Neurotransmitters

A Neuron is a specialized nerve cell that receives, processes, and transmits information to
other cells in the body. We have a fixed number of neurons, which means they do not
regenerate. About 10,000 neurons die everyday, but since we start out with between ten
and 100 billion (Hooper & Teresi, 1987), we only lose about 2% over our lifetime.

Information comes into the neuron through the Dendrites from other neurons. It then
continues to the Cell Body – (soma) which is the main part of the neuron, which contains
the nucleus and maintains the life sustaining functions of the neuron. The soma processes
information and then passes it along the Axon. At the end of the axon are bulb-like
structures called Terminal Buttons that pass the information on to glands, muscles, or other
neurons.

Anatomy of a Neuron
Information is carried by biochemical substances called neurotransmitters, which we will talk
about in more detail shortly. The terminal buttons and the dendrites of other neurons do not
touch, but instead pass the information containing neurotransmitters through a Synapse.
Once the neurotransmitter leaves the axon, and passes through the synapse, it is caught on
the dendrite by what are termed Receptor Sites.

Neurotransmitters have been studied quite a bit in relation to psychology and human
behavior. What we have found is that several neurotransmitters play a role in the way we
behave, learn, the way we feel, and sleep. And, some play a role in mental illnesses. The
following are those neurotransmitters which play a significant role in our mental health.

Acetylcholine –
involved in voluntarymovement, learning, memory, and sleep

Too much acetylcholine is associated with depression, and too little in the hippocampus has
been associated with dementia.
Dopamine –
correlated with movement, attention, and learning

Too much dopamine has been associated with schizophrenia, and too little is associated
with some forms of depression as well as the muscular rigidity and tremors found in
Parkinson’s disease.

Norepinephrine –
associated with eating, alertness

Too little norepinephrine has been associated with depression, while an excess has been
associated with schizophrenia.

Epinephrine –
involved in energy, and glucose metabolism

Too little epinephrine has been associated with depression.

Serotonin –
plays a role in mood, sleep, appetite, and impulsive and aggressive behavior

Too little serotonin is associated with depression and some anxiety disorders, especially
obsessive-compulsive disorder. Some antidepressant medications increase the availability
of serotonin at the receptor sites.

GABA (Gamma-Amino Butyric Acid) –

inhibits excitation and anxiety

Too little GABA is associated with anxiety and anxiety disorders. Some antianxiety
medication increases GABA at the receptor sites.

Endorphins –
involved in pain relief and feelings of pleasure and contentedness
Please note that these associations are merely correlations, and do not necessarily
demonstrate any cause and effect relationship. We don’t know what other variables may be
affecting both the neurotransmitter and the mental illness, and we don’t know if the change
in the neurotransmitter causes the illness, or the illness causes the change in the
neurotransmitter.

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. 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 synaptic junction and the next cell receives the signal by catching
the messenger chemical as it floats across the synapse in a receptor structure. 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.

Importantly, 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 mechanism for allowing neurons to communicate with one another,
neurotransmitters literally enable the brain to function. There are millions and millions of individual
synapses in the brain. The neurotransmitter traffic and activity occurring inside those synapses is
constant and complicated.

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

Measuring neurotransmitters, their chemical variants, locations, and their effects constitute a large area
of study in bipolar research. It is known that these chemicals are in some way unbalanced in the bipolar
brain compared to normal brain. For example, GABA is observed to be lower in the blood and spinal
fluid of bipolar patients, while oxytocin-active neurons are increased in bipolar patients, but the
relevancy of these findings to overall brain functioning in bipolar and normal individuals 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, but the importance of neurochemicals in creating bipolar
disease is indisputable

Bipolar Disorder and Endocrinology

Just as the brain relies on neurochemical messengers for communication, the rest of the body, including
the brain depends, in some part, on the endocrine system. The endocrine system uses hormones as
chemical messengers. Hormones circulate from one organ to another through the bloodstream. The
target or destination organ interprets the hormonal signals sent by the sending organ and acts on them
accordingly. Endocrinology is the branch of medicine dealing with the endocrine system and its specific
hormones. The endocrine and nervous systems are linked by the hypothalamus (a centrally located
'switching station' within the brain). The hypothalamus is an exceptionally complex region. with multiple
components that control many different body functions, including the regulation of blood pressure,
hunger immune responses, body temperature, and maternal behavior, just to name a few. Of particular
note with regard to bipolar conditions is the fact that the hypothalamus coordinates circadian and
seasonal body rhythms (See our section below on Body Rhythms for more information).

The thyroid, an endocrine organ located in the neck which produces thyroid hormone, has been the
focus of much mood disorder research. Depression is frequently associated with low levels of thyroid
hormone, a condition known as Hypothyroidism, while mood elevation is often associated with high
levels of thyroid hormone (Hyperthyroidism). Treating hypothyroidism by supplementing or replacing
thyroid hormone (in the form of Synthroid, for instance) sometimes helps alleviate depression. Similarly,
reducing levels of high thyroid hormone with lithium may ease manic symptoms. Given that up to half of
patients with 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
dysregulated 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, and there is
little information regarding their possible role in causing or maintaining bipolar symptoms.

Because of the connections between the nervous and endocrine systems, (e.g., hypothalamic
involvement in mood determination, and the effects of thyroid and ovarian hormonal imbalances on
mood) it is thought that endocrine dysfunction is a potential cause of bipolar disorders. Though this may
not be a surprising conclusion, it is nevertheless a difficult one to establish scientifically. It has proven
difficult to determine whether endocrine dysfunction is a cause of bipolar disorder or an effect.
1st

Serotonin has nothing to do with mood at all, except very indirectly. The reason that
serotonin boosters help clinical depression is that they increase cognitive flexibility and
allow you to break out of fixed, counterproductive thought patterns. (This idea, an original
one of mine from before 1998, has subsequently cropped up elsewhere.) You can have good
beliefs about yourself and the world, together with low levels of serotonin, and be blissfully
happy.

Dopamine was once thought to be associated with pleasure, but it’s actually about desire. So
the positive feeling (again according to me) that it mediates is strictly that associated
with looking forward to or anticipating something pleasurable. We find the anticipation
pleasurable in itself because it encourages thinking about the potential reward, and what we
might do with it when and if we get it. It it weren’t pleasurable to fantasize about a first date,
we wouldn’t think about it, and thinking about what we might do (“OK, that’s not a good
idea!”) can lead to a better first impression … which leads to the famous “reproductive
success” which is the secret deep rationale for all of our behavior. So the positive feeling of
dopamine is not happiness in the sense of being content or fulfilled. It’s passion, being eager
and full of life—which can of course co-exist with all sorts of misery.

The one fun fact that’s worth sharing about endorphins is that eating spicy food is
pleasurable because the brain reacts to the pain of capsaicin by releasing more than
enough endorphins to counteract the pain … so you come out ahead. I have a sleep disorder
that can mess with my brain chemistry, and I’ve had spells when my endorphin levels were
low, where I went from being able to eat a jar of the hottest hot salsa at one sitting to being
unable to tolerate a teaspoon.

2nd

If you are interested in neuro science, then this is very good question. Let me take a stab and
keep it as simple as possible.

Dopamine, Oxytocin, Serotonin and Endorphin is all “Happy” neuro transmitters and plays
a very critical role in our happiness quotient.

Dopamine: This is ‘Feel Good’ hormone which keeps you motivated and let you enjoy what
you really like. Why do you feel good…when you win a lottery, meet your sales target, catch
your train on time all.. or have your favorite ice cream… it all stimulate dopamine. Cannabis
or marijuana also make your brain release dopamine and that’s why folks get addicted to
this overdose of dopamine. On the other side of the spectrum, you might have met people
who only like talking about them self, it’s not their fault, it’s pure neuro science at work.
When somebody talks about them self, their brain releases dopamine and they want to
continue doing that.
Oxytocin: This is ‘Bonding” hormone which help you create stronger
bonds/trust/relationship with people around you. When a mother breast feeds her baby,
both release high amount of oxytocin leading to strong bonding between them. Also the
reason for bonding between couples/partners.. as this neuro transmitter is released during
the orgasm as well. Another example is, you tend to get closer to people with good sense of
humor, cause humor also help release oxytocin and you are more likely to bond with people
who makes you laugh.

Serotonin: This is what makes you ‘Feel important’…it plays a critical role in how you live
your life. A very simple way to keep the serotonin level up is by practice
acknowledging/remembering your past successes, happy moments and showing gratitude
to people around you. Folks with high suicidal tendency, or folks getting into anti-social
activities lacks this neuro transmitter in their blood. Eat bananas, get out in sun for 20
minutes, it helps release serotonin. It is also very important for a good night sleep.

Endorphin: I would call this a ‘Rock star’ hormone. This helps us overcome our stress and
pain caused due to physical activities. What do you think keeps a long distance runner or a
fitness freak focused on his/her regime? It’s the Endorphin which keeps them going. It helps
you recover from injuries and at the same time improve your immunity as well. Humor and
laughter also helps create Endorphin, that’s one of the reason docs recommend you to laugh
out loud.

Hope this give you an overview of these four pillars of our happiness..Ola.

3rd

Dopamine is an extremely complicated monoamine neurotransmitter. There are many

functions of dopamine that are still being elucidated today. There are two ways that
dopamine’s role in the brain are being studied: Top down and bottom up. Top down
examines the effects of dopaminergic drugs on mood and behavior. Bottom up examines
dopaminergic circuits, and their relation to behavior. Dopamine has many more roles than
the ones described below, but they are the major ones implicated in dopaminergic drugs.

From the top down view, we learned that dopamine is related to mood, reward, pleasure,
motor activity, and focus(1). Administration of dopaminergic drugs like amphetamines in
lower doses generally increases focus, energy and motor activity, while at higher doses can
cause euphoria and at even higher doses possible psychosis(2).

From the bottom up view we learned about dopamine on a cellular level. Dopamine is a
monoamine neurotransmitter derived from the hydroxylation of tyrosine into L-DOPA(3)
followed by the decarboxylation of L-DOPA to create dopamine(4). Dopamine is the
precursor to norepinephrine and epinephrine. It is incapable of passing the blood brain
barrier, and therefore has to be synthesized in the brain.(5) Dopamine binds to a variety of
metabotropic receptors, meaning it binds to receptors that have secondary messenger
systems that alter the excitability of cells.(6) These receptors can be classified into two
classes, D1 like and D2 like. The D1 like receptors result in up regulation of adenyl cyclase
and therefore increases intracellular cAMP. The D2 like receptors do the opposite(7).

There are four (sometimes classified as 3) main dopaminergic pathways in the central
nervous system. The mesolimbic pathway, the mesocortical pathway, the nigrostriatal
pathway and the tuberofundibular pathway.(8) The main ones involved in the major effects
of dopaminergic drugs are the mesolimbic, mesocortical and nigrostriatal pathways. The
mesolimbic/cortical pathways are sometimes contracted as one. The mesocortical pathways
is involved in attention(9) and cognition and activation of it increases attention. The
mesolimbic pathways is associated with pleasure and reward(10)(11)(12). Dopamine release
in the mesolimbic system acts as a signal that a stimuli is interesting or good. This feeling of
pleasure increases the chance that the steps leading up to it will be repeated again. The
nigrostraital system is involved in motor activity.

Dopaminergic pathways have been implicated in many disorders including but not limited
to, OCD(13), Depression and bipolar(14), ADHD(15), schizophrenia(16), eating
disorders(16), parkinsons, drug addiction and other psychotic disorders besides
schizophrenia. Although the role of dopamine is often debated and is not clear cut, a lot of
research does implicate dopamine in the pathophysiology of these disorders.

Serotonin is a monoamine neurotransmitter that is synthesized from the hydroxylation

and decarboxylation of tryptophan. It is a neuromodulater, with the majority of it being
found in the digestive tract, but it still has a major role in the CNS. We don't exactly know
what it does, however it has been implicated in sleep, pain perception, appetite,
wakefulness, attention, and sensory perception.

Serotonergic neurons are found in dense clumps called raphe nuclei, which project into the
whole cortex, the striatum, the ventral tegmental area, the substantia nigra, amygdala, the
thalamus, the cingulate cortex, the hypothalamus, and septum to name a few. Altered
serotonergic activity has been found in many disorders ranging from ASPD and depression
to anxiety and fibromyalgia.

Endorphins are peptide neuromodulators that when released in the nucleus accumbens
cause a feeling of euphoria, and they are involved in anti-nociception.

Oxytocin is a neuropeptide involved in birth, pair bonding and lactating.

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(2)"Adderall XR Prescribing Information" (PDF). United States Food and Drug

Administration. Shire US Inc. December 2013. pp. 4–8. Retrieved 25 August 2016.

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Neurol.

(9)Le Moal, Michel. "Mesocorticolimbic Dopaminergic Neurons".

Neuropsychopharmacology: The Fifth Generation of Progress. Retrieved 25 August 2016.

(10)Fiorino, DF, Coury, A, Fibiger, HC and Phillips, AG \U0010fc301993) Electrical

stimulation of reward sites in the ventral tegmentum area increases dopamine transmission
in the nucleus acumbers of the rat. Behav. Brain Res.

(11)Schultz, W \U0010fc301997) Dopamine neurons and their role in reward mechanisms.

Curr. Opin. Neurobiol.

(12)Lövheim, Hugo. "A New Three-dimensional Model for Emotions and Monoamine
Neurotransmitters." Researchgate. Elseiver, Dec. 2011. Web. 25 Aug. 2016.

(13)Maia, Tiago V., Rebecca E. Cooney, and Bradley S. Peterson. "The Neural Bases of
Obsessive-Compulsive Disorder in Children and Adults." Development and
Psychopathology. U.S. National Library of Medicine, 2008. Web. 26 Aug. 2016.

(14)Meyer JH, Ginovart N, Boovariwala A, et al. (November 2006). "Elevated monoamine

oxidase a levels in the brain: An explanation for the monoamine imbalance of major
depression". Archives of General Psychiatry.

(15)Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U (March 2012). "Striatal dopamine

transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A
meta-analysis". Am J Psychiatry.

(16)Brisch, Ralf, Arthur Saniotis, Rainer Wolf, Hendrik Bielau, Hans-Gert Bernstein,
Johann Steiner, Bernhard Bogerts, Katharina Braun, Zbigniew Jankowski, Jaliya
Kumaratilake, Maciej Henneberg, and Tomasz Gos. "The Role of Dopamine in
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Still in Vogue." Frontiers in Psychiatry. Frontiers Media S.A., 2014. Web. 26 Aug. 2016.