Schizophrenia and schizophrenia-like disorders

1. Schizophrenia and schizophrenia-like disorders Dr: Alex Fish (Shaohua Yu) E-mail:yushonline@aliyun.com The Second Affiliated Hospital Zhejiang University College of Medicine

2. A beautiful mind John Forbes Nash A professor of Princeton University A mathematical genius He made an astonishing discovery early in his career and stood on the brink of international acclaim. But Nash soon found himself on a painful journey of self-discovery once he was diagnosed with schizophrenia After years of medication and struggle, he eventually triumphed over this tragedy, and finally, late in life, received the Nobel Prize.

3. Category of psychotic disorders Schizophrenia (SC) Schizoaffective disorder Schizophreniform disorder Brief psychotic disorder Delusional disorder

4. Introduction • The definition of schizophrenia • The symptom of schizophrenia • Diagnostic criteria of schizophrenia (DSM-V and ICD-10) • The etiology and pathogenesis of schizophrenia • The therapeutic principle of schizophrenia • The factors influencing prognosis of schizophrenia • The concept and diagnostic significance of insight

5. Definition of SC Schizophrenia is a disorder characterized by apathy, absence of initiative (avolition), and affectiveblunting. Patients have alterations in thoughts, perceptions, mood, and behavior. Many schizophrenics display delusions, hallucinations and misinterpretations of reality. • “Schizophrenia” – split mind • Multiple personality disorder is not schizophrenia

6. Epidemiology — gender and age SC is equally prevalent in men and women. Onset in men is usually earlier (15-24) than in women (25-34) It's uncommon for children to be diagnosed with SC and rare for those older than 40. Lifetime prevalence of about 1%

7. Clinical feature of Schizophrenia 3 4 Mood symptoms Cognitive impairment 1 2 Positive symptoms Negative symptoms

8. Positive Symptoms Those that appear to reflect an excess or distortion of normal functions.

9. Positive Symptoms Delusions. Those where the patient thinks he is being followed or watched are common; also the belief that people on TV, radio are directing special messages to him/her.

10. Positive Symptoms Hallucinations. Distortions or exaggerations of perception in any of the senses. Often they hear voices within their own thoughts followed by visual hallucinations.

11. Positive Symptoms Disorganized thinking/speech. Loose associations; speech is tangential, loosely associated or incoherent enough to impair communication.

12. Positive Symptom Grossly disorganized behavior. Difficulty in goal directed behavior, unpredictable agitation or silliness, social disinhibition, or bizarre behavior. There is a purposelessness to behavior.

13. Positive Symptom Catatonic behavior. Marked decrease in reaction to immediate environment, sometimes just unaware of surroundings, rigid or bizarre postures, aimless motor activity.

14. Other Positive Symptoms • Inappropriate response to stimuli • Unusual motor behavior (pacing, rocking) • Depersonalization • Derealization • Somatic preoccupations

15. Summary of Positive Symptoms Delusions Hallucinations Disorganized thinking Disorganized behavior Catatonic behavior Inappropriate responses

16. FYI: Positive Symptoms Positive symptoms are those that have a positive reaction from some treatment. In other words, positive symptoms respond to treatment.

17. Negative Symptoms Those that appear to reflect a diminution or loss of normal functions. May be difficult to evaluate because they are not as grossly abnormal as positive symptoms.

18. Negative Symptoms Affective flattening. Reduction in the range and intensity of emotional expression, including facial expression, voice tone, eye contact and body language.

19. Negative Symptom Alogia (poverty of speech) Lessening of speech fluency and productivity, thought to reflect slowing or blocked thoughts; often manifested as short, empty replies to questions.

20. Negative Symptom Avolition The reduction, difficulty or inability to initiate and persist in goal-directed behavior. Often mistaken for apparent disinterest.

21. Examples of Avolition No longer interested in going out with friends No longer interested in activities that the person used to show enthusiasm No longer interested in anything Sitting in the house for hours or days doing nothing

22. Disorganized Symptoms This one is somewhat new and may not be considered valid. It is thought disorder, confusion, disorientation and memory problems.

23. Summary of Negative Symptoms Lack of emotion Low energy Lack of interest in life Affective flattening Alogia Inappropriate social skills Inability to make friends Social isolation

24. Mood symptoms Common and severe Depression or mood swings People with schizophrenia often seem inappropriate and odd, causing others to avoid them, which leads to social isolation

25. Cognitive impairment • Exhibit subtle cognitive dysfunction in the domains of attention, executive function, working memory, and episodic memory • The cognitive impairment seems already to be present when patients have their first episode and appears largely to remain stable over the course of early illness

26. Classification of schizophrenia A – paranoid type schizophrenia B – disorganized type schizophrenia C – catatonic type schizophrenia D – undifferentiated type schizophrenia E – residual type schizophrenia

27. Paranoid type schizophrenia • Characterized by preoccupation with one or more delusions or frequent auditory hallucinations • No prominent disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect • Best prognosis

28. Disorganized type schizophrenia • Characterized by prominent disorganized speech, disorganized behavior, and flat or inappropriate affect • worse prognosis

29. Catatonic type schizophrenia Characterized by at least 2 of the following: • Motoric immobility • Excessive motor activity • Extreme negativism or mutism • Peculiar voluntary movements such as bizarre posturing • Echolalia or echopraxia

30. Undifferentiated type schizophrenia Meets criteria for SC, but can not be Characterized by paranoid, disorganized, or catatonic type

31. DSM-V diagnostic criteria for schizophrenia • Two (or more) of the following symptoms present for one month, at least one of these must be (1),(2), or (3): 1.Delusions 2.hallucinations 3.disorganized speech 4.grossly disorganized or catatonic behavior 5.negative symptoms B. Decline in social and/or occupational functioning since the onset of illness C. Continuous signs of illness for at least six months with at least one month of active symptoms

32. DSM-V diagnostic criteria for schizophrenia D. Schizoaffective disorder and mood disorder with psychotic features have been excluded E. The disturbance is not due to substance abuse or a medical condition F. If history of autistic disorder or pervasive developmental disorder is present, schizophrenia may be diagnosed only if prominent delusions or hallucinations have been present for one month

33. ICD-10 diagnositic criteria for schizophrenia 1. At least one of the following: Thought echo, insertion, withdrawal, or broadcasting. Delusions of control, influence, or passivity; clearly referred to body or limb movements or specific thoughts, actions, or sensations; and delusional perception. Hallucinatory voices giving a running commentary on the patient's behavior or discussing him/her between themselves, or other types of hallucinatory voices coming from some part of the body. Persistent delusions of other kinds that are culturally inappropriate or implausible, (e.g. religious/political identity, superhuman powers and ability).

34. 2. Or, at least two of the following: Persistent hallucinations in any modality, when accompanied by fleeting or half-formed delusions without clear affective content, persistent over-valued ideas, or occurring every day for weeks or months on end. Breaks of interpolations in the train of thought, resulting in incoherence or irrelevant speech or neologisms. Catatonic behavior such as excitement, posturing, or waxy flexibility, negativism, mutism, and stupor. Negative symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses. A significant and consistent change in the overall quality of some aspects of personal behavior, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal. ICD-10 diagnositic criteria for schizophrenia

35. Differential Diagnosis PSYCHOSIS Mood disorders Substance induced “organic” mental disorders “Functional” disorders Delirium Dementia Amnestic d/o Schizophrenia “spectrum” disorders

36. Differential Diagnosis Medical/surgical/ substance-induced Psychotic d/o due to GMC Dementias Delirium Medications Substance induced Amphetamines Cocaine Withdrawal states Hallucinogens Alcohol Mood disorders Bipolar disorder Major depression with psychotic features

37. Differential Diagnoses: (Cont) • Personality disorders Schizoid Schizotypal Paranoid Borderline Antisocial • Miscellaneous PTSD Dissociative disorders Malingering Culturally specific phenomena: Religious experiences Meditative states Belief in UFO’s, etc

38. Workup of New-Onset Psychosis:“Round up the usual suspects” Metabolic panel CBC with diff B12, Folate RPR, VDRL Serum Alcohol Urinalysis Thyroid profile URINE DRUG SCREEN!!! CSF/LP HIV serology CT or MRI EEG Good clinical history Physical exam, ROS Labs/Diagnostic tests:

39. Differential diagnosis with SC • Psychotic disorder due to a general medical condition CNS infections, lupus, multiple strokes, HIV … • Substance-induced psychotic disorder Amphetamines, cocaine, phencyclidine(PCP) … • Mood disorder with psychotic features

40. Etiology of SC Genetic factors Biochemical factors Neuropathology Neural circuits Psychoneuroimmunology Psychoneuroendocrinology ……

41. Genetic factors:(The evidence mounts…) Monozygotic twins (31%-78%) vs dizygotic twins 4-9% risk in first degree relatives of schizophrenics Adoption studies Linkage, molecular studies

43. Genetics of Schizophrenia:The take-home message Vulnerability to schizophrenia is likely inherited “Heritability” is probably 60-90% Schizophrenia probably involves dysfunction of many genes

44. Anatomical abnormalities Enlargement of lateral ventricles Smaller than normal total brain volume Cortical atrophy Widening of third ventricle Smaller hippocampus

45. Physiologic studies:PET and SPECT Generally normal global cerebral flow Hypofrontality Failure to activate dorsolateral prefrontal cortex (problem-solving, adaptation, coping with changes)

46. Biochemical factors:The dopamine hypothesis All typical antipsychotics block D2 with varying affinities Dopamine agonists can precipitate a psychosis Amphetamines Cocaine L-dopa

47. Dopamine systems Clinical implications Functions Cell bodies Projections

48. Biochemical factors Dopamine hypothesis Serotonin Glutamate Norepinephrine GABA Neuropeptides Acetylcholine and nicotine

49. Dopamine Hypothesis • Genetic aspect • Most think it involves dopamine: • Elevation of D2 monomers, decrease of dimers • Increased release of dopamine • 2x higher • When given amphetamine, 2x more dopamine is released than control

50. Other Hypotheses • Dopamine hypothesis not agreed on by everyone • Some think excitatory amino acids like glutamate could play a role • One type of glutamate receptor, NMDA: NMDA antagonists (ex ketamine) can induce psychotic symptoms in non-schizophrenic patients • Found increase of NMDA receptors in postmortem studies of schizophrenic brains