Schizophrenia

Schizophrenia, ICD, DSM, Antipsychotics

1. Dr. Nidhi Sharma

2. CONTENT Dr. Nidhi Sharma 23-Jun-21 Introduction Epidemiology Classification Signs and symptoms Pathophysiology Diagnosis Complications Management Prognosis Clinical Research Landmark Studies

3. Introduction Schizophrenia is a serious mental illness that interferes with a person’s ability to think clearly, manage emotions, make decisions and relate to others. Schizophrenia literally means “Split Mind”. (Schizein means , " to split“ and phrēn means " mind") Schizophrenia is among the most disabling and economically catastrophic medical disorders Earliest case of schizophrenia - James Tilly Matthews (1809) The first, formal description of schizophrenia as a mental illness was made in 1887 by Dr. Emile Kraepelin . He used the term "dementia praecox" to describe the symptoms now known as schizophrenia.

4. Introduction The term “schizophrenia” was coined on April 24, 1908, by Professor Paul Eugene Bleuler . He suggested that dementia praecox was associated with neither dementia nor precociousness, and emphasized that splitting of psychic functioning is an essential feature of schizophrenia In 2002, new name was given to Schizophrenia - Integration Disorder It refers to a person’s inability to process information about their environment, which may cause them to experience confusion about what is imagined and what is real.

5. James Tilly Matthews A former peace activist of the Napoleonic Wars who was confined to London's notorious Bedlam asylum in 1797 for believing that his mind was under the control of the "Air Loom" - a terrifying machine whose rays and gases were brainwashing politicians and plunging Europe into revolution, terror, and war.

6. Epidemiology Incidence - 1.5 per 10,000 people Prevalence – 1% Age of onset: Men: Between 18 and 25 Women: Between 25 and 35 Schizophrenia is diagnosed 1.4 times more frequently in males than females Schizophrenia is associated with an average of 14.5 years of potential life lost. The loss was greater for men (15.9) than for women (13.6). Life expectancy was greatly reduced in patients with schizophrenia, at 64.7 years (59.9 for men and 67.6 for women).

7. DSM Criteria/Symptoms Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): Positive Symptoms   Delusions: A belief or altered reality that is persistently held despite evidence or agreement to the contrary Erotomanic Grandiose Persecutory Jealous Somatic

8. DSM Criteria/Symptoms Hallucinations: Sensory experiences that appear real but are created by your mind Visual Olfactory Gustatory Auditory Tactile Disorganized speech (e.g., frequent derailment or incoherence )   Grossly disorganized or catatonic behavior

9. DSM Criteria/Symptoms Negative Symptoms Affective flattening: A loss or lack of emotional expressiveness Alogia: Lack of speech Avolition: Lack of motivation that makes it hard to get anything done

10. Classification ICD-10 Description DSM-IV Paranoid  (F20.0) Delusions and hallucinations are present but thought disorder, disorganized behavior, and affective flattening are not prominent. Paranoid (295.3) Hebephrenic  (F20.1) Thought disorder and flat affect are present together. Disorganized (295.1) Catatonic  (F20.2) Psychomotor disturbances are dominant features. Symptoms can include catatonic stupor and waxy flexibility. Catatonic (295.2) Undifferentiated  (F20.3) Psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic types have not been met. Undifferentiated (295.9) Post-schizophrenic depression  (F20.4) A depressive episode arising in the aftermath of a schizophrenic illness where some low-level schizophrenic symptoms may still be present. Not present Residual  (F20.5) Positive symptoms are present at a low intensity and negative symptoms are prominent. Residual (295.6) Simple  (F20.6) Delusions and hallucinations are not evident and negative symptoms progress slowly. Not present

11. Phases

12. Louis Wain’s Cat Illustrations

13. Pathophysiology Genetics Physical changes in brain Chemical changes in brain (Neurotransmitters) Pregnancy or birth complications Childhood trauma

14. Genetics Chromosome no. 1, 5, 6, 8, 11, 12 & 22 Neuregulin – 1 Protein Deletion of a region on chromosome 22 (22q11.2-deletion syndrome) increases the risk of developing schizophrenia approximately 30-fold in humans.

15. Genetics

16. Physical changes in brain Enlarged ventricles. Schizophrenia cases exhibited progressive brain reductions mainly in the prefrontal cortex and temporal lobes. Localized gray matter volume reduction of the left temporal lobe. The size of the volume reduction in superior temporal gyrus is related to the degree of thought disorder and hallucination. In schizophrenic patients with AVH (auditory verbal hallucinations), the left middle temporal gyrus was found significantly thinner than in patients without AVHs. The temporal and the occipital lobe white matter shortfall can also exacerbate the chances of acquiring schizophrenia.

17. Chemical changes in brain Dopamine Hypothesis Serotonin Hypothesis Glutamate Hypothesis GABA Hypothesis

18. Dopamine Hypothesis Earlier Version: In Schizophrenic patients, neurons that uses Dopamine, fire too often and transmit too many messages. Revised Version: Hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic brain regions contributes to positive symptoms of schizophrenia Negative and cognitive symptoms of the disorder can be attributed to hypofunctionality of dopamine D1 receptor neurotransmission in the prefrontal cortex Evidence in support Increased density of the dopamine D2 receptor in postmortem brain tissue of schizophrenia sufferers Dopamine-releasing drugs, such as amphetamine, possess psychotomimetic properties inducing Schizophrenia like symptoms A group of drugs called the phenothiazines, including antipsychotics such as chlorpromazine, has been found to antagonize dopamine binding (particularly at receptors known as D2 dopamine receptors) and reduce positive psychotic symptoms

19. Dopamine Hypothesis Evidence against Some patients had over 90% of their D2 receptors blocked by antipsychotic drugs but showed little reduction in their psychoses, primarily the patients who have had the psychosis for ten to thirty years Although dopamine-inhibiting medications modify dopamine levels within minutes, the associated improvement in patient symptoms is usually not visible for at least several days, suggesting that dopamine may be indirectly responsible for the illness

20. Serotonin Hypothesis Increased level of Serotonin causes Schizophrenia Evidence in support LSD , a 5-HT2 agonist causes hallucination 5HT2A regulates Dopamine release in Mesolimbic system.

21. Pregnancy and Birth Complications Fetal Hypoxia Oxygen deficiency to the tissues of the fetus Risk for later schizophrenia related to fetal hypoxia is restricted to individuals with a family history of psychosis In utero oxygen deprivation has been hypothesized as a mechanism contributing to the anatomical changes in the brain Maternal Infections during Pregnancy or Delivery Exposure to viruses and other infectious agents such as influenza, toxoplasmosis, and herpes simplex virus type 2 during pregnancy and around the time of conception

22. Pregnancy and Birth Complications Fetal malnutrition Shortage of nutrients influences neurodevelopment. Typically, these nutrients exist in the diet as folate (B vitamins), proteins, essential fatty acids, and vitamins A and D. Deficiencies of B vitamins can lead to accumulated high levels of the potentially dangerous amino acid, homocysteine and elevated levels of homocysteine have been found in patients with schizophrenia Hypoxia Infection Malnutrition

23. Childhood Trauma Childhood adversity (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) might be associated with increased risk for psychosis in adulthood Permanent separation from, or death of, one or both parents may lead to psychosis Childhood trauma is believed to be associated with the most severe forms of positive symptomatology in adulthood, particularly hallucinations and affective symptoms

24. Diagnosis Rule out other mental health disorders and determine that symptoms are not due to substance abuse, medication or a medical condition Physical exam to rule out other problems that could be causing symptoms and to check for any related complications Tests to rule out conditions with similar symptoms, and screening for alcohol and drugs. Imaging studies, such as an MRI or CT scan Psychiatric evaluation DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for schizophrenia, published by the American Psychiatric Association

25. Complications Suicide, suicide attempts and thoughts of suicide Anxiety disorders and obsessive-compulsive disorder (OCD) Depression Abuse of alcohol or other drugs, including nicotine Inability to work or attend school Financial problems and homelessness Social isolation Aggressive behavior, although it's uncommon

26. Management Medication Psychosocial Therapy Electroconvulsive Therapy

27. Medication Antipsychotics Ease delusions and hallucinations Act on dopamine and serotonin Can be taken as an oral daily dose or a long-acting injectable antipsychotic medication (LAI) given once or twice a month Work best on "positive" symptoms like hallucinations and delusions Less effective on "negative" symptoms like withdrawal and lack of emotion

28. Medication Mood stabilizers Lamotrigine (Lamictal) Carbamazepine (Tegretol) Valproic acid (Depakote) Antidepressants Citalopram (Celexa) Fluoxetine (Prozac) Paroxetine (Paxil, Pexeva ) Sertraline (Zoloft) Escitalopram (Lexapro)

29. Psychosocial Therapy Cognitive Enhancement Therapy (CET) Assess the symptoms and findings Improve their attention, memory, and ability to organize their thoughts Cognitive Behavioural Therapy (CBT) Establish link between thoughts, feelings, actions & symptoms 5 – 20 sessions Trace the origin of symptoms Challenge the belief and test their validity Give the patient alternate explanation and the coping strategies for their false beliefs Assertive Community Treatment Highly personalized services to help patients meet life’s daily challenges, like taking medications Social Skills Training Improves communication and social interactions

30. Psychosocial Therapy

31. Electroconvulsive Therapy In Catatonic schizophrenia and Acute episode of Schizophrenia Seizures are electrically induced for the therapeutic effect Has proved to be successful when even medication is not effective 3 times a week (20 to 25 treatments) Side Effects: Confusion, Temporary Memory Loss, Heart Complications, Nausea, Vomiting, Headache, Muscle Ache, Jaw Pain, Joint Dislocation, Fractures DEATH may also occur in rare cases

32. Chlorpromazine Classic or Typical Antipsychotic Blocks the postsynaptic dopamine receptors (D2) in cortical and limbic areas of the brain, thereby prevents the excess of dopamine in the brain leading to reduction in positive symptoms, such as hallucinations and delusions Oldest drug used in Schizophrenia Marketed under the brand name Thorazine Dosage: 30-75 mg/day initially; maintenance: usually 200 mg/day (up to 800 mg/day in some patients; some patients may require 1-2 g/day

33. Clozapine 2nd Generation or Atypical Antipsychotic It is mainly a 5-HT2A antagonist improving depression, anxiety, and the negative cognitive symptoms Indicated only in Treatment-Resistant Schizophrenia Reduces the Risk of Recurrent Suicidal Behavior Starting dose is 12.5 mg once daily or twice daily. The total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-tolerated, to achieve a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of 2 weeks.

34. Typical Vs Atypical Adverse effects ARI CPZ CLO HAL OLA PAL RIS Anticholinergic effects ++ +++ ++ Acute parkinsonism + + +++ 0/+ ++ ++ Akathisia ++ + + +++ + + + Tardive dyskinesia 0/+ ++ ++ 0/+ 0/+ 0/+ Diabetes 0/+ +++ +++ 0/+ +++ + + Weight gain 0/+ +++ +++ + +++ ++ ++ Increased lipids 0/+ +++ ++ 0/+ +++ + + Neutropenia 0/+ 0/+ +++ 0/+ 0/+ 0/+ 0/+ Orthostatic hypotension 0/+ ++ ++ + + + Hyperprolactinemia + + ++ + +++ +++ Sedation 0/+ ++ +++ + +/++ 0/+ + Seizures 0/+ 0/+ ++ 0/+ 0/+ 0/+ 0/+

35. Prognosis Developing countries have a larger proportion (50-60%) with a good outcome and lesser percentage with a worst outcome as compared to developed countries Environmental factor plays an important role in prognosis of mild cases but not in severe cases Family h/o schizophrenia indicates a poor prognosis If the schizophrenia onset was precipitating by some events/ factor, the prognosis is regarded as good on the other hand absence of a precipitating factor indicates poor outcome Male gender, insidious onset, lesser social support, low level of employment predict a poor outcome Being married, female gender, better premorbid adjustment, no drug use, acute onset, short duration of illness and short duration of untreated illness – better outcome High level of Expressed Emotion (EE) is associated significantly with high rate of relapse and poor outcome

36. Clinical Research 1960 1970 1980 1990 2000 2010 Etiology Epidemiology Epidemiology Epidemiology _ Epidemiology _ Biological Research Biological Research Biological Research Biological Research Biological Research Clinical aspects Phenomenology Phenomenology Phenomenology Phenomenology Phenomenology _ _ Psychological Psychological Psychological _ _ _ Psychosocial Psychosocial Psychosocial Psychosocial Treatment Treatment Treatment Treatment Treatment Treatment Course & Outcome Course & Outcome Course & Outcome Course & Outcome Course & Outcome _ _ _ Rehabilitation Rehabilitation Rehabilitation _

37. Landmark Studies International Pilot Study of Schizophrenia (IPSS) – Agra: Baseline, 2 Years and 5 Years of F/U Determinants of Outcome of Severe Mental Disorders ( DOSMeD ) – Agra, Chandigarh – 1 Year and 2 Years of F/U International Study of Schizophrenia ( ISoS ) – 15 Years F/U of DOSMeD & RAPyD and 25 Years F/U of IPSS ICMR Project (Vellore, Madras, Lucknow) – 2 Years F/U IPSS Agra Cohort – 13 to 14 Years of F/U of IPSS Madras longitudinal study – 10 Years F/U of ICMR Chandigarh Cohort – 15 Years F/U of DOSMeD

38. Landmark Studies Name Acronym Indian Centers Follow-Up Period International Pilot Study of Schizophrenia IPSS Agra Baseline 2 Years 5 Years Determinants of Outcome of Severe Mental Disorders DOSMeD Agra Chandigarh 1 Year 2 Years International Study of Schizophrenia ISoS Agra Chandigarh IPSS – 15 Years DOSMeD – 25 Years Study of Factors Associated with Course and Outcome of Schizophrenia (ICMR) SOFACOS Madras Lucknow Vellore 2 Years IPSS Agra Cohort _ Agra IPSS – 13 to 14 Years Madras Longitudinal Study _ Madras SOFACOS – 10 Years Chandigarh Cohort _ Chandigarh DOSMeD – 15 Years

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