NANCY LONG SIEBER, PH.D.SEPT. 13, 2010

A bit about lupus and then

Neuropathophysiology I

http://www.medicinenet.com/images/illustrations/butterfly_rash.jpg

http://www.naturosante.ch/B.L.-lupus-evolution-1.jpg

The arrow labeled "axon" is pointing directly at the initial segment.

http://medlibrary.org/medwiki/Axon_hillock

EPSPs and IPSPs are integrated at a site at the base of the axon called the initial segment

(also known as the axon hillock).

Major Neurotransmitters Involved in Mood Regulation

• Norepinephrine

• Serotonin

• Dopamine

Depression

http://www.drugdevelopment-technology.com/projects/rasagiline/rasagiline1.html

Drugs that treat depression• Monoamine oxidase inhibitors (MAOIs) – block the enzyme that breaks

down norepinephrine and serotonin

• Selective serotonin reuptake inhibitors (SSRIs) – block reuptake of serotonin by the presynaptic neuron. Eg: Prozac

• Serotonin-Norepinephrine reuptake inhibitors – block reuptake of both serotonin and norepinephrine. Some also block dopamine reuptake. Eg: Wellbutrin

•

While studying modern antidepressant drugs, researchers identified a treatment

that worked 75% as well as the drugs under consideration, with no side effects.

It was the placebo.

The placebo effect is greatest on conditions that respond to the body’s own biochemicals, such as

endogenous opioids and dopamine.

Placebos sometimes work for:

• Hypertension • Pain • Parkinson’s disease • Psoriasis • Rheumatoid arthritis • Ulcers

Placebos do not work for:

• Atherosclerosis • Cancer • Growth-hormone deficiency • High cholesterol • Infertility • Obsessive-compulsive disorder

Newsweek 2/8/10 Sharon Begley “The Placebo Effect”

Current thoughts on antidepressants

• Antidepressants appear to be most effective for severe depression and chronic mild depression

• In mild to moderate depression, it is difficult to distinguish between drug effect and placebo effect.

• Drugs work best when combined with psychotherapy.

Bipolar Disorder

Characterized by over activity of the amygdala and under activity of the prefrontal cortex

http://cwx.prenhall.com/bookbind/pubbooks/morris5/medialib/images/F02_09.jpg

Diagnosed with bipolar disorder and attention deficit disorder at age 2.

Died at age 4 of an overdose of prescription drugs used to treat these conditions.

Is it better to diagnose and treat these conditions early, or is the risk of over-diagnosing and over-treating too great?

How can we assure that parents don’t misuse these powerful drugs?

Rebecca Riley

How common is bipolar in children?

Dopamine

• Parkinson’s disease is associated with a loss of dopamine-producing neurons in the basal ganglia, which is involved in movement.

• Schizophrenia is associated with an excess of dopaminergic transmission.

The art of Louis Wain (1860-1939)

Throughout his career, Wain painted pictures of cats.

At the age of 57, Wain developed schizophrenia.

The disease is

reflected in his art:

Dopamine also helps regulate mood.

• Central to our feeling of pleasure and reward.

• Dopamine is also associated with motivation and memory.

• Addictive drugs and behaviors involve dopamine pathways.

Drugs and Dopamine• All addictions are thought to involve dopamine – it

provides the drive to repeat pleasurable behaviors eg: smoking, drinking, shopping, etc.

• Some drugs directly alter dopamine neurotransmission– Methamphetamine causes the release of large amounts of

dopamine– Cocaine blocks reuptake of dopamine at the synapse

Methamphetamine use affects the entire body

http://factoidz.com/methamphetamine-and-the-damage-it-does/

Cocaine blocks dopamine reuptake – results in feelings of euphoria

http://www.nida.nih.gov/NIDA_Notes/NNVol13N2/brain.gif

Dopamine and Addiction

Dopamine is made in the ventral tegmental area (VTA), and is released in the nucleus accumbens, the pleasure center.

Methamphetamine use causes permanent damage to the brain

http://www.nida.nih.gov/NIDA_Notes/NNVol15N4/Methamphetamine.html

How to treat addiction?• Detoxification – safely withdraw from drug

• Rehabilitation – slow process of dealing with psychological as well as physical addiction

• Medications used:– Safer forms of drugs that act on the same receptors

as the drug of abuse. Eg: nicotine patch, methadone– Drugs that block the effect of drug, or that cause

illness if drug is used. Eg: Antabuse for alcohol.– Certain antidepressants also help. Eg: Wellbutrin

Alcohol Consumption Per Capita

Source: World Health Organization

How to treat addiction?

• Detoxification – safely withdraw from drug

• Rehabilitation – slow process of dealing with psychological as well as physical addiction.

• Medications used:– Safer forms of drugs that act on the same receptors

as the drug of abuse. Eg: nicotine patch, methadone– Drugs that block the effect of drug, or that cause

illness if drug is used. Eg: Antabuse for alcohol.– Certain antidepressants also help. Eg: Wellbutrin

Major Neurotransmitters

Small MoleculesNeuropeptides

AcetylcholineNitric OxideBiogenic AminesEpinephrineNorepineprineDopamineSerotoninHistamineAmino AcidsGlutamateAminobutyric Acid (GABA)GlycineAspartateHomocysteineTaurineNucleotidesAdenosineAdenosine triphosphate

Hypothalamic Releasing HormonesCorticotrophic Releasing Hormone

Growth Hormone Releasing HormoneThyrotrophin Releasing Hormone

Pituitary Peptidesß endorphins

OxytoxinVasopressin

Adrenocorticotropic Hormone (ACTH)Thyroid Stimulating Hormone (TSH)

Growth HormoneGastrointestinal Peptides

SecretinSubstance P

InsulinGastrin

NeurotensinSomatostatin

CholecystokininOthers

AngiotensinBradykinin

Neuropeptide YCalcitonin