine reward dependency and related dysfunction is with glucocorticoids, hormones naturally produced in the adrenals and spread in the brain cortex, as well, which are able to regulate stress response.
Conclusion
The information contained in this article comes from medical sources and my same clinical experience as a patient. Further clinical trials performed on postmortem brain found that genes such as C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 are important in the pathogenesis of schizophrenia and bipolar disorder; these two disorders share common disease-related mechanisms linked to altered dopamine signaling.
Hence, the neurotransmitter imbalance in bipolar disorder is more than confirmed.
