Schizophrenia Flashcards
Psychiatric disorders
Disorders of psychological function sufficiently severe(ernstig genoeg) to require treatment
DSM-5
Diagnostic and Statistical Manual of the American Psychiatric Association
2 main difficulties in diagnosing particular psychiatric disorders
- Patients suffering from the same disorder often display different symptoms, and
- Patients suffering from different disorders often display many of the same symptoms.
Schizophrenia means…
the splitting of psychic functions
Waxy flexibility
Reacting like a mannequin, not resisting movement and holding new position until being moved again.
Schizophrenia with catatonia
Schizophrenia characterized by long periods of immobility and waxy flexibility
Echolalia
Vocalized repetition of some or all of what has just been heard
Positive symptoms
Symptoms that seem to represent an excess of typical function
Negative symptoms
Symptoms that seem to represent a reduction or loss of typical function
Examples of positive symptoms
- Delusions. Delusions of being controlled (e.g., “Martians are making me steal”), delusions of persecution (e.g., “My mother is poisoning me”), or delusions of grandeur (e.g., “Steph Curry admires my jump shot”).
- Hallucinations. Imaginary voices making critical comments or telling patients what to do.
- Inappropriate affect. Failure to react with the appropriate emotion to positive or negative events.
- Disorganized speech or thought. Illogical thinking, peculiar associations among ideas, belief in supernatural forces.
- Odd behavior. Difficulty performing everyday tasks, lack of personal hygiene, talking in rhymes.
Examples of negative symptoms
- Affective flattening –> Diminished emotional expression.
- Avolition –> Reduction or absence of motivation.
- Catatonia –> Remaining motionless, often in awkward positions for long periods.
Series of studies that established schizophrenia’s genetic basis
- Although only 1 percent of the population develops schizophrenia, the probability of schizophrenia occurring in a close biological relative (i.e., a parent, child, or sibling) of a patient with schizophrenia is about 10 percent, even if the patient with schizophrenia was adopted shortly after birth by a healthy family.
- The concordance rates for schizophrenia are higher in monozygotic twins (45–50 percent) than in dizygotic twins (10–17 percent).
- Adoption studies found that the risk of schizophrenia is increased by the presence of the disorder in biological parents but not by its presence in adoptive parents.
Variety of early experiential factors have been implicated in the development of schizophrenia
- Birth complications, maternal stress, prenatal infections, socioeconomic factors, urban birth or residing in an urban setting, and childhood adversity.
- Such early experiences are thought to alter the typical course of neurodevelopment leading to schizophrenia in individuals who have a genetic susceptibility, presumably through epigenetic mechanisms.
Supporting neurodevelopmental theory of schizophrenia are:
- The fact that schizophrenia and autism spectrum disorders share many of the same causal factors (e.g., genetic risk factors, environmental triggers)
- The study of two 20th-century famines(hongersnoden): Fetuses whose pregnant mothers suffered in those famines were more likely to develop schizophrenia as adults.
Antipsychotic drug
A drug that is meant to treat certain symptoms of schizophrenia and bipolar disorders.
Chlorpromazine
- Was developed by a French drug company as an antihistamine.
- In 1950, a surgeon noticed that chlorpromazine given prior to surgery to counteract swelling had calming effect on some of his patients, and he suggested that it might have a calming effect on difficult to handle patients with psychosis.
- Discovery that chlorpromazine alleviates the symptoms of schizophrenia: Agitated patients with schizophrenia were calmed by chlorpromazine, and emotionally blunted patients with schizophrenia were activated by it.
- Chlorpromazine does not cure schizophrenia, but often reduces the severity of symptoms enough to allow institutionalized patients to be discharged.
Psychosis
A loss of touch with reality
Reserpine
- The active ingredient of the snakeroot plant which had long been used in India for the treatment of mental illness.
- Gave reserpine to his patients with schizophrenia and confirmed its antipsychotic action.
- No longer used in the treatment of schizophrenia because it produces a dangerous decline in blood pressure at the doses needed for successful treatment.
Chemical structures of chlorpromazine and reserpine dissimilar, but antipsychotic effects similar in 2 major respects.
- Antipsychotic effect of both drugs is manifested only after a patient has been medicated for 2 or 3 weeks.
- The onset of this antipsychotic effect is usually associated with motor effects similar to the symptoms of Parkinson’s disease (e.g., muscular rigidity, a general decrease in voluntary movement). These similarities suggested to researchers that chlorpromazine and reserpine were acting through the same mechanism—one that was related to Parkinson’s disease.
Dopamine theory of schizophrenia
The theory that schizophrenia is caused by too much dopamine and, conversely, that antipsychotic drugs exert their effects by decreasing dopamine levels.
Lending instant support to the dopamine theory of
schizophrenia were two already well established facts.
- The antipsychotic drug reserpine was known to deplete the brain of dopamine and other monoamines by breaking down the synaptic vesicles in which these neurotransmitters are stored.
- Drugs such as amphetamine and cocaine, which can trigger episodes that resemble schizophrenia in healthy users, were known to increase the extracellular levels of dopamine and other monoamines in the brain.
The major difficulty in studying and treating schizophrenia is accurately defining it …
- Its symptoms are complex and diverse;
- Symptoms overlap greatly with those of other psychiatric disorders
- Symptoms frequently change during the progression of the disorder.
- Various neurological disorders (e.g., complex partial epilepsy; see Chapter 10) have symptoms that might suggest a diagnosis of schizophrenia.
Schizophrenia spectrum disorders
Because the current definition of schizophrenia overlaps with that of several different disorders, the DSM5 prefers to use the label schizophrenia spectrum disorders to refer to schizophrenia and related disorders.
Metabolites
Substances that are created by the breakdown of another substance in cells
Chlorpromazine and reserpine antagonize transmission at dopamine synapses but they do it in different ways:
Reserpine by depleting(verminderen) the brain of dopamine and chlorpromazine by binding to dopamine receptors.
Receptor blocker (at dopamine synapses)
It binds to dopamine receptors without activating them and, in so doing, keeps dopamine from activating them
Haloperidol
One of the most potent anti psychotic drugs of its day, it had a relatively low affinity for dopamine receptors.
Phenotiazines
All bind effectively to both D1 and D2 receptors
Butyrophenones
All bind effectively to D2 receptors but not to D1 receptors.
Typical antipsychotics (the first generation of antipsychotic drugs)
The degree to which typical antipsychotics bind to D2 receptors is highly correlated with their effectiveness in suppressing the symptoms of schizophrenia.
Spiroperidol( is a butyrophenone)
Had the greatest affinity for D2 receptors and the most potent antipsychotic effect
D2 version of the dopamine theory of schizophrenia could not explain two general findings:
- Although typical antipsychotics block activity at D2 receptors within hours, their therapeutic effects are usually not apparent for several weeks.
- Most antipsychotics are only effective in the treatment of schizophrenia’s positive symptoms, but not its negative symptoms.
Current version of the dopamine theory
Excessive activity at D2 receptors is one factor in the disorder but there are many other factors as well.
Atypical antipsychotics(also known as second generation antipsychotics)
Drugs that are effective against schizophrenia but yet do not bind strongly to D2 receptors
Clozapine
The first atypical anti psychotic to be approved for clinical use, has an affinity for D1 receptors, D4 receptors, and several serotonin and histamine receptors, but only a slight affinity for D2 receptors
Diagnosis of schizophrenia
The frequent recurrence of any two of the symptoms for 1 month is currently sufficient for the diagnosis of schizophrenia—provided that one of the symptoms is delusions, hallucinations, or disorganized speech.
3 important things to be aware of in atypical antipsychotics
- Some D2 receptor antagonists have no antipsychotic actions
- Drugs that enhance the effects of glycine or block the effects of glutamate are proving to be effective treatments for schizophrenia in preliminary tests;
- There is growing appreciation of the role of glutamatergic dysregulation in the development of schizophrenia
Psychedelic drugs
- Drugs whose primary action is to alter perception, emotion, and cognition.
- Classical hallucinogens –> LSD, psilocybin, and mescaline
- Dissociative hallucinogens –> ketamine and phencyclidine
- Cannabinoids
Researchers have pursued two lines of research on
psychedelics..
- Focused on those psychedelic drugs that produce effects similar to the symptoms of psychiatric disorders (e.g., illusions, hallucinations, paranoia, panic), and they used the drugs to model the disorders.
- Focused on the feelings of boundlessness, unity, and bliss(geluk) reported by some users and attempted to use psychedelics in the treatment of psychiatric disorders.
1990s renewal of interest in utilizing psychedelic drugs to study the mechanisms of schizophrenia and other psychiatric disorders. What stimulated this?
- The development of techniques for imaging the effects of drugs in the human brain
- Increased understanding of the mechanisms of psychedelic drug action
1990s renewal of interest in utilizing psychedelic drugs led to two important conclusions
- The effects of classical hallucinogens, such as LSD, mimic the positive symptoms of schizophrenia (e.g., hallucinations and disorganized thought) by acting as agonists of particular serotonin receptors;
- Dissociative hallucinogens (e.g., ketamine) mimic the negative symptoms of schizophrenia by acting as antagonists of glutamate receptors
Study of schizophrenia related genes and their effects pointed to several processes that could play important roles in development of the disorder
Schizophrenia related genes have been shown to:
- disrupt neural proliferation(vermenigvuldiging) and migration
- pruning(vermindering) synaptic during neurodevelopment
- Myelination or transmission at glutamatergic and GABAergic synapses
One important general point about schizophrenia related genes has recently emerged.
Some genes that increase a person’s susceptibility to schizophrenia have also been linked to other psychiatric and neurological disorders.
Many studies have assessed brain development in patients with, or at risk for, schizophrenia. Four important findings have emerged from various meta-analyses of those studies
- Individuals who have not been diagnosed with schizophrenia but are at risk for the disorder (e.g., because they have close relatives with schizophrenia) display volume reductions in some parts of the brain.
- Extensive brain changes already exist when patients first seek medical treatment and receive their first brain scans.
- Subsequent brain scans reveal that the brain changes continue to develop after the initial diagnosis.
- Alterations to different areas of the brain develop at different rates
Where do schizophrenia related volume reductions develop and what are the results?
- Hippocampus, amygdala, thalamus, and nucleus accumbens were found to be significantly smaller in those with schizophrenia.
- In both gray and white matter, and they are most consistently observed in the temporal lobes
- -> Reduced neuron size and reduced dendritic and axonal arborization
