Neuroscience 210

  1. Schizophrenia (general)
    • - normal mental processes like sensation, perception, language, emotion, relationships go awry
    • - affects more than just the person, also friends and family
    • - economic burden
    • -----1.5 billion dollars in direct health care and non health care costs , and another 1.5 bill in lost productivity and morbidity/mortality (total cost of morbidity 52%, higher than hospitalization 24%)
  2. Psychosis
    • •“Psychosis” --refers to mental disorders in which there is a loss of contact with reality
    • •Psychosis affects the ability to think, feel and act
    • •Most people with psychosis are aware of and distressed by their experiences
    • •The term “psychotic disorders” is used to describe a range of mental disorders that all involve symptoms of psychosis
    • •Non-affective psychotic disorders are among the most serious of all mental disorders and have been referred to as “Youth’s greatest disabler” because of the early age of onset
    • •Can be lifelong conditions which require optimal care from the onset and can be effectively treated
  3. Prevalence of psychotic disorders
    • •Psychotic disorders are more common than many people realize
    • –Approximately 3 out of every 100 people will experience some type of psychosis (affective and non-affective) during their lifetime
    • –Approximately 1 out of every 100 people will be diagnosed with schizophrenia during their lifetime
  4. incidence
    •No. of new cases (however defined) in a specified time period

    •Studies have usually reported treated incidence rates

    •Range 0.30/1,000 to 1.2/1,000

    • •Incidence rates higher for males than females between ages of 15-34
    • - mean age at first episode is about 21 for men and 26 for women
    • - incidence rate peaks between ages 15-24 for men, 25-34 for women who also have a smaller peak in their 40's
    • -
    • –Total lifetime risk does not differ significantly by sex
  5. Phases
    • Birth-->premorbid phase
    • first signs of ilness --> prodomal
    • Onset of illness--> duriation of untrated psychosis (if longer, more severe chronic illness)
    • First treatment-->time to response
    • residual symptoms--> residual phase
    • Chronicity/treatment-resistence relapse phase
  6. Developmental cascade towards schizophrenia
    Subtle motor, cognitive and social deficits during infancy can be caused by obsetric events, (neuregulin, dysbinding, DISC 1)

    Social anxiety, quasi psychotic ideas, depression--in later years (around 10)--brought out by chronic social adversity

    Neurotransmitter genes like COMT (turn into enzymes that modify receptors and NT activities) and drug abuse can bring about dopamine dysregulation which can lead to the onset of psychosis

    omega 3 can prevent transition from promodromal phase to schizo
  7. Prodromal symptoms in first episode of psychosis
  8. •Reduced concentration, attention
    • •Reduced drive and motivation, anergia
    • •Depressed mood
    • •Sleep disturbance
    • •Anxiety
    • •Social withdrawal
    • •Deterioration of role functioning
    • •Irritability
  9. Core symptom clusters
    • •Positive symptoms
    • •Negative symptoms
    • •Mood symptoms
    • •Disorganization symptoms
    • •Cognitive deficits
  10. Positive symptoms
    • •Delusions --e.g. dwite didnt trust anyone
    • -persecutory, religious, grandoise, somatic

    • •Thought disorder --dwite had disorganized thoughts
    • - loosening of assocations, derailment, incoherence, stereotypical thinking, echolalia, concretemess (fixating on one topic)

    • •Hallucinations ---dwite thought he was the devil and that he heard voices
    • - auditory (most common), visual (rarely occur alone), tactile, olfactory, gustatory, cenesthetic (abnormal bodily sensations which can have no anatomical basis)

    •Bizarre behaviour

  11. Negative symptoms --->5 a's
    • •Affective flattening –Reduced or absent facial emotional expression e.g. dwite had a mask like face, no emotion in his voice etc
    • •Alogia –Poverty of thought content e.g. Dwite didn't ask many questions
    • •Avolition –Lack of initiative and motivation
    • •Apathy
    • •Anhedonia –Lack of interest
    • •Emotional and passive social withdrawal
  12. Mood disturbances
    • •Feeling strange; feeling that things don’t seem real
    • •Irritability
    • •Anger
    • •Dysphoria, anxiety
    • •Inappropriate affect
    • •Depression
    • •Excitement
    • •Mood swings
  13. Disorganization symptoms
    disorganized behaviour and thinking
  14. Cognitive deficits
    Kraepelin's dementia praecox--core feature--> early dementia, sudden change in being able to express self

    • •Studies have demonstrated presence of cognitive deficits prior to onset of illness
    • •Cross-sectional studies have shown that cognitive deficits in subgroup of first episode psychosis patients may be as severe as those seen in more chronic patients
    • •Drop of 10 I.Q. points from premorbid level --chaotic mental state makes it difficult to take test

    • Main things affected:
    • –Frontal cortex functions -->executive functions e.g. problem solving, planning, judgment
    • –Attention, concentration and information processing
    • –Verbal memory
  15. Diagnosis
    • •Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): (criterion A--active phase symptoms)
    • 1.Delusions
    • 2.Hallucinations
    • 3. Disorganized speech
    • 4. Grossly disorganized or catatonic behaviour
    • 5. Negative symptoms (i.e. affective flattening, alogia or avolition)

    • Only 1 Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice
    • keeping a running commentary on the person’s behaviour or thoughts, or 2 or more voices are conversing with each other

    •For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement)
  16. Duration
    • •Continuous signs of the disturbance persist for at least 6 months.
    • • 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meets Criterion A (i.e. active-phase symptoms)
    • • May include periods of prodromal or residual symptoms.
    • –Only negative symptoms or 2 or more symptoms listed in Criterion A present in a reduced form (e.g. odd beliefs, unusual perceptual experiences).
  17. Exclusion of schizoaffective and mood disorders in the diagnosis
    • •Schizoaffective and mood disorder with psychotic features have been ruled out because either:
    • –1. No Major depressive, manic , or mixed episodes have occurred concurrently with the active phase symptoms; or
    • –2. If mood episodes have occurred during active phase symptoms, their total duration has been brief relative to the duration of the active and residual periods.
  18. exclusion of sustance/general medical condition exclusion in diagnosis of schizo
    •The disturbance is not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition

    • •If there is a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated)
  19. course and outcome
    outcome with the patient at the center, and family, rehab services, mental health and community support services around it

    • look at things like :
    • Symptoms Quality of life
    • Cognitive function Relapse/Hospitalization
    • APD-Side effects Family burden
    • Social function Compliance
    • Independent living Cost of illness/treatment
    • Vocational functioning Societal impact
  20. Prognosis
    • suicide is a problem 25-40 % attempt, 12% success rate
    • both men and women try the same, but females with schizo have 18 times greater risk compared to general population, men 10X

    significant impairments in most, moderate symptoms in a lot, good prognosis in about 1/4
  21. Predictors of poor outcome
    • •Duration of untreated psychosis (DUP) is the single factor most strongly correlated with outcome
    • –Poorer outcome correlated with longer DUP

    • •Age of onset
    • –Earlier age of onset associated with poorer outcomeFamily history
    • –Genetic vulnerability

    • •Gender
    • –Males tend to have poorer outcome
    • – Protective role of Estrogen?

    • •Neurodevelopmental abnormalities
    • –Obstetrical complications, perinatal injury
    • –Pre-existing movement disorder or soft neurological signs
    • –Structural brain abnormalities

    • •Prominent negative symptoms –“Deficit syndrome”
    • •Cognitive deficits –Verbal memory; attention; executive function
    • •Persistent positive symptoms
    • •Substance abuse
  22. goals of treatment
    • •Efficacy against positive and negative psychotic symptoms and comorbid cognitive and mood symptoms
    • •Minimize side effects
    • •Enhancement of patient compliance/tolerance
    • •Prevention of relapse
    • •Improvement in social functioning
    • •Improved quality of life and hope for reintegration
  23. Dopamine involvement
    use antipsychotics to block D2 receptors in each path way

    • Four pathways:
    • 1.Nigrostriatal --cause EPRs--parkinsons side effects
    • 2.Mesolimbic --causes relief of psychosis
    • 3.Mesocortical --increases negative symptoms
    • 4.Tuberoinfundibular--increases prolactin levels, causes sexual dysfunction
  24. Typical vs Atypical
    • •Typical Antipsychotics: e.g. haloperidol, chlroromazine, pimozide, flupenthixol, fluphenazine
    • --conventional, 1st generation, typically cause abnormal involuntary movements

    • •Atypical Antipsychotics: Clozapine, Olanzapine, Quetiapine , Risperidone, Ziprasidone , Aripiprazole
    • - nonconventional, 2nd generation--typically don`t cause EPRs but have metabolic side effects
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Neuroscience 210