Disorders (Schizophrenia) Flashcards
Schizophrenia
> . A group of psychotic disorders characterized by:
. Abnormal thoughts, moods, and actions
. A distorted sense of reality
. Thoughts that do not logically fit together
. Psychotic: a loss of contact with reality
Originally thought to be caused by bad parenting!
Stages of Schizophrenia
Stage 0. Premorbid stage, Risk factors develop, including genetic, social, and behavioural factors
Stage 1. Prodrome phase, Risk factors emerge at clinically detectable levels
Stage 2. At least one full psychotic episode occurs
Stage 3. Inter-episode deficits emerge with psychosis
Stage 4. Substantial deterioration, with treatments at best being symptomatic and rehabilitative
Genetic applicability of Schizophrenia
> . Susceptibility genes and psycho-social stressors combine, stressors exceed a vulnerability threshold to produce symptoms of psychosis.
- The stress-vulnerability model is the accepted approach as it explains neurodevelopment factors
- Onset of schizophrenia-like symptoms are more likely in late adolescence or early adulthood
- Statistically, men have an earlier onset than women (by 5-7 years), who may be protected by estrogens levels
- Predictors of recovery include being female, rapid (vs. insidious) onset of symptoms, older age of first episode, predominantly positive symptoms, presence of mood symptoms, and good pre-illness functioning.
Categorization of Schizophrenia
§ Criterion A lists the five key symptoms of schizophrenia:
1) delusions, 2) hallucinations, 3) disorganized speech, 4) disorganized or catatonic behaviour, and 5) negative symptoms.
§ 2 of these 5 symptoms are required AND at least one symptom must be one of the first three (delusions, hallucinations, disorganized speech).
Positive symptoms – Schizophrenia
> . “Excesses” indicating overt psychosis,
. occurrences beyond normal experience:
. Delusions: deviance in the content of thought: delusions of persecution, grandeur, outside control
- Thought insertion, broadcast, and withdrawal
. Hallucinations: distortions of perception, mostly auditory
- Audible thoughts, voices arguing, voices commenting
. Incoherence: disorganized speech, inability to organize ideas and speech. Also loose associations / derailment
Negative symptoms of Schizophrenia
> . Behavioural deficits (diminished experience)
. Avolition: apathy, a complete lack of interest in everyday activities, e.g., hygiene, work
. Loss of affect: no stimulus can elicit an emotional response. Motor (outward) vs. affect (inner)
. Anhedonia: the inability to experience pleasure
. Also Catatonia: postures are adopted and held for long periods of time: including waxy flexibility
•The stress-vulnerability model is the accepted approach as it explains neurodevelopment factors, and is supported by a strong hereditability coefficient, estimated to be 50% across monozygotic twins.
•A study examining a large sample of adolescents at-risk found that cortisol levels, an index of stress, were significantly elevated among those who transitioned to psychosis (Walker et al., 2013).
•A stressful or traumatic incident can sometimes trigger the symptoms of schizophrenia in particularly vulnerable people.
The Dopamine Hypothesis; Part 1
> . Schizophrenia is caused by dysfunctional dopaminergic neurons in the mesolimbic (positive symptoms) and mesocortical (negative) pathways.
. “Meso”: prefix (Greek) meaning ‘in the middle‘
. 1950s: phenothiazines are shown to control positive symptoms
. Phenothiazines block the functioning of dopamine D2 receptors, reducing overstimulation
. Additionally, amphetamine, which induces positive symptoms, stimulates dopamine release
. 1960’s found that Parkinson’s patients had reduced dopamine in striatum (part of basal ganglia)
The Dopamine Hypothesis: Part 2
–Disruption of dopaminergic transmission might cause Parkinsonism.
–Parkinson-like side effects of Thorazine and Reserpine…
•A hypothesis is born:
–Actions of Thorazine and Reserpine better understood
–Amphetamine-induced and cocaine-induced psychosis
>. Schizophrenia is associated with an excess of dopamine in the limbic system and the frontal lobes
>. Studies show that schizophrenia can be reduced by:
The Dopamine Hypothesis: Part 3
- The blocking of D2 receptors: the better the block the greater the reduction in schizophrenic symptoms
- Drugs (e.g., Resperine) that prevent the storage of monoamines (i.e., dopamine) in synaptic vesicles
- Drugs that block the synthesis of dopamine
- Drugs that stimulate dopamine autoreceptors on the presynaptic membrane
Further evidence comes from drugs that induce schizophrenia and act as dopamine agonists:
>. Amphetamine
>. Cocaine
>. L-Dopa
>. Dopamine antagonists can relieve the symptoms induced by the above drugs
>. L-Dopa is administered to patients suffering Parkinson’s disease. When given in large amounts it can induce the symptoms of schizophrenia
The Glutamate Hypothesis: Part 1
- Glutamate is one of the excitatory neurotransmitters and the most abundant neurotransmitter in the brain.
- Glutamate is mediated by N-methyl-D-aspartate receptors (NMDARs)
- Patients with schizophrenia had decreased glutamate levels.
- Patients who abuse NMDAR antagonists, such as phencyclidine (PCP) or ketamine, frequently show psychotic symptoms.
- Furthermore, cortical atrophy correlates with negative and cognitive symptoms in chronic schizophrenia but not with the severity of psychosis.
The Glutamate Hypothesis: Part 2
> . 1980’s: Drugs such as Clozaril were found to be more effective at treating both +/- symptoms of schizophrenia
. Clozaril, an atypical antipsychotic, inhibits D2 less than 1st generation antipsychotics and also affects other neurotransmitters, and has less side effects.
. This indicated other neurotransmitters were involved
. Additionally, a lack of a “smoking gun” that would cause excessive dopamine was never found.
. PCP (phencyclidine) and ketamine (anesthetic) were known to induce both +/- symptoms of schizophrenia
The Glutamate Hypothesis: Part 3
> . These drugs are now thought to mimic the key molecular changes in the brains of schizophrenics
. These drugs impair the functioning of neurons that rely on glutamate (most common excitatory neurotransmitter)
. Specifically, they block a type of glutamate receptor known as the NMDA (N-methyl-D-aspartate) receptor
. NMDA participates in brain development, learning, memory, and neural processing in general
. It also plays a crucial role in regulating dopamine
. Blockage of NMDA receptors produces the same disturbances characteristic of positive schizophrenia
The Glutamate Hypothesis: Part 4
> . Additionally, Clozaril can reverse the effects of PCP
. The smoking gun: Fewer NMDA receptors Abnormal glutamate release
. Predisposition: if one twin has schizophrenia then the other has a 50% chance of also being inflicted
Serotonin
> . The serotonin (5-hydroxytryptamine; 5-HT) hypothesis of schizophrenia is based on the early studies of interactions between the hallucinogenic drug lysergic acid diethylamide (LSD) and 5-HT.
. Serotonin antagonists improve the extrapyramidal effects of antipsychotics. However, direct evidence of serotonergic dysfunction in the pathogenesis of schizophrenia is not yet available.
. Maybe related to 5-HT receptor hyperfunction (stress-induced serotonergic overdrive) in the cerebral cortex
EEG Findings
Schizophrenics have higher early-ERP components than controls
>. Such a condition is known as sensory overload
>. But they have lower later-ERP components
>. This suggests they have attentional deficits
>. ERPs are consistent with the idea that schizophrenics may overloaded with masses of sensory information but have trouble extracting meaningful information from them
>. Evidence also comes from the spontaneous EEG
>. Schizophrenics undertaking perceptual experiments exhibit a deficit of gamma band activity in the brain
>. Gamma indexes the level of ‘binding’ in the brain
>. Thus neural networks in the brain are not integration
>. There is a relationship between symptom intensity and lack of neural synchronization.
