Understanding Schizophrenia: Symptoms, Causes, and Treatments

1. Chapter 15 The Biological Basis of Affective Disorders and Schizophrenia

2. Schizophrenia • First described in 1883 by Emil Kraepelin – dementia praecox, premature insanity • The Swiss psychiatrist, Eugen Bleuler, coined the term, "schizophrenia" in 1911. He was also the first to describe the symptoms as "positive" or "negative." • Bleuler renamed it schizophrenia for three reasons: • The deteriorization doesn’t always begin in adolescence, it can begin later in life • Mental functioning may actually improve rather than deteriorate after it is diagnosed • The disorder seems to reflect a splitting of the psyche’s functions: emotion and perception

4. Schizophrenia: a definition • Mental disorder characterized by loss of contact with reality; disturbances in perception, emotion, cognition, motor behavior. • Characterized by positive, negative, and cognitive symptoms: • Positive Symptoms - Behaviors exhibited by a person with schizophrenia but absent in people without the disorder • Negative Symptoms - Normal behaviors that are absent in people with schizophrenia • Cognitive Symptoms – Deficits in learning, reasoning or perception

5. Positive Symptoms • Thought disorders - tangentiality, neologisms, loosening of associations, word salad, rambling monologues • Delusions – grandeur, persecution, control • Hallucinations – visual, tactile, auditory, olfactory, gustatory • Movement - high levels of motor excitement, catatonic behaviors, repetitive motor activities

6. Hieronymus Bosch (1450 – 1516)

7. Negative Symptoms • Disturbances in affect - blunted or flat affect • Lack of interest in life, low motivation • Anhedonia – inability to experience pleasure • Social withdrawal or emotional detachment • Low energy • Alogia – poverty of speech • Inappropriate social skills or lack of interest or ability to socialize with other people • Inability to make friends or keep friends, or not caring to have friends

8. Cognitive Symptoms • Disorganized thinking • Slow thinking • Difficulty sustaining attention • Difficulty understanding • Poor concentration and problem solving • Poor memory • Difficulty expressing thoughts • Difficulty integrating thoughts, feelings and behavior

9. Course of Schizophrenia • Prodromal phase - The phase which the person becomes socially withdrawn and school or work performance declines. • Active phase -The phase in which the more acute symptoms of the disorder appear, such as hallucinations and delusions. • Residual phase - The phase in which some recovery of functioning occurs.

10. Schizophrenia: The Dopamine Hypothesis and Drug Treatments • Dopamine hypothesis of schizophrenia -The view that an excess of activity in the dopamine system results in the positive symptoms of schizophrenia. • Chlorpromazine (a DA antagonist) blocks postsynaptic DA receptors and improves positive symptoms in schizophrenics. • Therapeutic effectiveness is directly related to the ability to bind tightly to the receptors

11. Schizophrenia: Chlorpromazine’s Synaptic Effect

12. Clinical Potency of Antipsychotic Drugs

13. Schizophrenia: Drug Treatments • Effect of DA agonists • Amphetamine and cocaine produce positive symptoms of schizophrenia. • Amphetamine use exacerbates positive symptoms in people already diagnosed with schizophrenia. • L-Dopa (used to treat Parkinson’s) is a DA agonist which can induce a psychosis which is responsive to clozapine.

14. Evidence Against a DA Hypothesis of Schizophrenia • Approximately 30% of people with schizophrenia do not experience relief of positive symptoms with DA antagonists. • There are also lower levels of GABA and glutamate in brains of people with schizophrenia. Some studies suggest the NMDA receptor may be involved.

15. Problems with DA Antagonists • Tardive dyskinesia - A motor disorder with facial tics and involuntary limb movements; often appears after long-term use • Relief from negative symptoms is not experienced with DA antagonists • A new family of antipsychotic drugs, which block D4 receptors, relieve positive and negative symptoms without causing tardive dyskinesia • A hypothesis of brain damage may explain the negative symptoms

16. Brain Damage and Schizophrenia • Lateral ventricles of many people are enlarged. • Loss of dendritic material in the prefrontal cortex. • Reduced numbers of neurons in the thalamus and hippocampus. • Hippocampus connections with the prefrontal cortex are connected in a more disorganized fashion than normal.

17. Possible Causes of Brain Abnormalities • Epidemiological studies • Season of birth • Viral epidemics • Population density • Vitamin D deficiency • Prenatal malnutrition • Substance abuse • Complications of pregnancy and childbirth • Fetal growth retardation • Hypoxia • Rh factor incompatability

18. Viral Infection and Schizophrenia

19. Hypofrontality Theory • Theory that the negative symptoms of schizophrenia are caused by decreased activity in the prefrontal cortex. • PET scans show decreased activity in the frontal area of the brain • People with schizophrenia have difficulty with tasks requiring working memory. • Metabolic hypofrontality in people with schizophrenia can be reversed with DA agonists but at what cost? • Third generation antipsychotic – partial agonist • Some people do not exhibit hypofrontality, so results are mixed with regard to this theory.

20. Role of Genetics • What is inherited is only a susceptibility or genetic predisposition to develop schizophrenia. • The concordance rate for identical twins is not 100% but about 50% indicating that a particular gene is not by itself sufficient to produce schizophrenia. • No single gene for schizophrenia • Children of older fathers • Epigenetic influences inhibit or promote gene expression

21. Schizophrenia: No Definitive Explanations • Neither the DA theory nor the hypofrontality theory provide a complete explanation. • Several brain structures are dysfunctional and act together to produce symptoms. • Schizophrenia may be several related disorders rather than a single disorder • Some patients have prefrontal dysfunctions, others do not • DA antagonists help some patients but not others. • What role, if any, does puberty play • Much more research is necessary