Neuroendocrine and Autonomic Dysregulation in Bipolar Disorder

If the sympathetic nervous system [which is part of the autonomic nervous system ] is unable to function properly because parts of it are broken or injured, then this would more than explain the neuroendocrine and autonomic dysregulation in Bipolar Disorder.

The vital signs are part of the autonomic nervous system [made up of neurons all over the body [see last post] that ensures proper underlying physiological function of the entire body. This makes measurement of the vital signs, especially in chronic stress, a key indicator of whether the sympathetic nervous system is working properly or not. It is clear that, in bipolar depressive episodes, the stress alarm is being set off by the sympathetic nervous system branch of the autonomic [and unconscious] nervous system [which works without our having to think about it]. We clearly have not found the basis for the alarm going off so loudly and desperately and chronically . We thought of stresses we all have experienced, that the patients might be experiencing, stresses such as being shamed, shunned, having poor hygiene habits, having poor social skills, failing in school, at work, in love, in friendship, divorce, death of loved ones, grief, having no money, etc.. I could go on and on. Life is difficult and often, life events are hard to navigate and we all need psychological and social support always, even when things are going well.

But none of these explains neuroendocrine or autonomic dysregulation in any disease syndrome.

Because some stressors are different. Some stressors involve the proper working of the autonomic nervous system of the body. And no one is aware of problems with the function of the autonomic nervous system that runs the body and the brain and the heart and the muscles and the blood and the organ systems and the rest. They work automatically so that we can be free to do whatever we want to. Our ability to think, to remember, to go to work or school, to deal with life events- good or bad-, depend on the seamless organization of our autonomic nervous system.

And the autonomic nervous system speaks loudly through physical signs that are vital to its proper function, especially during periods of metabolic and mechanical and physical and chemical stress, biotic and abiotic stress[ terms that are usually applied to plant stressors].

Alterations in HPA axis in bipolar illness and signs of excessive sympathetic nervous activity in bipolar illness point to a very serious problem; and this serious problem might involve the function of the autonomic nervous system itself, which of course might be aggravated by the presence of life stressors but are not the same as the presence of life stressors. Helping the patient deal with a life stressor may be helpful but life stressors are not the source of the problem with the A.N.S [the autonomic nervous system]. This is why help with life stressors and social support cannot be the only answer.

It may be necessary to probe the function of the A.N.S., especially its alarm system- its S.N.S. [sympathetic nervous system] to see if this system is signaling that it needs assistance in order to maintain homeostasis- a stable chemical and physical environment enabling the body [and brain] to function normally, so that we can freely go about thinking’s and working towards our goals and our dreams, free of illness or disability. Finding whether or not there is a physical or chemical or mechanical damage or injury to the nervous system that is holding back a proper and healthy and effective stress response to a [mostly] metabolic stressor . I describe what constitutes a metabolic stressor in the previous blogpost.

Neuroendocrine and Autonomic Dysregulation in Bipolar Disorder

Alterations in HPA axis function in bipolar disorder have been well substantiated (168). Exaggerated release of corticotropin-releasing factor (CRF) contributes to greater adrenocorticotropic hormone (ACTH) secretion and a subsequent elevation of circulating glucocorticoids (i.e., cortisol) (168). These disturbances are most likely attributable to deficits in cortico-limbic regulation in bipolar disorder, with consequent amygdala over-activity, and a compromised hippocampal regulatory role (169). Moreover, glucocorticoid receptors appear to have diminished sensitivity in mood disorders, possibly due to elevation in inflammatory cytokines, thereby disrupting physiological feedback regulation on the HPA axis and immune system (170172). Indeed, even euthymic bipolar patients exhibit a flattening of the cortisol curve (an ominous indicator of compromised overall health) compared with healthy controls. In patients unfortunate enough to have suffered multiple episodes, these abnormalities intensify, resulting in higher overall cortisol levels in addition to aberrant reactivity, and even greater flattening of their cortisol curves, compared with patients who have experienced only a few episodes (173). Highlighting the relevance of these neuroendocrine abnormalities, a recent study has associated elevated evening cortisol levels in bipolar individuals with a history of suicidal behavior (174).

In addition to HPA dysregulation, bipolar disorder may be associated with excessive sympathetic nervous system (SNS) activity. For example, extra-neuronal norepinephrine was reported to be elevated in a group of bipolar patients relative to healthy controls (175). Autonomic dysregulation, more generally reflected by decreased parasympathetic activity and elevated sympathetic activity, may be a trait marker for bipolar disorder, as indicated by a report of markedly lower heart rate variability in euthymic bipolar patients than in healthy controls (176). The constellation of SNS overactivity, parasympathetic withdrawal, glucocorticoid receptor insufficiency, and elevated inflammatory signaling may help account, at least in part, for the increased risk of metabolic syndrome, endocrine disorders, and vascular disease seen in bipolar patients (168177). Highlighting the relevance of this pattern of neuroendocrine, autonomic and immune changes is the fact that vascular disease has recently been identified as the leading cause of excess death in bipolar disorder (178).

In addition to affecting autonomic and immune function, elevated glucocorticoids have been associated with suppression of thyroid-stimulating hormone secretion and compromised enzymatic conversion of relatively inactive thyroxine to active triiodothyronine (172). An ensuing low-grade thyroid dysfunction has been associated with bipolar disorder and most likely influences both the clinical presentation and the treatment response (179180). REVIEW article Front. Psychiatry, 25 August 2014 | Integrated neurobiology of bipolar disorder Vladimir Maletic1* and Charles Raison2,3

Vital signs and their measurement, especially in mood and brain dysfunction, represents an attempt to investigate the integrated neurobiology of illness, especially of severe syndromes of neuropsychiatric illness, in particular the integrated neurobiology of bipolar attacks.

Kraepelin did this in the years leading up to his death in 1926 and he found significant results AND no one followed up on his work since.

No one could do anything then about the ventilatory defects/injuries he discovered hindering a proper SNS defence against the elements of this planet so psychiatric medicine did what it could.

In the 21st century, we can rescue the function of the sympathetic nervous system, even if, as Kraepelin suspected, the ventilatory system was permanently damaged. We can help the sympathetic nervous system to protect against metabolic insults, with supportive medicines [some of which we have not yet discovered] and supportive treatments used in rehabilitative medicine and with better controls agains infections and better knowledge of and avoidance of environments in which there is possible chronic exposure to combustable fuel products indoors and outdoors. [again, see the previous blog post for details.

And it is clear, that if the SNS is permanently compromised in its function of protecting the body, then, the cardiovascular system will need immediate assistance because no one can afford to have thermoregulatory problems affecting the heart, circulatory issues affecting the heart or anything at all affecting the proper function of the heart!

stages of Failure of the heart is a clear consequence of ventilatory failure, if indeed, ventilatory failure is found in bipolar depressed patients. A first and easy step towards Beginning an investigation of the neuromuscular ventilatory system [separate from the lungs] is to carefully and mindfully measure the respiratory rate at rest manually or with the help of technology, in order to see if it can react during metabolic stressors. If not, other easy non invasive tests can be conducted.

Failure of the brain is another clear consequence of stages of ventilatory failure, for obvious reasons of physiology. [for details read all my previous blogposts].

Failure of normal mood is another clear consequence of stages of ventilatory failure while still alive and ambulatory. Again, read previous blogposts on mood and hypercapnia.

Failure of the SNS may not be fixable; at least it is not in Paula’s case or does not seem so, BUT the function of the heart , of thermoregulation, of the brain and of mood CAN be improved or even fully rescued because the metabolic and chemical effects of ventilatory failure can be reversed completely with medical and nutritional and rehabilitative support.

Paula has completely recovered her baseline good health, good mood, good brain function, with now mediocre circulatory function [she is 67 years old and relying on me – a layperson- and Paxil, to help manage her chronic condition.

To be continued!!!!


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