PSYC 10: Schizophrenia PATHOPHYSIOLOGY

1) Lifetime prevalence of schizophrenia

2) Is the mean age of onset later in males or females

3) Suicide rate

4) ____% of patients are smokers

5) Lifespan of an individual w/ schizophrenia is _____ than the general population

1) 1.0%

2) Females

3) 10-15%

4) 75%

5) 10 years less

1) What is risperidone metabolized by

2) What is risperidone metabolized to

1) CYP-2D6

2) Paliperidone (9-hydroxy)

Mesolimbic Dopamine Pathway

1) Projects from ______ to the _______

2) What is this pathway associated with

3) What can INCREASED dopamine in this pathway lead to

4) How are antipsychotics associate w/ this pathway / the goal of using antipsythocitcs in this pathway

1) Ventral Tegmental Area (VTA) to the Limbic system

2) Positive symptoms

3) Psychosis

4) Antagonizers (block) D2 receptors = less DA = decrease (+) symptoms

• DECREASE dopamine to decrease positive symptoms

Dopamine Hypothesis of Schizophrenia

1+2) Hypothesis evolved from what two observations (2)

3) What does this hypothesis NOT explain

4) Does the theory elaborate on what aspect of DA? (Too much release, too much dopamine, too many receptors, hypersensitivity)

1. Antipsychotics treat psychosis (by blocking D2 in mesolimbic)

2. Amphetamines and cocaine (which INCREASE DA) can mimic paranoid schizophrenia

3. DOES NOT explain (-) symptoms of schizophrenia

4. NO, probably a combo of everything

Mesocortical Dopamine Pathway

1) Projects from __________ area of brainstem to the _______

2) Some areas of this pathway regulate ____, _____, _____ (3)

3) Too ____ dopamine in this pathway leads to _____ _______

4) The GOAL w/ antipsychotics is to ____ dopamine in this pathway

1) Ventral Tegmental Area (TGA) to the prefrontal cortex

2) Cognition, executive function, emotions + affect

3) LITTLE dopamine leads to NEGATIVE SYMPTOMS

4) INCREASE

Nigrostriatal Dopamine Pathway

1) Projects from ______ to the ______ or _____

2) Decrease dopamine in this pathway causes _____

3) Chronic antagonism (blockade) of D2 receptors in this pathway can result in _____

4) Parkinsonism occurs when you block >___% of D2 receptors in the ____ pathway

1) Substantia nigra to the basal ganglia or striatum

2) Movement disorders (Parkinsonism)

3) Tardive dyskinesia (can be irreversible)

4) 80% in the mesolimbic pathway

Tuberoinfundibular Dopamine Pathway

1) Projects from _____ to the _____

2) Increased levels of dopamine leads to ____ prolactin which is (good/bad)

3) Decreased levels of dopamine leads to _____ prolactin which is (good/bad)

4) Therefore, you want dopamine ____ in this pathway

5) Symptoms associated with elevated prolactin

1) Hypothalamus to anterior pituitary

2) Increased DA = Decreased prolactin = good

3) Decreased DA = Increased prolactin = bad

4) Increased release in this pathway is the want (inverse relationship)

5)

• Galactorrhea

• Amenorrhea

• Sexual dysfunction

• Reduced bone density

• Infertility

• Osteopenia

• Acne

DSM-5 Criteria for Schizophrenia

1) ___ or more of the following for at least __ ___ with at least ___ ___ of active symptoms (+ what’s one way of remembering this)

2) At least 1 diagnostic symptom MUST BE one of ____ , ____ , ____ (3)

3) The other diagnostic symptoms include: (2)

4) Does social functioning need to be affected for diagnosis?

5) What things do you need to rule out? (4)

1) 2 or more; 6 months; 1 month active symptoms

2) Must be one of:

• Delusions

• Hallucinations

• Disorganized speech

3) Other diagnostic symptoms can include:

• Grossly disorganized / catatonic behaviour

• Negative symptoms (alogia, anhedonia, etc)

4) Yes

5) Schizoaffective disorder, mood disorder, substance use, medical condition

1) How do you treat catatonic behaviour

2) What are some examples of catatonic behaviour (6)

1) High dose BZD

2) Types:

• Not responding to people/environment

• Not speaking

• Holding their body in unusual positions

• Resisting people who try and adjust their body

• Agitation

• Repetitive, seemingly meaningless movement

Positive symptoms of schizophrenia (mesolimbic system)

1. Hallucinations

2. Delusions

3. Disorganized speech

4. Catatonic behaviour

5. Thought disorder characterized by:

   1. Loose associations

   2. Tangentiality

   3. Incoherent thoughts

   4. Neologisms

   5. Thought blocking

   6. Thought insertion

   7. Thought broadcasting

   8. Ideas of reference

Negative symptoms of schizophrenia (mesocortical pathway) (6)

• Alogia (Poverty of speech)

• Anhedonia

• Affective flattening (minimal emotion)

• Avolition (loss of motivation)

• Attentional deficits

• Asociality

What is tangentiality

Positive symptom (thought disorder)

• Tendency to speak about topics unrelated to the main topic of discussion

**Differs from loose assocations

What is neologisms

Positive symptoms (thought disorder)

• Made up their own language/speech

• Newly coined word/expression

Affective Symptoms

1) What part of brain

2) Examples

1) Ventromedial prefrontal cortex

2) Types:

• Depressed mood

• Anxious nood

• Guilt

• Tension

• Irritability

• Frequent worry

Aggressive Symptoms

1) What part of brain (2)

2) Types

1) Orbitofrontal cortex (“odd”), + amygdala (stores memory of fear)

2) Types:

• Impulsive control

• Verbal / physical abusiveness

• Frank violence (assault)

• Self injurious behaviours (includes suicide)

Cognitive Impairment

1) Where in the brain

2) Examples

1) Dorsolateral prefrontal cortex

2) Examples:

• Problems maintaining goals

• Problems with attention

• Problems prioritizing

• Problems modulating behaviour

• Problems with learning

• Impaired verbal fluency

• Difficulty with problem solving

• Problems with memory

COURSE AND PROGNOSIS:

1) Typically symptoms begin at _____

2) Onset can be due to _____ _____ or _____

3) _______ _____ may last a year before onset of overt psychotic symptoms

4) Only ____% do not relapse

5) What does each relapse cause

6) Which symptoms become less severe with time

7) Which symptoms are harder to treat / increase in severity over time

1) Adolescence

2) Environmental changes or substance use

3) Prodromal syndrome

4) 11%

5) Further deterioration in patient’s baseline functioning

6) Positive symptoms

7) Negative symptoms

Which pathways are

1) Hyperactive in schizophrenia

2) Hypoactive in schizophrenia

4) Normal in schizophrenia

PRIOR TO TREATMENT W ANTIPSYCHOTICS

1) Mesolimbic

2) Mesocortical

4) Nigrostriatal, tuberoinfundibular

1) You want to aim to block ____% of DA receptors in mesolimbic pathway to treat psychosis

1) 60-75%