Dysfunction associated with psychiatric disorders (+ Schizophrenia)

Question 1

Why classify psychiatric dysfunction (mental illness) into types? BROAD ANSWER

Answer 1

Broadly: to seek similarities and differences among patient groups

Question 2

Why classify psychiatric dysfunction (mental illness) into types? 4 SPECIFIC

Answer 2

1. To guide treatment choices
2. To allow clinicians to communicate
3. To serve parties who require a diagnosis (e.g., insurance, CFA, legal system)
4. To permit research (via categorization): into causes, treatment responsiveness, prognosis

Question 3

Classification of psychiatric disorders

Answer 3

• Primarily via the Diagnostic and Statistical Manual of Mental Disorders (APA)
• Atheoretical (not dependent on theory)
• Operationalist (meaning of a scientific concept depends upon the procedures used to establish it)
• Categorical

Question 4

DSM-I (1952) and DSM-II (1968):

Diagnosis of mental illnesses over time (process of DSM development)

Answer 4

• Heavy on psychodynamics (mental illness as “personality reactions” to stress)
• Intended to support data collection, particularly among WWII vets

Question 5

1960s - psychiatry’s “crisis of legitimacy”

Diagnosis of mental illnesses over time (process of DSM development)

Answer 5

• Argued that psychiatry was harmful & a means to control non-conformists
• Held that mental illness was a myth
• RESULT - major changes made to establish the DSM-III (1980) and DSM-IV (1994): exhaustive overhaul, attempted to standardize diagnosis

Question 6

DSM-5 (2013)

Diagnosis of mental illnesses over time (process of DSM development)

Answer 6

long process of working groups and reviewing current evidence, better attempts to control conflicts of interest

Question 7

DSM-5 definition of mental disorders (3)

Answer 7

1. Characterized by clinically significant disturbance in an individual’s cognition, emotion regulation, or behavior that…
2. reflects a dysfunction in the psychological, biological, or development processes underlying mental functioning, and
3. is associated with significant distress or disability in social, occupational, or other important activities.

Question 8

DSM-5 explicit exclusions

Answer 8

• 1. An expectable or culturally approved response to a common stressor or loss, such as the death of a loved one, is not a mental disorder.
• 2. Socially deviant behavior (e.g. political, religious, or sexual) and conflicts that are primarily between the individual and society are not mental disorders unless the deviance or conflict results from a dysfunction in the individual, as described above.

Question 9

Criticisms of the DSM (5)

Answer 9

1. Level of detail
2. Overlap
3. Authority
4. Comparator
5. Heterogeneity of criteria

Question 10

Level of detail

Criticism

Answer 10

“there are almost 24,000 possible symptom combinations for panic disorder in DSM-5, compared with just one possible combination for social phobia”

Question 11

Overlap

Criticism

Answer 11

• For many diagnoses, 2 people could be diagnosed with no overlapping symptoms
• High overlap between some diagnoses e.g., PTSD & MDD

Question 12

Authority: Who judges distress/impairment?

Criticism

Answer 12

Clinician vs self vs unclear

Question 13

Comparator

Criticism

Answer 13

• “decreased need for sleep…” and “more talkative than usual…” (to self)
• “excessive or inappropriate guilt…” (normative)
• “feelings of worthlessness” (none)

Question 14

Big picture trend:

Answer 14

Normative assumptions

• Normative: Evaluation of right or wrong, Ought, should
• Descriptive: What is or would be

Question 15

What were some controversial illnessess/components of the DSM?

Answer 15

• Masturbation (19th c.)
• Drapetomania – an “illness” causing black slaves to attempt escape
• Homosexuality: a disorder in DSM-I and DSM-II, removed for DSM-III following protests by gay activists and internal pressure from the “Gay PA”

Question 16

Deinstitutionalization

Answer 16

• Movement, starting in the 1950s and 1960s, to replace long-stay psychiatric facilities with community mental health services
• Possible with antipsychotic drugs such as chlorpromazine
• Without adequate support, people with mental illness are at higher risk of incarceration, being unhoused - “balloon theory”

Question 17

Mental illness and violence

Answer 17

• In the absence of substance use disorder, people with mental illness are not more violent than others from their same neighbourhoods (i.e., controlling for poverty, etc.)

Question 18

Schizophrenia

Question 19

Schizophrenia: DSM-5 criteria - A

Answer 19

2+ of the following:

1. Delusions
2. Hallucinations
3. Disorganized speech (e.g., frequent derailment or incoherence)
4. Grossly disorganized or catatonic behaviour
5. Negative symptoms (i.e., diminished emotional expression or avolition)

Question 20

Schizophrenia: DSM-5 criteria - B

Answer 20

Level of functioning in one or more major life areas is below the level achieved prior to the onset

Question 21

Schizophrenia: DSM-5 criteria - C

Answer 21

Continuous signs of the disturbance persist for at least 6 months

Question 22

Schizophrenia: DSM-5 criteria - D

Answer 22

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

Question 23

Schizophrenia: DSM-5 criteria - E

Answer 23

Not attributable to the physiological effects of a substanceor another medical condition.

Question 24

How is Schizophrenia = “splitting of the minds”?

Answer 24

• Not between two personalities (i.e., dissociative identity disorder)
• Instead, between personality, memory, emotion, perception, etc.

Question 25

Symptoms of schizophrenia: 3 categories

Answer 25

1. Positive symptoms 2. Negative symptoms 3. Cognitive abnormalities

Question 26

Positive symptoms ## Footnote Symptoms of schizophrenia: 3 categories

Answer 26

mental phenomena that do not occur in healthy people

Question 27

What can positive symptoms include?

Answer 27

* **Hallucinations**: **perceptions without sensory cause** * **Often auditory** – voices, noises, music * Command hallucinations have a high risk of harm including suicide * **Delusions**: **beliefs that are not realistic or culturally appropriate** * Can be quite varied

Question 28

Negative Symptoms ## Footnote Symptoms of schizophrenia: 3 categories

Answer 28

Negative symptoms **resulting from an impairment of normal function**

Question 29

What can Negative Symptoms include?

Answer 29

* Blunted emotional responses (“affective flattening”) * Impoverished content of thought and speech (disturbed attention) * Reduced social motivation

Question 30

Schizophrenic speech

Answer 30

Grammar is **reasonably intact but content wanders or is incoherent** – “loosening of associations"

Question 31

Common development of schizophrenia:

Answer 31

* ~0.5-1.5% of population * Slightly more common in men * Onset usually teens to early 30s * Often preceded by a prodromal period

Question 32

Risk factors of Schizophrenia

Answer 32

* Genetics * Growing up in an urban environment * 1st or 2nd trimester maternal infection or malnutrition * Perinatal complications * Cannabis or stimulant use * Paternal age >35 years (at the point of conception)

Question 33

Brain changes - Structural

Answer 33

* Widespread **decreased grey matter**, particularly in frontal and temporal cortices * Pronounced **thinning of dorsolateral prefrontal cortex** (dlPFC) (critical for working memory)

Question 34

Brain changes - Structural volume loss results in...

Answer 34

* ...enlarged ventricles (fluid filled spaces in the brain) * Overall, volume loss is **not due to cell death** but rather **a reduction in cell processes (same number of cells but less axons and dendrites)**

Question 35

Brain changes - Structural: Prefrontal Cortex

Answer 35

* Loss of dendritic spine density * There is ONE cell that there is fewer of: **GABAergic interneuron**

Question 36

Brain changes - Structural: Hippocampus

Answer 36

In the Hippocampus (in the medial temporal lobe), there is both: * Atypical **layering structure** * Atypical **neuron shape**

Question 37

Brain changes - Functional

Answer 37

**Abnormal (often *hypo*active) frontal and temporal lobes** **including hippocampus** (same areas that are structurally affected)

Question 38

Non-pharmacological treatments

Answer 38

**Cognitive Behavioural Therapy (CBT)** has shown some promise for the management of positive and negative symptoms when combined with medication

Question 39

Pharmacological treatment

Answer 39

The most common treatments (for positive symptoms) are **antipsychotic drugs**

Question 40

Pharmacological treatment: **TYPICAL antipsychotic drugs**

Answer 40

**Typical** (older) * E.g., chlorpromazine (Thorazine), haloperidol (Haldol) * **Act on dopamine** * **Can have movement disorder side effects**

Question 41

Pharmacological treatment: **ATYPICAL antipsychotic drugs**

Answer 41

**Atypical** (newer) * E.g., olanzapine (Zyprexa), aripiprazole (Abilify) * **Act on dopamine, serotonin, and other receptors** * **Can have metabolic side effects (weight gain, diabetes...)**

Question 42

Two theories of schizophrenia

Answer 42

1. Dopamine theory 2. Glutamate hypofunction theory

Question 43

Dopamine theory ## Footnote Two theories of schizophrenia

Answer 43

maybe schizophrenia is caused by too much activity at dopamine receptors

Question 44

Dopamine theory - based on several findings:

Answer 44

1. **The brains of individuals with Parkinson’s disease have marked dopamine depletions**; and **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** (maybe it's *too much* dopamine) 3. **The efficacy of an antipsychotic drug is correlated with the degree to which it blocks activity/tightly binds at dopamine D2 receptors.**

Question 45

In the 80s and 90s, researchers began to realize that the theory had several major problems:

Answer 45

1. The **newer “atypical” antipsychotic drugs produce a wide variety of changes in the brain (NOT JUST FOCUSED ON DOPAMINE) and were just as good as traditional antipsychotics** (challenges a dopamine-only effect = something else is going on) 2. It takes 2-3 weeks for antipsychotic drugs to work on delusions/hallucinations, yet their effects on dopamine receptor activity are **immediate** (why is there a lag in improving symptoms?) 3. Most patients show no significant improvement to the first antipsychotic they are given.

Question 46

Glutamate hypofunction theory

Answer 46

Finding: **phencyclidine** (PCP) and **ketamine** can **induce negative symptoms and psychosis and *act antagonistically upon NMDA receptors*** – a specific type of receptor for the neurotransmitter glutamate * Basically: **we can produce something that looks like schizophrenia with these drugs, which we know act on glutamate** * NMDA receptors allow calcium to enter the cell, which can cause many biological changes * Glutamate = excitatory * GABA = inhibitory

Question 47

Glutamate hypofunction theory - how does it work?

Answer 47

1. Glutamate neuron (excitatory) may be in the medial PFC, frontal and temporal lobes 2. Glutamate neuron synapses on to the GABA neuron (inhibitory) - meaning the more it fires, the more it inhibits whatever its firing to * HOW? through NMDA receptors for glutamate * RESULT: send inhibitory GABA signals onto other neurons; the more excitatory a glutamate neuron is, the more GABA neurons inhibit the rest of the brain

Question 48

Glutamate hypofunction theory - If glutamate signalling becomes abnormal, this can lead to..

Answer 48

1. **Less GABAergic transmission** (i.e., decreased inhibition of downstream cells = ***less*** **inhibition of the brain) leading to...** 2. **A widespread pattern of too much activity** (unbalanced excitation vs inhibition)

Question 49

Glutamate hypofunction theory - what triggers the dysfunction?

Answer 49

* We don’t fully know! * Could be considered a neurodevelopmental disorder with both genetic and environmental components We *do* know that there is a big reduction in NMDA synapses in teens & twenties. This might reflect: * Dysregulated plasticity (maybe weak synapses persist too long in childhood?) * Excessive immune activation (microglia) and overly-aggressive synaptic pruning