1. Chapter 18 Biopsychology of Psychiatric Disorders
The Brain Unhinged

2. Psychiatric Disorders
AKA psychological disorders
Disorders of psychological function that require treatment by a mental health professional
Neuropsychological disorders - a product of dysfunctional brains – but so are psychiatric disorders
Historically:
Neuropsychological disorders – brain problem
Psychiatric – mind problem

3. Psychiatric Disorders
More influenced by experiential factors
Tend to be the product of more subtle forms of brain pathology
Underlying dysfunction may yet to be identified, but are suggested by the effectiveness of treatments
Tend to be less well understood

4. Psychiatric Disorders
What are the advantages and disadvantages of societal acceptance of psychological disorders as diseases with a biological basis?
Are there some conditions for which this acceptance already exists?

5. Anxiety Disorders Anxiety – fear in the absence of threat
Anxiety disorder – when anxiety interferes with normal functioning
Accompanied by physiological symptoms – tachycardia, hypertension, sleep disturbances, nausea, etc.
Most prevalent psychiatric disorders

6. Anxiety Disorders
Generalized – stress and anxiety in the absence of a causal stimulus
Phobic – similar to generalized, but triggered by a stimulus
Panic disorders – may occur with other disorders, but also alone
Obsessive-compulsive disorders (OCDs) – obsessive thoughts alleviated by compulsive actions
Posttraumatic stress disorder

7. Treatment of Anxiety Disorders
Benzodiazepines (Librium, Valium)
Also used as hypnotics, anticonvulsants, muscle relaxants
GABAA agonists – bind to receptor and facilitate effects of GABA
Highly addictive
Serotonin agonists (Buspirone, SSRIs)
Reduce anxiety without sedation and other side effects

8. The GABA Receptor

9. Animal Models of Anxiety
Assess anxiolytic potential of drugs - assume that defensive behaviors are motivated by fear, and that fear and anxiety are comparable
Elevated-plus-maze: time in open arms indicates less anxiety
Defensive-burying: More time burying, more anxiety
Risk-assessment test: Time freezing and assessing risk indicate anxiety level
Validated by effectiveness of benzodiazepines – but not all anxiety treated with such drugs

10. Neural Bases of Anxiety Disorders
Drugs suggest a role for serotonin and GABA
Amygdala, due to its role in fear and defensive behavior, thought to be involved
No pathology yet identified

11. Affective Disorders
Depression – normal reaction to loss, abnormal when it persists or has no cause
Mania – opposite of depression
Bipolar affective disorder
Depression with periods of mania
Unipolar – depression only
Reactive – triggered by negative event
Endogenous – no apparent cause

12. Causal Factors in Affective Disorders
Affective disorders are very common
~6% suffer from unipolar affective disorder at some point, ~1% from bipolar
Genetics
Concordance rate higher for bipolar than unipolar
Stressful experiences
More stress reported by those seeking treatment for depression than controls

13. Antidepressant Drugs Monoamine oxidase inhibitors (MAOIs)
Prevent breakdown of monoamines
Must avoid foods high in tyramine – ‘cheese effect’
Tricyclic antidepressants
Block reuptake of serotonin and norepinephrine
Safer than MAOIs
Selective monoamine reuptake inhibitors
Lithium – mood stabilizer
Not a drug – treats bipolar

14. Selective monoamine reuptake inhibitors
Selective serotonin-reuptake inhibitors (SSRIs)
Prozac, Paxil, Zoloft
No more effective than tricyclics, but side effects are few and they are effective at treating other things
Selective norepinephrine-reuptake inhibitors (SNRIs)
Also effective

15. Effectiveness of Drug in Treating Affective Disorders
Results are comparable with MAOIs, tricyclics, and SSRIs
About 50% improve, compared to 25% of controls
Drugs help those experiencing depression, but do not prevent future episodes

16. Monoamine Theory of Depression
Underactivity of serotonin (5HT) and norepinephrine (NE)
Consistent with drug effects
Up-regulation of receptors at autopsy of depressed individuals consistent with this
Problem with theory – not all respond to monoamine agonists

17. Diathesis-Stress Model
Inherited genetic susceptibility (diathesis) + stress = depression
Support is indirect
Depressed people tend to release more stress hormones
Fail dexamethasone suppression test – normal negative feedback on stress hormones not functioning

18. Sleep Deprivation
More than 50% of depressed patients improve after one night of sleep deprivation.
Short-lasting: depression returns when normal sleep pattern resumes.
Not explained by any theory.
What does this suggest?

19. Brain Damage and Unipolar Depression
Amygdala
Prefrontal cortex
Both involved in perception and experience of emotion
Terminal structures of the mesotelencephalic DA system
Consistent with anhedonia (lack of pleasure) experienced by the depressed

20. Tourette’s Syndrome
A disorder of tics, involuntary movements or vocalizations
Begins in childhood
Major genetic component
Many also have signs of ADHD and/or OCD
No animal models, no genes identified, imaging difficult due to tics

21. Tourette’s Syndrome
Usually treated with neuroleptics – although effectiveness is not well-established
Effectiveness of D2 blockers suggests abnormality in basal ganglia-thalamus-cortex feedback circuit

22. Schizophrenia “splitting of psychic functions”
Refers to the breakdown of integration of emotion, thought, and action
Affects 1% of the population
A diverse disorder – multiple types exist with varied profiles
Some symptoms: delusions, hallucinations, odd behavior, incoherent thought, inappropriate affect
Only 1 needed for 8 months for diagnosis

23. Causal Factors in Schizophrenia
Clear genetic basis
Inherit an increased risk for the disorder
Multiple causes
Several different chromosomes implicated
Associated with various early insults – infections, autoimmune reactions, toxins, traumatic injury, stress
Appears that interference with the normal development of susceptible individuals may lead to development of the disorder

24. Antipsychotic Drugs
Much of our understanding of schizophrenia is a consequence of the drugs that are able to treat it
Chlorpromazine – calms many agitated schizophrenics and activates many emotionally blunt
Reserpine – also found to be effective
Both drugs are not effective for 2-3 weeks and Parkinson-like motor effects are seen
Suggesting a role for what neurotransmitter?

25. Dopamine (DA) Theory of Schizophrenia
1960 – link between DA and Parkinson’s Disease established
Side effects of antipsychotic drugs suggests role for dopamine: Drugs work by decreasing DA levels, disorder is a consequence of DA overactivity
Reserpine depletes brain of DA and other monoamines by making vesicles leaky
Amphetamine and cocaine are DA agonists and produce psychosis
Chlorpromazine antagonizes DA activity by binding and blocking DA receptors

26. Dopamine (DA) Theory of Schizophrenia
In general, the higher affinity a drug has for DA receptors, the more effective it is in treating schizophrenia
Haloperidol – an exception
While most antipsychotics bind to D1 and D2 receptors, it and the other butyrophenones bind to D2
Degree that neuroleptics bind to D2 receptors is correlated with their effectiveness

29. Problems with the D2 Theory
Clozapine, an atypical and effective neuroleptic, acts at D1, D4, and serotonin receptors. But – some binding to D2
Neuroleptics act quickly at the synapse, but don’t alleviate symptoms for weeks.
Indicates some slow-acting change must occur.
Schizophrenia associated with brain damage.
Little damage to DA circuitry
Damage not explained by DA theory
Neuroleptics are only effective for some

30. Problems with the D2 Theory
Positive symptoms - presence of abnormal
incoherence, hallucinations, delusions
Negative – absence of normal
flat affect, cognitive deficits, little speech
Conventional neuroleptics (D2 blockers) mainly effective at treating positive
Negative – might be caused by brain damage
May be best to think of schizophrenia as multiple disorders with multiple causes