Ch. 18 - mental illness - Textbook Notes for Exam 3 PDF

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Chapter 18 Biopsychology of Psychiatric Disorders SCHIZOPHRENIA LO 18 what is Schizophrenia? Overlaps with several other different disorders, hence a Positive symptoms seem to represent an excess of typical function Negative symptoms seem to represent reduction or loss of typical function Diagnosis ...

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Chapter 18 – Biopsychology of Psychiatric Disorders SCHIZOPHRENIA LO 18.1 what is Schizophrenia?  Overlaps with several other different disorders, hence it’s a “schizophrenia spectrum”  Positive symptoms = seem to represent an excess of typical function Negative symptoms = seem to represent reduction or loss of typical function Diagnosis = 1 month of frequent recurrence of any 2 of these symptoms; provided that one of the symptoms is delusions, hallucinations, or disorganized speech. Positive Symptoms Delusions = of being controlled, of persecution, of grandeur Hallucinations = imaginary voices making critical comments or telling patients what to do Inappropriate affect = failure to react with the appropriate emotion to positive or negative events Disorganized speech or thought = illogical thinking, peculiar association among ideas, belief in supernatural forces Odd behavior = difficulty performing everyday tasks, lack of personal hygiene, talking in rhymes Negative Symptoms Affective flattening = diminished emotional expression Avolition = reduction or absence of motivation Catatonia = remaining motionless, often in awkward positions for long periods.

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LO 18.2 Causal Factors in Schizophrenia  Schizophrenia has a GENETIC BASIS, but no single  Differences in experience has a significant effect on the development of schizophrenia  Some people inherit a potential for schizophrenia – may or may not be activated by experience.  Multiple causes, can include = birth complications maternal stress, prenatal infections, socioeconomic factors, urban birth or residing in an urban setting, and childhood adversity.  Early experiences are thought to alter the typical course of neurodevelopment. LO 18.3 Discovery of the Frist Antipsychotic Drugs  First major breakthrough: accidental discovery of the first antipsychotic drug = a drug that is meant to treat certain symptoms of schizophrenia and bipolar disorders  Chlorpromazine = alleviates the symptoms of schizophrenia – agitated patients were calmed and emotionally blunted patients were activated by it. o But this is NOT A CURE  Psychosis – loss touch of reality (characteristic of schizophrenics).  Reserpine – active ingredient of snakeroot plant; similar benefits with chlorpromazine to alleviate symptoms of schizophrenia. (No longer in use because it produces a dangerous decline in blood pressure).  Antipsychotic effects of chlorpromazine and reserpine similar in 2 ways: o Manifested only after a patient has been medicated for 2-3 weeks o Onset is associated with motor effects similar to symptoms of Parkinson’s disease  Similarities suggest that chlorpromazine and reserpine were acting through the SAME MECHANISM – one that was related to Parkinson’s disease. LO 18.4 Dopamine Theory of Schizophrenia  Dopamine theory of schizophrenia = the theory that schizophrenia is caused by too much dopamine and, conversely, that antipsychotic drugs exert their effects by decreasing dopamine levels.

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Supported by 2 established facts: o Antipsychotic drug reserpine was known to deplete the brain of dopamine and other monoamines by breaking down the synaptic vesicles in which neurotransmitters are stored o Drugs such as amphetamine and cocaine, which can trigger episodes that resemble schizophrenia is healthy users, were known to increase the extracellular levels of dopamine and other monoamines in the brain. Carlsson and Lindqvist (1963) research – discovered that chlorpromazine and reserpine antagonize transmission at dopamine synapses but in different ways: o Reserpine by depleting the brain of dopamine o Chlorpromazine by binding to dopamine receptors - It binds to dopamine receptors without activating them, and in so doing, keeps dopamine from activating them. Main factor in schizophrenia – high levels of activity at dopamine receptors Snyder and colleges findings o Chlorpromazine and other effective antipsychotic drugs had a high affinity for dopamine receptors; while ineffective antipsychotics had a low affinity. o HOWEVER, there were several exceptions – e.g. haloperidol, one of the most potent antipsychotic drug, had relatively low affinity for dopamine receptors. Dopamine binds to more than one dopamine receptor subtypes (5 total) o Phenothiazines bind effectively to both D1 and D2 receptors  Such as chlorpromazine o Butyrophenones all bind effectively to D2 receptors, but not D1  such as haloperidol Findings: Schizophrenia is caused by hyperactivity specifically at D2 receptors, rather than at dopamine receptors in general. o Typical antipsychotics bind to D2 receptors is highly correlated with their effectiveness in suppressing the symptoms of schizophrenia. Limits to D2 Receptors o Therapeutic effects are not apparent for several weeks o Most antipsychotics are only effective in the treatment of schizophrenia’s positive symptoms, but not its negative symptoms.

LO 18.5 Schizophrenia: Current Research and Treatment ATYPICAL ANTIPSYCHOTICS  Atypical antipsychotics – second-generation antipsychotics; often the choice for treatment o Drugs that are effective against schizophrenia but yet do not bind strongly to D2 receptors o Clozapine – first atypical antipsychotic to be approved; affinity for D1, D4, and several serotonin and histamine receptors.  Initially claimed that atypical antipsychotics were more effective, but not much evidence.  Be aware that: 1. Some D2 receptors antagonists have no antipsychotic actions 2. Drugs that enhance the effects of glycine or block the effects of glutamate are proving to be effective treatments for schizophrenia in preliminary tests 3. There is a growing appreciation of the role of glutamatergic dysregulation in the development of schizophrenia.

Chapter 18 – Biopsychology of Psychiatric Disorders RENEWED INTEREST IN HALLUCINOGENIC DRUGS  Psychedelic drugs – drugs whose primary action is to alter perception, emotion, and cognition; began with the discovery of LSD o Classical hallucinogen = LSD, psilocybin, and mescaline o Dissociation hallucinogen = ketamine and phencyclidine o Cannabinoids  Research on utilizing psychedelic drugs to study the mechanisms of schizophrenia and other psychiatric disorders  brain imaging techniques  2 conclusions o The effects of classical hallucinogens mimic positive symptoms of schizophrenia o The effect of dissociative hallucinogens mimic the negative symptoms of schizophrenia by acting as antagonists of glutamate receptors. MECHANSIMS OF SCHIZOPHRENIA-RELATED GENES  Schizophrenia-related genes have been shown to o Disrupt neural proliferation and migration o Synaptic pruning during neurodevelopment o Myelination o Transmission at glutamatergic and GABAergic synapses  Some genes that increase a person’s susceptibility to schizophrenia have also been linked to other psychiatric and neurological disorders. SCHIZOPHRENIA AND BRAIN STRUCTURE CHANGES  First generation of studies reported enlarged ventricles and fissures  reduced brain volume  Subsequent studies show – hippocampus, amygdala, thalamus, and nucleus accumbens found to be significantly SMALLER in those with schizophrenia.  Generally, schizophrenia-related volume reduction develop in both gray and white matter, and they are most consistently observed in the temporal lobes.  4 main findings 1. Individuals who have not been diagnosed with schizophrenia but are at risk for the disorder display volume reductions in some parts of the brain. 2. Extensive brain changes already exist when patients first seek medical treatment and receive their first brain scans. 3. Subsequent brain scans reveal that the brain changes continue to develop after the initial diagnosis 4. Alteration to different areas of the brain develop at different rates. DEPRESSIVE DISORDERS LO. 18.6 Defining Depressive Disorders  Anhedonia – loss of capacity to experience pleasure  Clinical depression/major depressive disorder = patients are unable to meet the essential requirements of their daily lives (keep a job, personal hygiene, eat, maintain social contacts), sleep disturbances, suicidal thoughts – 2 weeks or longer  Reactive depression – triggered by a negative experience  Endogenous depression – depression with no apparent cause  In adults, clinical depression is often comorbid – tendency for 2 health conditions to occur together in the same individual; ex: with anxiety disorder, coronary heart disease, diabetes.

Chapter 18 – Biopsychology of Psychiatric Disorders LO 18.7 Causal Factors in Major Depressive Disorder  Genetic roles; role of stress and trauma in the etiology of depression.  2 major subtypes of depression o Seasonal affective disorder (SAD) = episodes of depression and lethargy typically recur during particular season (usually during winter months)  Triggered by the reduction of sunlight o Peripartum depression = intense, sustained depression experienced by some women during pregnancy, after they give birth, or both. LO 18.8 Antidepressant Drugs 5 major classes of drugs have been used for the treatment of depressive disorders: monoamine oxidase inhibitors, tricyclic antidepressants, selective monoamine-reuptake inhibitors, atypical antidepressants, and NMDA-receptor antagonists. MONOAMINE OXIDASE INHIBITORS  Iproniazid – the first antidepressant drug; monoamine agonist  o Increases levels of monoamines by inhibiting the activity of monoamine oxidase (MAO) o MAO = the enzyme that breaks down monoamine neurotransmitters in the cytoplasm  Side effects of MAO inhibitors  cheese effect (the most dangerous) o If you consume tyramine-rich foods (cheese, wine, pickles)  run high risk of stroke. TRICYCLIC ANTIDEPRESSANTS  Chemical structures include 3 rings of atoms  Imipramine – the first tricyclic antidepressant  Blocks the reuptake of both serotonin and norepinephrine, thus increasing their levels in the brain.  SAFER than MAO inhibitors SELECTIVE MONOAMINE-REUPTAKE INHIBITORS  Selective serotonin-reuptake inhibitors (SSRIs) = are serotonin agonists that exert their agonistic effects by blocking the reuptake of serotonin from synapses.  Fluoxetine (marketed as Prozac) was the first SSRI to be developed. o Slight variation of that of imipramine and other tricyclic antidepressants; and also no more effective than imipramine in treating depression.  Fluoxetine and other SSRIs are more popular for 2 reasons: 1. Have fewer side-effects than tricyclics and MAO inhibitors 2. Act against a wide range of psychological disorders in addition to depression.  Selective norepinephrine reuptake inhibitors (SNRIs) o These proven to be just effective as the SSRIs in treating depression (e.g. reboxetine) o Also effective, drugs that block the reuptake of more than one monoamine neurotransmitter (e.g. venlafaxine).

Chapter 18 – Biopsychology of Psychiatric Disorders ATYPICAL ANTIDEPRESSANTS  Catch-all class compromising drugs that have many different modes of action.  bupropion – several effects on neurotransmission: o blocker of dopamine and norepinephrine reuptake o blocker of nicotinic acetylcholine receptors  agomelatine – melatonin receptor agonist NMDA-RECEPTOR ANTAGONISTS  1990s – positive effect of antagonizing the glutamate NMDA receptor on depressive disorder  Dissociative hallucinogen ketamine – single low dose can rapidly reduce depression, but has undesirable side effects  researchers trying to find more selective NMDA-receptor antagonists with fewer side effects. EFFECTIVENESS OF DRUGS IN THE TREATMENT OF DEPRESSIVE DISORDERS  Only 25% of depressive individuals were actually helped by the antidepressants  Meta-analyses  found that antidepressants were not significantly better than placebo in treating patients with mild or moderate depression. o Only the severely depressed seemed to benefit. LO 18.9 Brain Differences in Depression  Consistent reduction in gray matter volumes in the prefrontal cortex, hippocampus, amygdala, and cingulate cortex have been observed.  White matter reduction, but reliably in the frontal cortex.  Atypical activity in frontal, cingulate, and insular cortices LO 18.10 Theories of Depression MONOAMINE THEORY OF DEPRESSION  Depression is associated with underactivity at serotonergic and noradrenergic synapses o Most antidepressant drugs are agonists of serotonin, norepinephrine, or both o Autopsy studies show high levels of norepinephrine and serotonin receptors in deceased depressed individuals   Implies a deficit in monoamine release  Up-regulation = an increase in the number of receptors for a neurotransmitter in response to decreased release of that neurotransmitter.  2 lines of evidence that challenge this theory 1. Monoamine agonists are not effective in treatment; only slightly better than a placebo 2. Other neurotransmitter lay a role in the development of depression. NEUROPLASTICITY THEORY OF DEPRESSION  In a nutshell, the neuroplasticity theory of depression is that depression results from a decrease of neuroplastic processes in various brain structures.  General support from 2 kinds of research: 1. Research showing that stress and depression are associated with the disruption of various neuroplastic processes. 2. Research showing that antidepressant treatments are associated with an enhancement of neuroplastic processes.  Brain-derived neurotropic factor (BDNF) might be biomarker o Biomarker = a biological state that is predictive of a particular disorder.

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Increased blood levels of BDNF might be a biomarker for the successful treatment of depression. Hypothesized: antidepressants  INCREASE BDNF levels INCREASE certain neuroplastic process (e.g. adult hippocampal neurogenesis)  alleviation of depression.

LO 18.11 Treatment of Depression with Brain Stimulation REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION  Repetitive transcranial magnetic stimulation (rTMS) = form of transcranial magnetic stimulation that involves the noninvasive delivery of repetitive magnetic pulses at either high frequencies or low frequencies.  to specific cortical areas – usually prefrontal cortex DEEP BRAIN STIMULATION  Chronic brain stimulation through an implanted electrode – in an area of the white matter of the anterior cingulate gyrus in the medial prefrontal cortex.  20 patients selected (b/c they repeatedly failed to respond to conventional treatments) – 60% showed substantial improvements. BIOPOLAR DISORDERS LO 18.12 Defining Bipolar Disorder  Hypomania = characterized by a reduced need for sleep, high energy, and positive affect. o People are talkative, energetic, impulsive, positive, and very confident. o Can be effective at certain jobs and ca be great fun to be with.  Mania = similar to hypomania but taken to the EXTREME; additional symptoms – delusions of grandeur, overconfidence, impulsivity, and distractibility. o Involves psychosis – loss touch of reality o Leaves behind a trail of unfinished projects, unpaid bills, and broken relationship.  Bipolar disorder type II = person only experience bouts of depression and hypomania  Bipolar disorder type I = experience bouts of depression, hypomania, and mania.  Bipolar disorders DO NOT involve rapid alternations in mood; rather, the mood episodes often last weeks to months. o Rapid cycling bipolar disorder – involves 4 or more mood episodes per year  S.B. Case: psychiatric patients often careen from one diagnosis to another. LO 18.13 Causal Factors in Bipolar Disorders  Highly heritable; several genes are linked  Example – genes that code for particular calcium channels and for particular proteins found at the nodes of Ranvier. LO 18.14 Mood Stabilizers  Mood stabilizers = drugs that effectively treat depression or mania without increasing the risk of mania or depression, respectively.  Lithium (a simple metallic ion) – first drug to act as a mood stabilizer; highly effective o But does not eliminate ALL symptoms o Adverse side effects: weight gain, tremor, blurred vision, dizziness  John Cade experiment with Guinea pigs = found that lithium had a dramatic effect on manic patients o Hypothesized that manic patients have lower levels of lithium than non-manic patients

Chapter 18 – Biopsychology of Psychiatric Disorders LO 18.15 Brain Differences Associated with Bipolar Disorders  Reduction in gray matter volume have been reported  Several specific brain structures smaller in patients with bipolar disorders – medial prefrontal cortex, the left anterior cingulate, the left superior temporal gyrus, certain prefrontal regions, and hippocampus.  Meta-analyses  atypical activation and atypical functional connectivity LO 18.16 Theories of Bipolar Disorders  Lack of clear understanding of mechanisms underlying various mood stabilizers and by the lack of an adequate animal model of bipolar disorder.  But, several physiological disturbances that have been identified = o Hypothalamic-pituitary-adrenal (HPA) axis dysregulation in bipolar disorders o Marked disruption in the circadian rhythms in both patients with bipolar disorders and their nonbipolar relatives. o Alterations in GABA, glutamate, and monoamine neurotransmission in patients with bipolar disorders o BDNF levels are lower in patients with bipolar disorder (whether they are depressed or manic). ANXIETY DISORDERS  Anxiety – chronic fear that persists in the absence of any direct threat – common psychological correlate of stress; adaptive if it motivates coping behavior.  Anxiety disorder – becomes so severe that it disrupts functioning. o Associated with feelings of anxiety and with a variety of physiological stress reactions >>  Tachycardia – rapid heartbeat  Hypertension – high blood pressure  Nausea, breathing difficulties, sleep disturbances, and high glucocorticoid levels. o 14-34% of people suffer anxiety disorder at some point; twice in females than males LO 18.17 Four Anxiety Disorders 1. Generalized anxiety disorder = characterized by stress responses and extreme feelings of anxiety and worry about a large number of different activities or events. 2. Specific Phobias = involve a strong fear or anxiety about particular objects (e.g. birds, spiders), or situations (e.g. enclosed spaces, darkness). o Person will usually try to avoid those specific objects or situations that are anxiety producing. 3. Agoraphobia = pathological fear of public places and open spaces. o Although it might be considered as a specific phobia, it is generally considered to be more incapacitating than most specific phobias and is thus treated as a separate diagnostic category in the DMS-5. 4. Panic disorder = characterized by recurrent rapid-onset attacks of extreme fear and severe symptoms of stress (e.g. choking, heart palpitations, shortness of breath). o Panic attacks also occur in certain cases of generalized anxiety disorder, specific phobia, and agoraphobia.

LO 18.18 Etiology of Anxiety Disorders

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Role of experience in shaping the disorder is often apparent Has a significant genetic component – heritability estimates 30-50% o Higher for MZ twins than DZ twins o But no specific genes have yet been linked to anxiety disorders

LO 18.19 Pharmacological Treatment of Anxiety Disorders BENZODIAZEPINES  Ex: diazepoxide (marketed as Librium) and diazepam (marketed as Valium)  Benzodiazepines are the most widely prescribed psychoactive drugs; approx.. 10% of adult North Americans are currently taking them.  Adverse side effects – sedation, ataxia (disruption of motor activity), tremor, nausea, and a withdrawal reaction that includes rebound anxiety.  Highly addictive; should be prescribed only for short-term. SEROTONIN AGONISTS  Buspirone – selective agonist effects at one subtype of serotonin receptor, the 5-HT1A receptor. o Mechanism is not entirely understood, does not function as an SSRI  Main advantage over benzodiazepines  produces anxiolytic (antianxiety) effects without producing ataxia, muscle relaxation, and sedation o But does have other side effects – dizziness, nausea, headache, insomnia ANTIDEPRESSANT DRUGS ...