PSYC 301 Final - Dysfunction Associated with Psychiatric Disorders 2

Schizophrenia

What is the DSM-5 criteria for Schizophrenia?

1. 2+ for a 1-month period (must include one of a,b,c):

   a) Delusions

   b) Hallucinations

   c) Disorganized Speech (derailment/incoherence)

   d) Grossly disorganized/catatonic behaviour (agitation/movements without purpose)

   e) Negative symptoms (ex. lack of emotion/expression/motivation)

2. Level of functioning in 1+major areas, such as work/interpersonal relations/self-care is sig. below level prior to the onset (or if onset is in childhood/adolescence, failure to achieve expected level of interpersonal, academic, or occupational functioning)

3. Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms

4. Schizoaffective disorders (bipolar I, depression with mania) have been ruled out

5. Disturbance not attributable to the physiological effects of substances

   (e.g., a drug of abuse, a medication) or another medical condition

What are the 3 symptom of schizophrenia categories?

• Positive Categories

• Negative Categories

• Cognitive Abnormalities/Disorganization Symptoms

Positive Symptoms

Mental phenomena that do not occur in healthy people 

• Hallucinations: Perceptions without sensory cause 

  • Often auditory (ex. voices, noises)

  • Commands hallucinations have a high risk of harm (ex. suicide), not found in all people with schizophrenia 

• Delusions: Beliefs that are not realistic/culturally appropriate 

  • Can be quite varied + bizarre 

  • “The world is full of hidden signs for me, i am being closely watched, other people know my thoughts”

Negative Symptoms

Resulting from an impairment of normal function

• Blunted emotional responses (“affective flattening”) 

• Impoverished content of thought and speech (disturbed attention) 

• Reduced social motivation

Cognitive Abnormalities

• Impaired working memory and executive function (ability to choose appropriate actions + inhibit inappropriate ones) 

• Impaired source monitoring 

  • Tendency to misattribute own actions and thoughts to external causes

  • Errors confusing imagination and real memory 

• Genetic predisposition

How is schizophrenic speech categorized?

• Grammar intact, content is incoherent/”wanders” 

• “Loosening of associations”, connections between thoughts are loose

What is the role of genetics and schizophrenia?

• Large genetic contribution! Risk with an affected family member 

• Higher degree of relatedness = more likely to develop (ex. Twins most likely, not related/first cousin is least likely) 

• ~0.5-1.5 of population diagnosed with schizophrenia

• Slightly more common in men 

• Onset usually teens - early 30s

• Often preceded by prodromal period (some symptoms surfacing, ex. Some social changes or odd beliefs), but not a guarantee for diagnosis

What are some risk factors for Schizophrenia?

• Genetics 

• Urban environment (ex. Growing up in city vs. suburb) 

• Perinatal (period surrounding childbirth) complications 

• 1st or 2nd trimester maternal infection or malnutrition 

• Use of cannabis/stimulants 

• Father > 35 years old at point of conception

What are some structural schizophrenia brain changes?

• Widespread decrease grey matter 

  • Frontal and temporal cortices

• Pronounced thinning of dorsolateral prefrontal cortex (dlPFC) 

  • Critical for working memory 

• Volume loss results in enlarged ventricles

  • Due to reduction in cell processes (axons + dendrites) 

• Prefrontal cortex: 

  • Loss of dendritic spine density 

  • Fewer GABAergic interneurons 

• Hippocampus: 

  • Atypical layering structure

  • Atypical neuron shape

Functional Brain Changes

Abnormal (hypoactive) frontal + temporal lobes (including hippocampus) 

Non-Pharmacological Treatments 

Cognitive Behavioural Therapy (CBT) for management of positive + negative symptoms when combined with medication 

Pharmacological Treatment

Most common treatments for positive symptoms: antipsychotic drugs 

• Typical/older

  • Act on dopamine 

  • Can have movement disorder side effects 

• Atypical/newer

  • Act on dopamine, serotonin, and other receptors 

  • Can have metabolic side effects (ex. Weight gain, diabetes) 

Limited options for treating negative symptoms of schizophrenia

What are the two theories on schizophrenia?

1. Dopamine Theory 

2. Glutamate Hypofunction theory

Dopamine Theory

Theory that schizophrenia is caused by too much activity @ dopamine receptors. Based on sevreal findings:

1. The brains of individuals with Parkinson’s disease have marked dopamine depletions; antipsychotic drugs produce symptoms that are similar to Parkinson’s disease.

2. Drugs known to increase dopamine levels (e.g., amphetamine, cocaine) produce symptoms of schizophrenia.

3. The efficacy of an antipsychotic drug is correlated with the degree to which it blocks activity at dopamine D2 receptors

What are the problems with dopamine theory?

1. Newer atypical antipsychotic drugs produce a wide variety of changes in the brain + just as good as traditional antipsychotics 

2. Takes 2-3 weeks for antipsychotic drugs to work, yet their effects on dopamine receptor activity are immediate

3. Most patients show no significant improvement to the first antipsychotic they are given.

Glutamate Hypofunction theory

• Brain is organized with lots of glutamate-producing excitatory neurons (medial PFC, frontal + temporal lobes) 

• GABA neurons are downstream of glutamate neuron 

• More glutamate = more inhibition of GABA neuron 

• Rest of brain is downstream of GABA neuron 

• Insufficient glutamate = insufficient inhibition = overactivity in what should have been inhibited 

• Unbalanced excitation

As glutamate activity goes up, inhibition of gaba neuron goes down. If glutamate signalling becomes abnormal, can lead to: 

1. Less GABAergic transmission (ex. Decreased inhibition of downstream cells) 

2. Widespread pattern of too much activity (unbalanced excitation vs. inhibition) 

What do we know about dysfunction triggers?

• Not a lot…

• Could be considered neurodevelopmental disorder with both genetic + environmental components 

• We know there is big reduction in NMDA synapses in teens + twenties. Possibilities: 

  • Dysregulated plasticity (weak synapses persisted too long/were not pruned) 

  • Excessive immune activation (microglia) and overly-aggressive synaptic pruning