Science Blog: Bipolar Brain

Now as we know there are different types of bipolar:

  • Bipolar I= Categorized by at least one manic episode
  • Bipolar II= Never experiences full blown mania, experiences hypomania
  • Cyclothymia= Mildest form, less severe mood swings between hypomania and mild depression

But how does that relate to the population?

  • Bipolar affects about 2.6% of the U.S population.
  • Bipolar disorder results in 9.2 years reduction in expected life span (scary, right?!)
  • About 1 in 5 patients with bipolar disorder commits suicide.
  • Almost 70% of bipolar patients are misdiagnosed 3 or more times before receiving their correct diagnosis.

Now there is a spectrum for bipolar and here it is:

spectrumAnd we know the symptoms of the spectrum, right?

 Manic Symptoms:

  • Easily distracted
  • Little need for sleep
  • Poor judgment
  • Poor temper control
  • Reckless behavior and lack of self control
  • Elevated mood
  • Easily agitated or irritable
  • Increased energy
  • Racing thoughts
  • Very high self-esteem
  • Talking a lot/quickly
  • Spending sprees
  • Increased promiscuity
  • Poor Judgment
  • Binge eating, drinking, drug use

 Depression Symptoms:

  • Low mood or sadness
  • Trouble concentrating, making decisions, decreased memory
  • Eating problems-weight loss or gain
  • Fatigue
  • Feeling guilty, worthless or hopeless
  • Decreased self-esteem
  • Thoughts of suicide
  • Decreased pleasure in activities once enjoyed
  • Trouble sleeping
  • Isolation from friends and family

Mixed State: When two phases of depression and mania overlap or quickly cycle after another.

But what’s the neurobiology of it all?
ee2These are pictures of bipolar brains. So what does it tell us, well it tells us that:

  • Although the abnormalities in the brain due to bipolar disorder are still unknown, the structural abnormalities believed to be linked to bipolar disorder are amygdala, basal ganglia, and the prefrontal cortex. Research is currently being conducted to find more definite information on the definite causes and changes in the brain of bipolar disorder.
  • Recently using MRI, hyperintense (bright white) spots have been found in bipolar patients. Hyperintensities have previously been associated with a change in water content in the brain tissue, but the causes of these are not known.
  • Amygdala volumes have been shown to be reduced in unmedicated patients and increased in medicated patients. This is seen in the chart below.
    1-s2.0-S1053811909012099-gr2So what does it actually look like, you know, hormonally?
    bipolar-brainAt the top is ‘normal’ brains, in the middle hypomanic and at the bottom depressed brains.

    • Abnormal intracellular function of the brain of bipolar patients, such as producing higher amounts of serotonin, dopamine and norepinephrine.
    • These abnormalities lead to “racing thoughts” or the patient feeling like they can’t “turn off” their brains.
    • In this figure, you can see the reduced activity in the depressed brain, by the presence of more dark blue and can see the overactivity in the manic brain by the presence of more green, yellow and red in the brain scan.

    DanaGuide_CH15C33_P437_spot

    • Studies done with mice have shown that mice with a mutation in the CLOCK gene will develop manic behavior. This behavior includes: hyperactivity, decreased sleep, reduced anxiety, and an increased response to cocaine. The researchers were able to get rid of the manic behavior by returning the expression of CLOCK to normal, specifically in the ventral tegmental area of the mouse brain.
    • The ventral tegmental area is very rich in dopamine receptors. Because of this, the researchers believe that the same issue that the efficacy of atypical antipsychotics in acute mania might be achieved by their ability to lower activity in neurons specifically within the ventral tegmental area.
    • Levels of expression of oligodendrocyte-myelin-related genes are decreased in brain tissue of individuals with bipolar disorder. Oligodendrocytes produce myelin membranes that insulates axons and allow nerve impulses to fire very rapidly, so a loss in myelin is theorized to interrupt the communication between neurons and lead to possible thought disturbances that are seen in bipolar disorder.

    br-800epi1

    -Although individuals with bipolar disorder do not demonstrate a size difference in hippocampus, bipolar patients have shown hippocampal dysfunction in:

    • a reduced volume in nonpyramidal cell layers
    • a reduced number of somatostati-positive and paravalbumin positive neurons
    • reduced somal volume of cornu ammonis sector 2/3
    • reduced mRNA levels for somatostatin, parvalbumin and glutamic acid decarboxylase 1
    • The hippocampal anatomy is displayed above to illustrate these problems.

    Some studies have also shown a loss in gray matter in bipolar patients, depicted in the graph below. Gray matter is made up of neuronal cell bodies and regulates muscle control and sensory perception, which include: seeing, hearing, memory, emotions, and speech.

1-s2.0-S0006322307002338-gr2 003_brain-white-matterOkay, so what CAUSES bipolar disorder?

The causes of bipolar disorder are vastly unknown, and much research is currently being done to determine the exact cause. However, it is believed to be a combination of genetic factors, environmental factors, and the individuals biochemical processes.

–First degree relatives of a person with bipolar disorder are 7 times more likely to develop bipolar disorder.

–80% concordance rate in identical twins and 16% in fraternal twins, which means that in the case of twin studies, an identical twin has an 80% chance of having bipolar if their identical twin has it, and only 16% chance if the twin is fraternal. This explains the high genetic factor seen with bipolar disorder. Because identical twins share 100% of their DNA, while fraternal twins are regular siblings that share only 50% of each other’s DNA.

–Several genes appear to be linked to bipolar disorder:

  • CACNA1C, on chromosome 12. This gene encodes the alpha 1C subunit of the L-type calcium ion channel in the brain
  • ANK3- an adaptor protein found at the axon initial segments and regulates the assembly of voltage-gated sodium channels.
  • Both ANK3 and CACNA1C genes are down-regulated in response to lithium.
  • Abnormal CLOCK gene function

And of course triggers:

  • Stressful life events
  • Certain medications
  • Major life changes
  • Drug or alcohol abuse
  • Seasonal changes
    But these only trigger episodes in predisposed individuals.

Well I’m on the treatment phase now, so what should I expect?

Mood Stabilizers are most often used because although bipolar patients experience depression, antidepressants are used to treat bipolar patients with caution, because antidepressants have been known to trigger manic episodes in individuals with bipolar disorder. If antidepressants are used, they are used in addition to mood stabilizing drugs.

  • Lithium
  • Valproate
  • Lamotrigine
  • Carbamazephine

ECT: Electroconvulsive therapy (ECT) may be used to treat the manic or depressive phase of bipolar. ECT uses an electrical current to cause brief seizure, while the individual is under anesthesia. This is considered the most effective non-drug treatment for bipolar disorder.

Transcranial magnetic stimulation (TMS) uses high-frequency magnetic pulses to target affected areas of the brain. This treatment if used more commonly than ECT.

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2 thoughts on “Science Blog: Bipolar Brain

  1. Hello,
    This was very interesting and helpful. I am Bipolar Type I rapid-cycler. Do you have any scientific information about rapid-cycling? Every 90 days, I feel a cycle, whether leading to hypomania or to depression, but they are normally managed by my psycho-pharmaceuticals. I am just recovering from a severe depressive cycle. A few years ago, I had an MRI while I was in a serious depression and having some fine motor skill difficulties and sensory disruptions. The doctors said that my brain looked similar to that of First Stage Alzheimer’s patients. Do you have any indications of this within your scientific repertoire?
    Thanks for posting. This is very interesting and information that I feel every Bipolar patient should understand.

    • I will write blog about it in the next few days and be sure to let you know I’ve made it.

      I will also see if I can find anything like having an MRI and your brain looking similar to Alzheimer’s patients.

      You are very welcome, take care of yourself.

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