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Neurochemistry and Endocrinology in Bipolar Disorder

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D., edited by Kathryn Patricelli, MA Updated: Feb 27th 2017

Bipolar Disorder and Neurochemistry

The brain uses a number of chemicals as messengers to communicate with other parts of the brain and nervous system. These chemical messengers, known as neurotransmitters, are essential to all of the brain's functions. Since they are messengers, they typically come from one place and go to another to deliver their messages. Where one neuron or nerve cell ends, another one begins.

brain and neurons In between two linked neurons is a tiny space or gap called a synapse. In a simple scenario, one cell sends a neurotransmitter message across this gap and the next cell receives the signal by catching the messenger chemical as it floats across the gap. The receiving neuron's capture of the neurotransmitter chemicals alerts it that a message has been sent, and this neuron in turn sends a new message off to additional neurons that it is connected to, and so on down the line.

Neurons cannot communicate with each other except by means of this synaptic chemical message. The brain would cease to function in an instant if chemical messengers were somehow removed. By providing a way for allowing neurons to communicate with one another, neurotransmitters literally allow the brain to function. There are millions and millions of individual synapses, or gaps, in the brain. The neurotransmitter traffic and activity happening inside those gaps is constant and complicated.

There are many different kinds of neurotransmitter chemicals in the brain. The neurotransmitters that are suspected to be involved in bipolar disorder include dopamine, norepinephrine, serotonin, GABA (gamma-aminobutyrate), glutamate, and acetylcholine. Researchers also believe that another class of neurotransmitter chemicals known as neuropeptides (including endorphins, somatostatin, vasopressin, and oxytocin) play an important role in both normal brains and those brains with bipolar disorder.

Measuring neurotransmitters, their chemical variations, locations, and their effects is a large area of study in bipolar research. It is known that these chemicals are in some way unbalanced in the brain of a person with bipolar disorder compared to the brain of someone without the condition. For example, GABA is observed to be lower in the blood and spinal fluid of patients with bipolar disorder, while oxytocin-active neurons are increased in those with bipolar disorder. However, the role of these findings to overall brain functioning is not yet understood. Whether the presence, absence, or change in these chemicals is a cause or outcome of bipolar disorder remains to be determined. The importance of neurochemicals in creating bipolar disease cannot be denied.

Bipolar Disorder and Endocrinology

Neurotransmitters are not the only important chemical messengers in the body. The body also uses hormones as chemical messengers. Produced in the endocrine system, hormones circulate from one organ to another through the bloodstream. Receiving organs in the body interpret hormonal signals and respond to their messages.

The endocrine and nervous systems are linked by the hypothalamus. This is a centrally located 'switching station' within the brain. The hypothalamus is an exceptionally complex brain region. It controls many different body functions such as blood pressure, appetite, immune responses, body temperature, maternal behavior, and body rhythms dealing with circadian and seasonal rhythms. This coordination of circadian and seasonal body rhythms is particularly important when discussing bipolar disorder. (See our section below on Body Rhythms for more information).

The thyroid is an endocrine organ located in the neck that produces thyroid hormone. It has been the focus of much mood disorder research. Depression is frequently associated with low levels of thyroid hormone, a condition known as Hypothyroidism. Mood elevation is often associated with high levels of thyroid hormone (Hyperthyroidism). Treating hypothyroidism by supplementing or replacing thyroid hormone may sometimes alleviate depression. Similarly, reducing levels of high thyroid hormone with lithium may ease manic symptoms. Given that up to half of patients with a rapid cycling form of bipolar disease also have hypothyroidism, the involvement of the thyroid gland in producing or enabling bipolar disorders for some patients is a strong possibility.

Another component of the endocrine system which is known to cause mood fluctuations when not being regulated correctly is the reproductive system. As reproductive hormones are known to affect mood, most prominently in women, the source of this effect is thought to be the ovaries which secrete estrogen and testosterone. Although the role sex hormones play in mood conditions are well documented (See our earlier discussion concerning PMDD), exactly how these hormones affect mood is unclear. There is little information available currently regarding their possible role in causing or maintaining bipolar symptoms.

Because of the connections between the nervous and endocrine systems, it is thought that endocrine dysfunction is a potential cause of bipolar disorders. Though this may not be a surprising conclusion, it is a difficult one to establish scientifically. It has proven difficult to determine whether endocrine dysfunction is a cause of bipolar disorder or an effect of the condition being present.


Reader Comments
Discuss this issue below or in our forums.

To the woman above with the cycling husband on synthroid - Ally - Jan 13th 2010

Medicine in shot form for bipolar - Chantel Black - Dec 16th 2009

I'm 41 years old and i have bipolar and i rather take medicine in a shot form instead of taking pills every day, get a shot between once a month, or one shot every two months or even one shot every three months. Is better than taking a pill every day just like they have the birth control shot. I want and rather a shot form medicine for my bipolar at least can people get a choice pill or shot. shot form for other problems as well ADD,depression,ADHD,Personalily disorder Bipolar and Schizophrenia. please work on this very,very soon it will be a help to alot of people who forgets and lazy people to who just want take any medicine to get better and terrizorise people on their job,or family in the home or at school or in public that's why a shot form would be better for some people life style than a pill would.

Manic or Burned out at Ma Bell ??? - Nastova Dina Rogne Andresdautter - May 9th 2009

5/8/2009  Very informative.  I was diagnosed as "Manic-Depressive" in 1988 at the age of 37.  I've gone with that diagnosis. I was also being treated for an underactive thyroid and still am. It is good to know that there may be a "connection". As I have no children, I didn't have to be hospitalized. My husband cared for me at home until I got through the worst and could manage to be home alone. I have never had negative thoughts nor thoughts of harming myself or anyone else. I have a family history of "Bi-Polar Disorder". My father told me that he had this and had been hospitalized twice.  It seems to "rear it's head" most often when I am under stress. This was the case in 1988.    I had senority and my Co-workers wanted my vacation pick and were unconvinced that I wasn't interested in the job transfer that they wanted.  6 or more were constantly "dinging" on me. Myseriously, I became violently ill while drinking water from a large 48 oz mug that I kept unattended on my desk. My supervisor was off that day. I was out 3 days. I received a warning and I was not eligable to transfer for a year. At the time I didn't suspect that my water may have been spiked with something like visine...   within a few weeks I suddenly went into a catatonic state at work. My supervisor was off this day as well. I told my husband as best as I could that perhaps something had been put into my water. In the 48 oz mug left unattended on my desk...   even over night. I was not believed and was diagnosed as "Manic" (Due to family history). My physcian did call my co-workers "Those Sharks !!!"...   so perhaps he may have seen some relavance in my claim. My husband did not...   until just recently.  Perhaps I was "pushed over the edge". Perhaps I was done a favor by an early diagnosis. Perhaps I am "Hypo-manic. Perhaps I am not even "Manic". I have never again been "catatonic" and felt so increadably high and felt "really really good" for no apparent reason...   Unless it was induced or actually a bout of Mania. I don't use drugs nor alchol. I prefer to be sane and sober !!!   I worked at one company for 35 years and I've been married for 31 years. I've always "dug my heals in". I'd say that this isn't what I've heard about the typical Bi-Polar patient. Is financial problems, job changing and marriage failures more frequent in Bi-polar patients than in the average population? I don't know...   but it was so with my Dad.

Hormone Levels and Diabetes - Ms Lowery - Apr 14th 2009

I was at the age of 18 diagnosed with very low hormone levels and borderline diabetes.  I was also told that I woud likely not be able to have children.  I never had menstation periods without the help of shots or birth control pills.  It came to be that I could not take birth control pills.  So I suffered for years with irregular periods or no periods. During this time my moods became so bad that I had to take medicine for depression and anger. I was diagnosed as having (PMS) Pre-Menstral Syndrone. Somehow during this time I was able to work using lots of sick leave.  I knew when I got up in the morning whether I could go to work or not by my mood.  I used my leave as fast as it was earned (vacation time and sick leave). Finally at the age of 45 when I was going through Menopause I was prescribed hormone medicines as the doctor stated my hormone levels were so low as to have none.  Two year later the diabetes was so bad that I that I had to go on medication. At 47 my anger moods affected my working life and  my employer stated that I had to go to anger management classes.  It was at this time that I was diagnosed with bi-polar mania.  I had to take 6 weeks off work and many trips to the mental health doctors to get my medicine right.  At 59 I am still having to have my medications ajusted and see my doctors.  My health is much better and I retired after 35 years of work.  I wish I was diagnosed years earlier so I  would not had to suffer so long.  Does all of the above sound familiar.   I definitely believe that hormones and our endocrinology systems are to blame.

Endocrinology & Bipolar Disorder - Brandy Drum - Mar 19th 2009

I was so happy to find this website that I started crying.  I'm glad to know someone else thinks bipolar has a lot to do with hormones. I went into a full-blown manic eposide when my daughter was three months old.  My family and I had no idea what was going on.  That was 10 1/2 years ago & many hospitalizations later and I still feel the mania right now running through my body.  My mom & the cops that had to escort me to the hospital noticed that my eyes were dilated when I was manic. They thought I was on drugs even though I have never done drugs in my life.  My tox screen was clear and I was put in a psych hosptial and given shot after shot of Ativan and Hadol just to make me sleep. My body was completely exhausting itself.  One patient wouldn't even sit by me in the hospital because my eyes were so dilated he said I looked possessed.  I was high as a freaking kite and felt like I could pull myself out of the top of my head.  I was talking so fast that I was drooling.  This happens everytime I get manic.  I take my medicine but it only half-way works for me because it's not getting to the real source of the problem. When it cycles I feel like there is nothing I can do but take Ativan to go to sleep or I will end up back in the hospital.  I asked the psychiatrist that evaluated me for nursing why my eyes kept dilating and he thought for a minute and said "adrenaline"  That makes perfect since because our adrenal glands deal with stress & our fight or flight response (emergency system).  I know this disease has to do with the neurotransmitters, but it has just as much to do with hormones in both men and women.  I get the good "Rock Star" highs, but I also get the rages when it's time for my period.  In a way this is the coolest, but deadliest disease you can have.  I will donate my body to research (we are most useful to science when we are alive!) and I will do whatever I need to do to prove that this at times can make us crazy, but it's not "all in our heads".  I hope my 10 years of hell helps someone.  I also want to tell everyone that I have polycystic ovarian disease, thyroid disease (maybe caused by lithium, maybe not), and hypoglycemia which  all has to do with the endocrine system.  Anyone that wants to discuss this with me or know how I can be researched please e-mail at  I'm tired of people dying, self-medicating and just losing their quality to life over a disease that can better understood and better medications made available.  There are doctors and researchers out their that already have the gift to be able to figure this out.  They just need us to get together and tell them exactly what is happening in our bodies. This disease is hard to live with, but the more I know about the disease the more interesting it is.  God Bless!  Brandy

connections - - Jul 29th 2008

I would like to thank you for this article, it has helped me connect the dots so to speak.  I was diagnosed with diabetes type II at age 24 at 140 lbs at age 30 with premature ovarian failure, hypothyroidsm and fibromyalgia and to boot I am bipolar.  I still need information on the connection between all my stuff but am glad I am not the only one and how articles like this help solve the puzzle as to not blame myself or feel like such a weenie.

synthroid, testosterone and bipolar - jean - Jul 13th 2008

Thanks for the endorine/bipolar article.  My husband is taking effexor, a testosterone cream, and synthroid.  When he cycles, which we still can't predict, he goes through a hypersexual phase, either with or close in time to an anger phase with me, his wife.   They want him on the testosterone, since his blood levels are very very low, but yet when he cycles, it seems like he's got too much testosterone.  If anyone has been through this and has an idea, I'm all ears, please email me.

endrocine dysfunction vs. bipolar disorder - jsc - Jun 30th 2008

at 48 years of age I went into a perimenopausal state which exacerbated my depression into high gear...this threw me into mania in which I penned three books...both body and mind have never been so uncomfortably 'heightened' and I have yet to find the drugs to help...I underwent a bil. mastectomy for atypical breast disease and hormonal therapy is allowed and some of the medications are difficult to take...I 'strongly' believe that the endrocine system is of the 'utmost' cause in my disease process and lack of well-being...I also suffer with male pattern alopecia from teen years...what more could I do but try to accept it...

- - Apr 13th 2008
Thanks for the news.  I have been thinking of going to see an endocrinologist for help.  It seems that everytime my hormones fluctuate My OCD gets worse.  I have been battling this for 4 years ever since I had my baby.  It is just devastating

Thanks a lot - - Nov 26th 2007
Your site provides the most comprehensive information on mental health. Thanks a lot.

!!!!!! That is what I was looking for!!!! - - Apr 15th 2007
THank you very much for this article! It is very interesting! I always wondered about th reasons of depression: is it the endocrine or j the psycological cause. THANK YOU!


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