Chapter 15 Behavioral Neuroscience of Psychiatric Disorders The

Chapter 15 Behavioral Neuroscience of Psychiatric Disorders The Brain Unhinged This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program

Copyright 2007 by Allyn and Bacon Psychiatric Disorders AKA psychological disorders Disorders of psychological function that warrant 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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? Copyright 2007 by Allyn and Bacon

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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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? Copyright 2007 by Allyn and Bacon Dopamine (DA) Theory of Schizophrenia

1960 link between DA and Parkinsons 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

Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon Copyright 2007 by Allyn and Bacon 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 dont 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 Copyright 2007 by Allyn and Bacon Problems with the D2 Theory

Positive symptoms - presence of abnormal incoherence, Negative absence of normal flat hallucinations, delusions 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon Antidepressant Drugs

Monoamine oxidase inhibitors (MAOIs) Tricyclic antidepressants Prevent breakdown of monoamines Must avoid foods high in tyramine cheese effect Block reuptake of serotonin and norepinephrine Safer than MAOIs

Selective monoamine reuptake inhibitors Lithium mood stabilizer Not a drug treats bipolar Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon Monoamine Theory of Depression Underactivity of the monoamines serotonin and norepinephrine 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 Copyright 2007 by Allyn and Bacon How Prozac Works Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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? Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon 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

Copyright 2007 by Allyn and Bacon Copyright 2007 by Allyn and Bacon 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 Copyright 2007 by Allyn and Bacon Tourettes 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 Copyright 2007 by Allyn and Bacon Tourettes Syndrome

Usually treated with neuroleptics although effectiveness is not wellestablished Effectiveness of D blockers suggests 2 abnormality in basal ganglia-thalamuscortex feedback circuit Copyright 2007 by Allyn and Bacon