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Schizophrenia (Symptoms (Positive symptom: Symptom of schizophrenia…
Schizophrenia
Symptoms
Neurological Symptoms:
- Many studies have found evidence of loss of brain tissue in CT and MRI scans of schizophrenic patients
- The most likely cause of the enlarged ventricles is loss of brain tissue
- Although everyone loses some cerebral gray matter as they age, rate of tissue loss is greater in schizophrenic patients, but just during the onset of the disease.
- Schizophrenia is not a neurodegenerative disease. The loss of brain tissue is not ongoing.
- Most patients with schizophrenia also exhibit neurological symptoms that suggest the presence of brain damage, such as poor control of eye movements and unusual facial expressions
- Hypothesis that there’s a problem in neuronal circuits (rather than DNA, etc..) called psychological disease because we cannot tell if someone has it just by looking at the brain without talking to patient
Negative symptom: Symptom of schizophrenia characterized by the absence of behaviors that are normally present:
a flattened emotional response, social withdrawal, anhedonia = lack of affect (emotions), poverty of speech, and reduced motivation = lack of initiative and persistence
Relationship between Positive and Negative Symptoms:
- Role of the Prefrontal Cortex: There is some evidence that suggests that the negative/cognitive symptoms of schizophrenia are result of brain abnormalities (developmental or degenerative), particularly in the prefrontal cortex
- For example, the negative/cognitive symptoms of schizophrenia are similar to those produced by damage to the prefrontal cortex, and schizophrenic patients do poorly on neuropsychological tests that are sensitive to prefrontal damage
- The negative symptoms of schizophrenia may be caused by hypofrontality, which is decreased activity of the frontal lobes—in particular, of dorsolateral prefrontal cortex (dlPFC)
Hypofrontality
- Decreased activity of the prefrontal
- Believed to be responsible for negative symptoms of schizophrenia
Positive symptom: Symptom of schizophrenia evident by its presence: delusions, hallucinations, or thought disorders
Delusion: belief that is clearly in contradiction to reality
- persecution
- grandeur
- control
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Thought disorder: disorganized, irrational thinking
Cognitive symptom: Symptom of schizophrenia characterized by cognitive difficulties, such as deficits in learning and memory, difficulty in sustaining attention, low psychomotor speed, poor abstract thinking, and poor problem solving
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Psychological Symptoms:
- Symptoms of schizophrenia typically appear gradually and insidiously, over a period of three to five years
Pharmacology
Dopamine Hypothesis:
- Suggests that positive symptoms of schizophrenia are caused by over-activity of dopaminergic synapses, particularly in the striatum (nucleus accumbens).
Mesolimbic dopamine pathway: begins in ventral tegmental area and ends in nucleus accumbens and amygdala,
- Most researchers believe that this pathway is likely to be involved in the positive symptoms of schizophrenia
- Indiscriminate activity of dopaminergic synapses in nucleus accumbens makes it difficult for patients to follow an orderly, rational thought sequence
- Paranoid delusions may be caused by increased activity of dopaminergic input to amygdala
Antipsychotics/Neuroleptics: block dopamine receptors, particularly D2 dopamine receptors --> in order to reduce positive symptoms
Crystal meth/Cocaine: Dopamine agonists. Produce some aspects of the positive symptoms of schizophrenia in people who do not have the disorder
Atypical antipsychotic medications:
- Recently developed medications which reduce positive symptoms and negative symptoms of schizophrenia—even those of many patients who were not significantly helped by older antipsychotic drugs
Clozapine: First of atypical antipsychotic medications joined by several others, including aripiprazole
Ariprazole is a partial dopamine receptor agonist(Partial Agonist = Drug with very high affinity for particular receptor but activates that receptor less than normal ligand does
- Serves as agonist in regions of low concentration of normal ligand and as antagonist in regions of high concentrations)
Evidence for Abnormal Brain Development
- Although symptoms of schizophrenia are not normally seen in childhood, behavioral and anatomical evidence indicates that abnormal prenatal development is associated with schizophrenia
Behavioral: Children who go on to develop schizophrenia display less sociability and deficient psychomotor functioning as kids.
Anatomical: Minor physical abnormalities can be seen in children who go on to develop schizophrenia, such as partial webbing of the two middle toes and a high-steepled palate.
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Heritability:
- Adoption and twin studies provide evidence that schizophrenia is heritable. However, fewer than half the children of parents with chronic schizophrenia become schizophrenic
- So far, no single gene has been shown to cause schizophrenia although researchers have found many candidate genes that appear to increase likelihood of this disease
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Prenatal development
- Concordance rate of identical (monozygotic) twins for schizophrenia is less than 100 percent
- Some investigators indicate that prenatal environment of monozygotic twins is not identical
- There are two types of monozygotic twins: monochorionic (share placenta) and dichorionic (each has its own placenta)
• Prenatal environments of monochorionic twins, who share a single placenta, are more similar than those of dichorionic twins
• The concordance rate for schizophrenia is 60 percent in monochorionic twins and 10.7 percent in dichorionic twins. (so DNA has little to do, but it’s more the environment in the placenta)
• These results provide strong evidence for interaction between heredity and environment during prenatal development
Epidemiological Studies
- Evidence indicates that incidence of schizophrenia is related to several environmental factors that could affect development in utero: season of birth, viral epidemics, population density, and substance abuse
- The seasonality effect:
A disproportionately large number of schizophrenic patients were born in February, March, April, and May
- The number of schizophrenic births in late winter and early spring is especially high if the temperature was lower than normal during previous autumn
- This condition keeps people indoors and favors transmission of viral illnesses
- Schizophrenia is also about three times more prevalent in people who live in the middle of large cities as compared to those who live in rural areas
- This result suggests transmission of infectious illnesses is facilitated by increased population density
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Defintion: Serious mental disorder characterized by disordered thoughts, delusions (really believe that things are true, whereas it’s obvious for other people that it’s not), hallucinations (mostly auditory but can be visual), and often bizarre behaviors. It has what are known as positive and negative symptoms.
- Schizophrenia is a serious mental disorder that afflicts approximately 1% of world's population
- Its monetary cost to society is enormous (because it’s so prevalent); in the United States this figure exceeds that of the cost of all cancers
- The word literally means “split mind,” but it does not imply a split or multiple personalities