Schizophrenia pathophysiology
- 2. Contents • Definiton • Types of Schizophrenia • Epidemiology • Symptoms • Etiology • Patho-physiology • Diagnosis • Drug Therapy
- 3. Schizophrenia is a chronic heterogeneous syndrome of disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, cognitive deficits, and impaired psychosocial functioning
- 4. • It is a psychotic disorder marked by severely impaired thinking, emotions and behaviours. Schizophrenic patients are unable to filter sensory stimuli and may have enhanced perception of sounds, colours and other features of their environment. • Most schizophrenics, if untreated can gradually withdraw themselves from the interactions with other people and lose their ability to take care of personnel needs
- 5. TYPES OF SCHIZOPHRENIA CATATONIC Motor symptoms are most notable. The patient may either demonstrate rigid immobility or excessive purposeless movement. The patient may be silent and withdrawn or may become loud and shout. Bizarre voluntary movements such as posturing may also occur. The patient may fluctuate between the two extremes. DISORGANISED The patient tends to have disorganized speech and behavior with a fl at affect. Hallucinations and delusions are not well formed and fragmented. The patient may also have bizarre mannerisms and grimacing.
- 6. PARANOID The most common type of schizophrenia. Patients are usually preoccupied with paranoid delusions or auditory hallucinations. Cognitive function is usually preserved; if thought disorder is present, it does not prevent description of delusions or hallucinations. RESIDUAL The patient does not have acute psychosis, but some symptoms of schizophrenia remain. Largely negative symptoms are seen, such as flat affect, social withdrawal, and loose associations. Prominent delusions or hallucinations are not present.
- 7. UNDIFFERENTIATED The patient meets the criteria for a diagnosis of schizophrenia but does not meet the criteria for a specific type, or the patient may meet the criteria for multiple types of schizophrenia. No one type appears to be dominant.
- 8. EPIDEMIOLOGY Lifetime prevalence of schizophrenia ranges from 0.6% to 1.9%, with an average of approximately 1%. The worldwide prevalence of schizophrenia is remarkably similar among all cultures. Schizophrenia most commonly has its onset in late adolescence or early adulthood and rarely occurs before adolescence or after the age of 40 years. The prevalence of schizophrenia is equal in males and females.
- 9. SYMPTOMS OF SCHIZOPHRENIA POSITIVE SYMPTOMS DELUSION HALLUCINATION COMBATIVENESS INSOMNIA NEGATIVE SYMPTOMS Affective flattening Alogia Anhedonia Amotivation Apathy Asocial behavior DISORGANIZED SYMPTOMS Disorganized speech Thought disorder Disorganized behavior Poor attention
- 10. ETIOLOGY • No one knows the exact causes of Schizophrenia, but multiple possible factors have been discovered. • These factors include: 1. Genetics 2. Brain chemical imbalance 3. Environmental factors 4. Family history
- 11. PATHOPHYSIOLOGY Genetic Theory: • A strong genetic link exists for the development of schizophrenia. Occurs in 1% of general population, however this increases to 10% if a 1st degree relative has a history of schizophrenia. Risk of developing schizophrenia further increases to 40% when both parents have a history of schizophrenia. Studies are going to locate specific genes to the development of schizophrenia.
- 12. Dopamine Theory: • The dopamine hyperactivity in the brain is responsible for psychotic symptoms present in schizophrenia. While dopamine hyperactivity is present in mesolimbic pathway, other areas of the brain such as the prefrontal, frontal and temporal cortices have decrease activity during acute psychosis. Other neurotransmitters thought to be involved in schizophrenia include 5-HT, glutamate. The role of glutamate is also being evaluated because one of its major functions is to regulate dopamine activity. Glutamate deficiency has been found to cause similar effects to that of dopamine hyperactivity.
- 13. Neuro-developmental Theory: • Schizophrenia occurs as a result of an in Utero disturbance during pregnancy. Potential causes of this disturbance include upper respiratory infection, obstetric complication and neonatal hypoxia.
- 14. Psychosocial Theories: • These theories propose that situation such as stress, poor interpersonal skills, conflicting family, communication and various socio-economic influences are linked to development of schizophrenia.
- 15. Neurotransmitter Abnormalities • Abnormalities in the dopaminergic system – Hypo-dopaminergic activity in the mesocortical system, leading to negative symptoms – Hyper-dopaminergic activity in the mesolimbic system, leading to positive symptoms
- 17. • The Diagnostic and Statistical Manual of Mental Disorders, specifies the following criteria for the diagnosis of schizophrenia: ✓ Persistent dysfunction lasting longer than 6 months ✓ Two or more symptoms (present for at least 1 month), including hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms ✓ Significantly impaired functioning (work, interpersonal, or self-care) DIAGNOSIS
- 18. • Schizophrenic patients appear to have small brains with large ventricular volumes, indicating a relative deficit of neurons. • Structural and functional brain imaging studies have strongly suggested that regions of the medial temporal lobe (e.g., hippocampus) have diminished numbers of neurons and also have demonstrated the inability of individuals with schizophrenia to activate the frontal cortex and successfully execute tasks that require frontal cortical function. IMAGING Ventricular enlargement and cortical atrophy, as seen on CT scan, have been correlated with chronic course, severe cognitive impairment, and non responsiveness to neuroleptic medications. Decreased frontal lobe activity seen on PET scan has been associated with negative symptoms.
- 20. TREATMENT GOALS AND OBJECTIVES: There is currently no known cure for schizophrenia. Treatment options include psychotherapy as well as pharmacotherapy. The goals and objectives of treatment are as follows: A. Minimize symptoms of schizophrenia B. Improve quality of life and social/occupational functioning C. Prevent relapse and hospitalization D. Minimize adverse effects of medications E. Prevent suicide attempts or self-harm
- 22. PHARMACOLOGICAL TREATMENT • Antipsychotic medications: Two generation of antipsychotic medications are available for treatment: 1. First generation or typical antipsychotics 2. Second Generation or Atypical Antipsychotics:
- 23. First generation or typical antipsychotics: Chlorpromazine Trifluperazine Thioridazine Perphanazine Fluphenazine Haloperidol Loxapine
- 24. • Mechanism of Action: The antipsychotic effect of these medications is primarily mediated through the blockade of dopamine type 2 (D2 receptors). Adverse effects: Sedation, anticholinergic effects, EPS hyperprolactemia, moderate weight gain Photosensitivity
- 25. Second Generation or Atypical Antipsychotics Clonazapine Risperidone Olanzapine Quetipine Ziprasidone
- 26. • Mechanism of action: Atypical antipsychotics are dopamine antagonists but also block 5-HT2A-receptors Adverse effects: Sedation, anticholinergic effects (Clonazapine, Olanzapine), EPS, DM, hyperprolactemia (Risperidone), hypercholestremia
- 27. References 1. Text book of Clinical Pharmacy and Therapeutics 2. Text book of Pharmacology by RANG and DALE’S. 3. Essentials of Medical Pharmacology by K.D.Tripathi.