disorder study guide

Major Depressive Disorder

• Periods of two or more weeks of a depressed state.

• Includes gaining less pleasure from things that would normally give pleasure.

  • Known as anhedonia.

Genetics & MDD

• Concordance rate for identical twins is around 50%.

  • Adoption studies support a role for genetics.

• Depression seems to be related to anxiety disorders.

  • Families that have depressed members also tend to have higher rates of anxiety disorders.

Structural Issues of MDD

• Positive emotions have been linked to the left frontal lobes.

• Depression is correlated with increased right frontal lobe activity and decreased frontal lobe activity.

• People with left hemisphere damage from a stroke are more likely to develop depression than those with right hemisphere damage.

  • However, correlational does not equal causation.

  • It may be due to a loss of other functions.

Limbic Irregularities in MDD

• Depressed people exhibit increased activity in brain regions associated with negative emotions, such as the amygdala and anterior cingulate cortex.

• They also have less activity in brain areas linked to positive emotions, such as the prefrontal cortex.

Chemical Issues with MDD

• Abnormal levels of chemicals.

  • Some neurotransmitter deficiencies may be a result of other neurotransmitter deficiencies.

• Elevated growth hormone, thyroid hormone, cortisol, glucocorticoids.

• Lowered monoamines.

• HPA axis irregularities.

Sleep Irregularities & MDD

• Fall asleep faster.

• Enter REM earlier.

• Spend less time in stages 3 and 4.

• Awaken frequently.

Monoamine Theory of Depression

• Depressed people have monoamine deficiencies.

• Drugs that decrease monoamines can cause depression.

  • E.g., reserpine (used to lower blood pressure).

• Drugs that increase monoamines help with depressive symptoms.

• Monoamines associated with depression include serotonin, norepinephrine, and dopamine.

Issues with the Monoamine Theory

• It minimizes the contribution of other neurotransmitters.

  • Glutamate and GABA are the two most common neurotransmitters in the CNS.

  • One would think they might be involved.

• Drugs that increase the amount of monoamines typically take weeks to help improve symptoms.

  • Led to a new focus on the receptors.

  • Receptor Sensitivity Theory

  • It’s long-term changes at the receptors that help depressed patients improve.

Bipolar Disorder

• Alternating periods of depression and manic states.

• Concordance rates of 70-90%.

Brain Structures & Bipolar Disorder

• Lower amount of grey matter in the prefrontal cortex and limbic structures.

• Basal ganglia function abnormalities.

  • The striatum is a key structure of the basal ganglia that helps with executive functions.

Chemical Issues with Bipolar Disorder

• Thought to be monoamine-related since depression is a component of bipolar disorder.

• If depression = too little monoamine.

  • Mania could be too much monoamine.

• There may be an imbalance.

  • Too little serotonin and too much norepinephrine.

Schizophrenia

• Positive (adding) symptoms:

  • Delusions, hallucinations, disorganized speech, disorganized behavior.

• Negative (taking) symptoms:

  • Social withdrawal and mood disturbance.

• Activity pattern for a hallucination lacks the activity in the basic auditory structures.

Genetics & Schizophrenia

• Heritability index of 40-60%

• Fraternal twins have a 10-20% concordance rate.

• Children of a schizophrenic patient have a 14-17% chance.

Structural Issues of Schizophrenia

• Tissue loss in the frontal cortex, anterior temporal lobes, and the hypothalamus.

• Enlarged ventricles and a shrunken hippocampus.

• Hippocampus cell bodies in a schizophrenia patient appear disorganized.

  • Hippocampus cell bodies in a control participant are arranged neatly.

Chemical Issues in Schizophrenia

• Dopamine hypothesis.

• Overabundance of dopamine leads to overactivity.

• May be the basis for hallucinations and delusions.

Anxiety Disorder

• A mutation in the SERT gene is linked to low serotonin levels.

  • Serotonin transporter gene.

  • Also linked to an increase in anxiety disorders.

  • SERT regulates levels of serotonin.

• CRH1 gene

  • Linked to corticotropin-releasing hormone.

  • Impacts the HPA axis, which triggers cortisol release.

Panic Disorder

• Stimulants can initiate an attack in a patient with panic disorder, probably by stimulating the locus coeruleus.

• Antidepressants effective in panic disorder reduce activity in the locus coeruleus.

• A circuit connecting the hippocampus, orbitofrontal cortex, and cingulate gyrus may mediate panic attacks.

OCD

• Repetitive, intrusive thoughts accompanied by ritualistic, repetitive behaviors.

• Concordance rate of 68%.

• Birth trauma, infection, and injury may also cause OCD.

• Abnormal activity in the basal ganglia, prefrontal cortex, orbitofrontal cortex, cingulate gyrus.

Alzheimer’s Disease

• A progressive neurodegenerative disorder and most common cause of dementia, characterized by memory loss, impaired reasoning, language difficulties, and disorientation.

• Could have vascular causes (strokes).

• Parkinson’s and Huntington’s disease lead to dementia.

• Infections of the brain can lead to dementia.

• Alzheimer’s is strictly neurological and associated with aging.

Structural Problems of Alzheimer’s Disease

• Shrinkage of the hippocampus by up to 40% as well as the temporal and parietal lobes.

Baptists

• Believe beta-amyloid plaques lead to Alzheimer's disease.

  • Usually surrounded by clumps of degenerating axons and glial cells, which means they must be toxic.

• Beta amyloid is derived from Beta amyloid precursor protein.

  • When BAPP is broken down in normal patients, it is cut into pieces, one of which has 40 amino acids.

  • Alzheimer’s patients get a cut strand with 42 amino acids, which appears to be toxic.

• Problem: levels of this toxic strand of protein do not correlate with the severity of dementia in Alzheimer’s patients.

Taurists

• Believe neurofibrillary tangles lead to Alzheimer’s disease.

• Neurofibrillary tangles are made from the protein tau.

• They are found throughout the hippocampus and cerebral cortex.

Chemicals & Alzheimer’s Disease

• Acetylcholine is the main neurotransmitter thought to be linked to Alzheimer’s.

• Levels of Ach have never been able to be measured.

• Choline acetyltransferase is involved in the synthesis of Ach, reducing levels up to 90%.

• Leads to the most common treatment:

  • Cholinesterase inhibitors stop the breakdown of Ach.

Genetics & Alzheimer’s Disease

• 4 main genes to know.

• Down syndrome patients have higher levels of Alzheimer’s.

  • Led to the search for Alzheimer’s disease gene.

    • Chromosome 21

    • APP gene

• Presinilin genes

  • Chromosomes 1 and 14

• All above genes lead to more of the 42-AA strand protein.

• All linked to early onset of Alzheimer’s.

Late-Onset Alzheimer’s Disease

• ApoE gene

  • Chromosome 19

  • Comes in 3 possible forms: ApoE-2, ApoE-3, ApoE-4

  • Mean age of onset for Alzheimer’s

    • Patients who inherit two Apoe-2 genes: over 100 years.

    • Patients who inherit two ApoE-3 genes: 80-90 years.

    • Patients who inherit two ApoE-4 genes: under 70 years.

Parkinson’s Disease

• Difficulty moving

• Tremor in resting body parts

• Frozen facial expressions

• Stooped posture

• Loss of balance, frequent falls

• Autonomic disturbances

• Dementia in later stages

• Premature death

Structural Brain Problems & Parkinson’s Disease

• Degeneration of substantia nigra (midbrain)

• Damage to the basal ganglia

Chemical Issues & Parkinson’s Disease

• Dopamine levels are 40% of normal.

• Proposed treatment: L-DOPA, a precursor to dopamine.

  • Leads to an increase in dopaminergic activity throughout the body.

  • Benefit: increases in dopamine levels in the basal ganglia lead to a decrease in Parkinson’s symptoms.

  • Cost: Harmful side effects:

    • Increases dopamine levels throughout the body, leading to issues with the liver and other organs.

    • Only treats the symptoms, not the cause.

• Noradrenaline, serotonin, and acetylcholine levels have been found to be lower in Parkinson’s patients.

Genetics of Parkinson’s Disease

• Strongly linked to early-onset Parkinson’s.

  • Alpha-synuclein protein is tweaked.

    • One guanine is changed to adenine.

Treatment for Parkinson’s Disease

• Stem cells

• Deep brain stimulation

Huntington’s Disease

• Produces involuntary, jerky movements, depression, hallucination, delusions.

Structural Problems of Huntington’s Disease

• General shrinkage of the brain by up to 20%.

• Striatum degeneration (basal ganglia)

  • Up to 95% of cells degenerated at the time of death.

Chemical Issues & Huntington’s Disease

• Lower levels of GABA and acetylcholine

• Higher dopamine levels, possibly due to the loss of GABA because it’s inhibitory.

• Possibly too much glutamate.

  • When injected into the striatum, glutamate produced HD-like symptoms.

  • Possibly due to calcium levels increasing.

Genetics of Huntington’s Disease

• Heritable condition

• Autosomal dominance

  • Parents with Huntington’s pass it on 50% of the time.

  • The disease does not develop until middle age.

• Antibiotics, fetal tissue transplants, and maintaining activity may provide treatment in the future.

Antidepressants

• Monoamine theory led to current medications.

• Monoamine Oxidase Inhibitors (MAOIs)

  • MAOIs suppress MAO, which breaks down monoamines.

  • Cause harmful side effects and dangerous dietary restrictions.

• Tricyclic antidepressants

  • Contains a 3-ring carbon chain.

  • Inhibits the reuptake of serotonin and norepinephrine.

  • Also acts on histamine and acetylcholine.

  • Leads to side effects.

  • Led to the desire to develop drugs that worked in very targeted ways.

• Selective serotonin reuptake inhibitors (SSRIs)

  • Inhibits the reuptake of serotonin.

  • Prozac, Zoloft, Lexapro.

  • Response rate is no better than for Tricyclics, but fewer side effects and health concerns.

• Other medications being researched:

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)

  • Norepinephrine-dopamine reuptake inhibitors (NDRIs)

Dopamine Hypothesis

• Evidence in favor:

  • Drugs that increase dopamine activity in schizophrenics increase symptoms.

  • Drugs that block dopamine receptors lessen symptoms.

• Evidence against:

  • 25% of patients don’t respond to dopamine antagonists.

  • New generations of antipsychotic meds impact other neurotransmitters beyond just dopamine.

  • Drugs change dopamine activity immediately, but patients may not improve for weeks.

  • Dopamine inhibits prolactin production, but prolactin levels in schizophrenics are normal.

  • PCP leads to schizophrenia like symptoms by blocking the NMDA (glutamate) receptor.

Adjustments to Chemical Theories

• Revised dopamine hypothesis:

  • Increase dopamine activity in mesolimbic areas (reward pathway) and decrease dopamine activity in the prefrontal cortex.

• Glutamate hypothesis:

  • Glutamate levels may explain the negative symptoms better than dopamine.

Treatments for Schizophrenia

• Antipsychotic medication blocks dopamine.

  • Thorazine.

  • May lead to tardive dyskinesia (drug-induced version of Parkinson’s).

• New generation antipsychotic medication blocks serotonin and dopamine.

  • Clozapine.

  • Works on 30-50% of patients for whom Thorazine didn’t work.

• TMS can help reduce hallucinations.

  • TMS is a non-invasive treatment that uses magnetic fields to stimulate nerve cells in the brain.

Transmissible Spongiform Encephalopathies

• Psychological disturbances:

  • Paranoia, anxiety, depression

• Progressive loss of cognition

• Motor disturbances

• Death

Types of TSEs

• Scrapie (sheep)

• Bovine spongiform encephalopathy (BSE or mad cow disease) (cattle)

• Creutzfeldt-Jakob disease (humans)

• Kuru (humans)

• New variant Creutzfeldt-Jakob disease (humans)

Causes of TSEs

• TSE infectious agents differ from viruses:

  • Long incubation period, lack of inflammation, immunity to hospital sterilization techniques.

• Prusiner isolated abnormal proteins called prions.

• Prions are proteins encoded by genes.

  • Uninfected animals encode the protein, but if they have TSE, the protein is folded differently.

  • Can be genetically inherited or incorporated through the digestion of the abnormal protein.