Psychopathology: Biological Basis of Behavioral Disorders

Size: px

Start display at page:

Download "Psychopathology: Biological Basis of Behavioral Disorders"

Willa Shelton
5 years ago
Views:

1 1 6 Psychopathology: Biological Basis of Behavioral Disorders

2 16 Psychopathology: Biological Basis of Behavioral Disorders The Toll of Psychiatric Disorders Is Huge Schizophrenia is the major neurobiological challenge in psychiatry. Mood disorders are a major psychiatric category.

3 16 The Toll of Psychiatric Disorders Is Huge Epidemiology studies patterns of disease in a population. About one third of the U.S. population has reported symptoms of a psychiatric disorder. Delusions false beliefs held in spite of contrary evidence have been noted for centuries.

4 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Schizophrenia affects 1% to 2% of the population. Dissociative thinking, or impaired logical thought, is a key symptom. Other symptoms include auditory hallucinations, personalized delusions, and changes in affect (emotion).

5 Figure 16.1 Not So Beautiful Voices

6 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Positive symptoms are abnormal behaviors that are gained: Hallucinations Delusions Excited motor behavior

7 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Negative symptoms are the result of lost functions: Slow thought and speech Emotional and social withdrawal Blunted affect or emotional expression

8 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Schizophrenia is partly heritable. Family, twin, and adoptive studies show a higher incidence among biological relatives. Monozygotic (identical) twins share identical genes dizygotic (fraternal) have half of their genes in common.

9 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry If both twins suffer from schizophrenia, they are concordant for the disease. If only one member of a pair has it, they are discordant. For identical twins, the concordance rate is 50%, pointing to a genetic factor.

10 Figure 16.2 The Heritability of Schizophrenia

11 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry The rate of discordance suggests that other factors also contribute to the development of schizophrenia: Environmental influences Developmental difficulties, such as low birth weight and impaired motor coordination

12 Figure 16.3 Eye Tracking in Patients with Schizophrenia versus Normal People

Cerebral ventricles are enlarged, especially in males.

13 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Brains of some schizophrenic patients show structural changes. Cerebral ventricles are enlarged, especially in males. More-enlarged ventricles predict a poorer response to drug treatment. (antipsychotic drugs)

14 Figure 16.5 Identical Genes, Different Fates

15 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry The hippocampus and amygdala also differ in schizophrenics they are smaller. Pyramidal cells of the hippocampus have a disorganized arrangement, occurring during development. A theory is that prenatal exposure to influenza may be the cause.

16 Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 1)

17 Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 2)

18 Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 3)

19 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry The cortex also shows abnormalities of structure and function. Some studies show a loss of gray matter in the frontal lobes, and PET shows less metabolic activity.

20 Figure 16.8 Hypofrontality in Schizophrenia (Part 1) The hypofrontality hypothesis schizophrenia may be caused by underactivation of the frontal lobes.

21 Figure 16.8 Hypofrontality in Schizophrenia (Part 2)

22 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry The brain may also show neurochemical changes. Amphetamine psychosis caused by repeated use of amphetamines; resembles schizophrenia with paranoia, delusions, and auditory hallucinations.

23 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Chlorpromazine a member of the phenothiazine family can treat amphetamine psychosis and schizophrenia. These neuroleptic or antipsychotic drugs work by blocking dopamine D 2 receptors.

24 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Typical neuroleptic drugs are all antagonists at dopamine D2 receptors. The dopamine hypothesis schizophrenia results from excess synaptic dopamine or increased postsynaptic sensitivity to it.

26 Figure 16.9 Antipsychotic Drugs that Affect Dopamine Receptors (Part 1)

27 Figure 16.9 Antipsychotic Drugs that Affect Dopamine Receptors (Part 2)

28 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Antipsychotic drugs have long-term effects, such as dyskinesia distortion in voluntary movement Tardive dyskinesia shows repetitive movements involving the face, mouth, lips, and tongue. Supersensitivity psychosis can emerge when drug doses are lowered and receptors upregulate.

29 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry Problems with the dopamine hypothesis: Schizophrenics have normal DA metabolite levels Drugs block D 2 receptors much faster than symptoms are reduced Some patients show no change

30 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry A new class of drugs that successfully treat schizophrenia does not support the dopamine hypothesis. Atypical neuroleptics, like clozapine, block serotonin receptors as well as D 2 receptors. Some actually increase dopamine levels in the frontal cortex.

31 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry The glutamate hypothesis schizophrenia is caused by underactivation of glutamate receptors. Phencyclidine (PCP) is a psychotomimetic, producing both positive and negative symptoms of schizophrenia.

32 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry PCP acts as a NMDA receptor antagonist, and prevents glutamate from acting normally. When NMDA receptor underactivation is prolonged over long periods, symptoms ranging from memory loss to acute schizophrenia emerge.

33 Figure The Effects of PCP on the NMDA Receptor (Part 1)

34 Figure The Effects of PCP on the NMDA Receptor (Part 2)

35 16 Schizophrenia Is the Major Neurobiological Challenge in Psychiatry An integrative model suggests that schizophrenia will develop if a compromised brain is exposed to environmental stressors. Examples are stresses of city life, prenatal exposure to influenza, and loss of oxygen at birth.

36 Figure A Model of the Interaction of Stress and Brain Abnormalities in Schizophrenia

37 16 Mood Disorders Are a Major Psychiatric Category Depression most common mood disorder, characterized by: Unhappy mood Loss of interest, energy, and appetite Difficulty in concentration Restless agitation

38 16 Mood Disorders Are a Major Psychiatric Category Unipolar depression depression that alternates with normal emotional states Depression may last for several months. Inheritance is a factor in depression.

39 16 Mood Disorders Are a Major Psychiatric Category Brain changes with depression: Increased blood flow to the frontal cortex and amygdala Decreased blood flow to areas involving attention and language ( 認知區域 )

40 Figure Brain Activity Patterns in Depression

41 16 Mood Disorders Are a Major Psychiatric Category Neurochemical theories of depression: The monoamine hypothesis suggests depression is caused by reduced synaptic activity of norepinephrine and serotonin Monoamine oxidase (MAO) is an enzyme that inactivates monoamines.

42 16 Mood Disorders Are a Major Psychiatric Category Treatment with monoamine oxidase (MAO) inhibitors raises the level of monoamines at the synapse. (MAOI ~ antidepressant) Reserpine, a drug which reduces monoamines in the brain, can cause depression.

43 16 Mood Disorders Are a Major Psychiatric Category Electroconvulsive shock therapy (ECT) induction of a seizure ECT induces release of monoamines. Transcranial magnetic stimulation (TMS) appears to alter the metabolism of monoamine transmitters.

44 16 Mood Disorders Are a Major Psychiatric Category Serotonin deficiency is important in depression. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block the reuptake of serotonin at synapses.

45 16 Mood Disorders Are a Major Psychiatric Category Problems with theory of serotonin reduction as a cause of depression: Long lag time between treatment and reduction of symptoms Not everyone is cured, or even helped SSRIs increase risk of suicide in children and adolescents

46 16 Mood Disorders Are a Major Psychiatric Category People with Cushing s syndrome have high levels of glucocorticoids and are prone to depression. Symptoms of depression, obesity, and body hair suggest dysfunction of the hypothalamic pituitary adrenal axis.

47 Figure The Hypothalamic Pituitary Adrenal Axis in Depression (Part 1)

48 Figure The Hypothalamic Pituitary Adrenal Axis in Depression (Part 4)

49 16 Mood Disorders Are a Major Psychiatric Category The dexamethasone suppression test can show excess cortisol release seen in suicide victims and depressed patients. Dexamethasone, a synthetic glucocorticoid, can suppress cortisol release in normal people, but not in depressed patients.

50 Figure The Hypothalamic Pituitary Adrenal Axis in Depression (Part 2)

51 Figure The Hypothalamic Pituitary Adrenal Axis in Depression (Part 3)

52 16 Mood Disorders Are a Major Psychiatric Category More women than men suffer from depression. May reflect patterns of help-seeking May have a psychosocial explanation, such as social discrimination Gender differences in endocrine physiology

53 16 Mood Disorders Are a Major Psychiatric Category Sleep is altered by depression. Stages 3 and 4 of slow-wave sleep are reduced. Patients enter REM sleep very quickly, with an increase of REM sleep in the first half of the night. Suppressing REM sleep may help with depression.

54 Figure Sleep and Depression (Part 1)

55 Figure Sleep and Depression (Part 2)

56 16 Mood Disorders Are a Major Psychiatric Category Seasonal affective disorder (SAD) is a type of depression brought on by the shorter days of winter. Phototherapy administered in the morning can suppress melatonin, a hormone that may be important in controlling sleep. SAD may also respond to SSRIs.

57 16 Mood Disorders Are a Major Psychiatric Category Animal models can help study depression. In learned helplessness, an animal is exposed to a repetitive stressful stimulus. Learned helplessness is also linked to a decrease in serotonin function. giving up depression Antidepressants reverse it.

58 16 Mood Disorders Are a Major Psychiatric Category Bipolar disorder is characterized by periods of depression alternating with expansive mood, or mania. The rate of cycling varies rapid cycling consists of four or more cycles in one year. Some individuals may cycle several times in one day.

59 16 Mood Disorders Are a Major Psychiatric Category Cyclothymia, a milder form of bipolar disorder patients cycle between dysthymia (mild depression) and hypomania (increased energy). Lithium is a mood-stabilizing drug used to treat bipolar disorder it seems to interact with the circadian clock.

60 Figure Functional Images of Bipolar Disorder

61 16 There Are Several Types of Anxiety Disorders Phobic disorders intense irrational fears centered on an object, activity, or situation that a person avoids Anxiety disorders: panic disorder recurrent attacks of intense fearfulness; and generalized anxiety disorder persistent, excessive anxiety, and worry

62 16 There Are Several Types of Anxiety Disorders Benzodiazepines are anxiolytic drugs used to treat anxiety. They bind to GABA receptors and enhance GABA s inhibitory actions. Serotonin agonists and SSRIs are also used to treat anxiety.

63 Figure The Distribution of Benzodiazepine Receptors in the Human Brain

64 16 There Are Several Types of Anxiety Disorders In posttraumatic stress disorder (PTSD), unpleasant memories repeatedly plague the victim. PTSD victims show: Memory changes, such as amnesia Flashbacks Deficits in short-term memory

65 16 There Are Several Types of Anxiety Disorders PTSD victims have decreased volume in the right hippocampus may be a risk factor rather than a consequence. Fear conditioning is learning in which fear is associated with a neutral stimulus.

66 16 There Are Several Types of Anxiety Disorders Persistent memories and fears in PTSD may be a failure to forget. Projections to the amygdala may lose effectiveness in suppressing fear. PTSD victims may have an increased response to stress hormones.

67 Figure A Neural Model of Posttraumatic Stress Disorder

68 16 There Are Several Types of Anxiety Disorders Obsessive compulsive disorder (OCD) is marked by recurring, repetitive acts. In OCD patients: Routine acts become compulsions Recurrent thoughts become obsessions

69 16 There Are Several Types of Anxiety Disorders Serotonin plays a major role in OCD, in the orbitofrontal prefrontal cortex. OCD is heritable, and may also be triggered by infections. OCD is often co-morbid with Tourette s syndrome they occur together.

70 16 There Are Several Types of Anxiety Disorders OCD and Tourette s syndrome involve disorders of the basal ganglia. Drug therapy in Tourette s syndrome has focused on dopamine rather than serotonin. D 2 receptors are denser in the caudate nucleus of a Tourette s sufferer.

71 Box 16.3 Tics, Twitches, and Snorts: The Unusual Character of Tourette s Syndrome

72 16 Neurosurgery Has Been Used to Treat Psychiatric Disorders Psychosurgery uses brain lesions to modify severe psychiatric disorders. Lobotomy disconnects parts of the frontal lobe from the rest of the brain. More localized lesions have proven more effective.

73 16 Neurosurgery Has Been Used to Treat Psychiatric Disorders Cingulotomy lesions of the cingulate cortex to treat anxiety, depression, and OCD Capsulotomy lesions of the internal capsule, to treat anxiety disorders Deep brain stimulation through implanted electrodes can be effective.

74 Figure Neurosurgery to Treat Obsessive Compulsive Disorder (Part 1)

75 Figure Neurosurgery to Treat Obsessive Compulsive Disorder (Part 2)

76 16 Abnormal Prion Proteins Destroy the Brain Prions abnormally folded proteins that lead to brain degeneration Scrapie a fatal disease in sheep, caused by prions

77 16 Abnormal Prion Proteins Destroy the Brain Bovine spongiform encephalopathy (BSE, or mad cow disease) the bovine form of scrapie Creutzfeldt Jakob disease (CJD) the human disorder, causing dementia, sleep disorders, schizophrenia-like symptoms, and death

78 Figure The Culprits of Mad Cow Disease

Νευροφυσιολογία και Αισθήσεις

Biomedical Imaging & Applied Optics University of Cyprus Νευροφυσιολογία και Αισθήσεις Διάλεξη 19 Ψυχασθένειες (Mental Illness) Introduction Neurology Branch of medicine concerned with the diagnosis and