Chapter 18 Biopsychology of Psychiatric Disorders

1. Chapter 18Biopsychology 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