Mental Disorders and Neurological Disorders

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Mental Disorders and Neurological Disorders

• PY 250

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Schizophrenia

• Most common psychosis afflicts 1 of population
• Positive and negative symptoms
• Positive Symptoms not present in normals
• Thought disorders disorganized thinking
• Hallucinations Auditory, voices talking
• Delusions beliefs contrary to fact

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Schizophrenia

• Negative symptoms Absence of normal behaviors
• Flattened affect
• Poverty of speech
• Lack of initiative
• Inability to experience pleasure

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Five Types of Schizophrenia

• Subtype Symptoms
• Disorganized Disorganized speech, disorganized
  behavior, or inappropriate emotion
• Catatonic Extreme movement symptoms ranging from
  excessive motor activity to posturing
  (immobility for long periods)
• Paranoid Organized cognition and emotion, but
  with hallucinations and delusions that are
  usually concerned with persecution
• Undifferentiated Mixed-bag categorysymptoms fit
  the criteria of more than one of the above
  three types or none of them
• Residual There has been a past schizophrenic
  episode, but presently only some negative
  symptoms and no positive symptoms
  (hallucinations and delusions)

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Type I and Type II

• Another distinction is between Type I and Type
  II schizophrenia
• Type I schizophrenia is characterized by
  positive symptoms
• Type II schizophrenia is characterized by
  negative symptoms
• Type I is more acute, as the person functioned
  normally before the disorder strikes and has a
  better chance of recovery because Type I can
  usually be alleviated with drugs, whereas Type II
  tends to stem from more permanent brain
  abnormalities

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Schizophrenia

• Heritability
• Twin studies
• Adoption studies
• Children of schizo. Have increased chance of
  becoming schizo. independent of whether they
  have been raised by biological parents

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SchizophreniaKety et al., 1958
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Developmental Causes

• One hypothesis involves Neural Developmental
  Abnormalities
• Genes plus abnormalities in prenatal or neonatal
  developmental impair brain development and lead
  to schizophrenia
• linked to poor nutrition in pregnancy, premature
  birth or low birth weight, delivery complications
• Rh-negative mother with Rh-positive baby has
  twice the rate of schizophrenia for second and
  later born boys
• people born in winter have 5-8 higher rate
• may be due to increased likelihood of viral
  infection and fever in mother (1.5 slows
  development of fetal neurons)

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Neurodevelopmental Hypothesis cont.

• Ventricles larger, smaller prefrontal/temporal
  cortex, hippocampus
• fewer than normal synapses in prefrontal cortex
• cell bodies smaller in hippocampus and prefrontal
  cortex
• Brain abnormalities found in young patients are
  no greater in older patients
• but cells may shrink, rather than die, with age
• slow maturation of prefrontal cortex explains
  onset after 20
• Plausible hypothesis but more research is needed

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Schizophrenia Dopamine

• Dopamine (DA) hypothesis
• Positive symptoms may be related to over-activity
  of DA
• DA agonists (amphetamine, cocaine) can produce
  schizo-like symptoms hallucinations, delusions,
  thought disorders
• Drugs that block DA have anti-psychotic efficacy
• best if used early, some fully recover but about
  25 do not benefit from drugs

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Schizophrenia
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Dopamine Hypothesis cont.

• But blocking dopamine receptors doesnt explain
  behavior change weeks later
• General dopamine levels are approximately normal
• but patients have higher number of D2 receptors
  occupied
• and more D2 receptor activation in the prefrontal
  cortex is related to more cognitive impairment

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Glutamate Hypothesis

• An important problem is deficient glutamate
  activity in glutamate synapses, especially the
  prefrontal cortex
• has same effect as increase in dopamine
• dopamine inhibits glutamate and glutamate
  stimulates neurons that inhibit dopamine release
• Persons with schizophrenia release lower amounts
  of glutamate in prefrontal cortex and hippocampus
• also have lower number than normal glutamate
  receptors

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Glutamate Hypothesis cont.

• Phencyclidine (PCP) decreases stimulation of
  glutamate- type NMDA receptors and produces both
  positive and negative symptoms of schizophrenia
• impairs functioning of prefrontal cortex
• induces long-lasting relapse in persons with
  schizophrenia
• Glycine activates cotransmitter site on NMDA
  glutamate receptors that increases the
  effectiveness of glutamate
• also increases the effectiveness of other
  anti-psychotic drugs

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Antipsychotic Drugs

• Block postsynaptic dopamine receptors
• benefits result from effects on the
  mesolimbocortical system, neurons that project
  from the midbrain tegmentum to the limbic system
• however, drugs also block dopamine synapses in
  other locations, e.g., basal ganglia, and produce
  tardive dyskinesia a disorder of tremors and
  involuntary movements
• tardive dyskinesia can last for years after drugs
  are no longer used

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Antipsychotic Drugs cont.

• Atypical antipsychotics, e.g., clozapine, blocks
  D4 receptors but not D2
• does not result in tardive dyskinesia
• beneficial for both positive and negative
  symptoms
• but decreases white blood cells leaving person
  vulnerable to infections

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Neurological Disorders

• Overview
• Tumors
• Seizures
• Cerebrovascular accidents
• Alzheimers Disease

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TumorsCells whose growth is uncontrolled and
which serve no useful purpose
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Tumors

• Malignant Infiltration
• Benign Distinct border
• Tumors do not arise from neurons
• Gliomas From glia Dangerous, fast growing
• Meningioma Cells of meninges
• Pituitary adenoma Hormone secreting cells of
  pituitary
• Angioma Cells of blood vessels

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Seizures

• Sudden excessive activity of cerebral neurons
• Partial seizure Definite limited focus or source
  of irritation
• Generalized seizure Widespread
• Grand Mal includes motor system convulsions
• Auras may precede indicating locus of origin

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Seizures

• Grand Mal Seizure
• Tonic phase arms rigid
• Clonic phase muscles trembling/jerking
• Stuporous sleep

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Seizures

• Petite mal (absences)
• Stare off into space
• Causes of seizures
• Tissue scaring
• Strokes
• High fever
• Treatment
• Anticonvulsants
• Surgery

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EpilepsyRemoving stones from the brain?
Jan Sanders van Hemessen (about 1575)
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Possible causes?
Normal

• Axonal sprouting auto stimulation of network of
  neurons
• Loss of inhibitory K channels and currents
• Bernard et al., 2004

Sprouted
Loss of inhibition
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Cerebrovascular accidents Strokes

• Hemorrhages
• Obstruction (thrombus)
• Produce permanent brain damage
• Therapies
• Clot-busting drugs
• NMDA (glutamate) receptor blockers

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Alzheimers Disease
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Former President Ronald Regan had Alzheimers
Disease
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Alzheimers Disease

• Senile dementia of the Alzheimers type
• Symptoms
• Progressive loss of memory
• Confusion
• Depression
• Restlessness
• Delusions
• Eating disturbances
• Sleep disturbances

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Alzheimers Disease

• Diagnosis confirmed post-mortem
• Tangles and ?-amyloid plaques

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Amyloid Precursor Protein (APP) may be cleaved
into toxic fragments when cut at ß and ? sites
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Aß1-42 protein fragments are exported from cell
and aggregate into tangles and plaques
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Alzheimers Disease

• Possible causes
• Heredity 21st chromosome contains gene that
  produces Amyloid precursor protein (APP) But
  most forms are not hereditary
• Aluminum deposits but Al found in non-damaged
  brain areas
• Excessive alcohol Like Korsakoffs Disease
  (memory loss) ? but different brain areas
  damaged

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Alzheimers Disease

• Possible causes
• Traumatic injury People with closed head injury
  have many ?-amyloid plaques. Contributor?
• Inflammatory disease An immune system reaction?
• People taking anti-inflammatory drugs have low
  rate of ALZ
• Indomethacin enhances cognition in ALZ patients
  (Rogers et al.)