Questions and Answers
A decrease in the enzyme glutamic acid decarboxylase (GAD) in the cerebral cortex is associated with schizophrenia.
True
NMDA receptors on serotonin neurons are especially vulnerable in schizophrenia.
False
Lysergic acid diethylamide (LSD) acts as an antagonist at 5-HT receptors.
False
An increase in the number of frontal cortex 5-HT2A receptors has been observed in schizophrenia.
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Microglia activation in the brain has been shown in patients with schizophrenia.
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Inflammation's role in schizophrenia has been fully established and widely accepted.
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A proinflammatory state in patients with schizophrenia can influence the dopamine system.
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Parvalbumin-containing interneurons are a type of serotonin neuron involved in schizophrenia.
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The search for neuropathology associated with schizophrenia began with Alzheimer.
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Contemporary neuroscientific concepts and techniques are not used in the study of schizophrenia.
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Johnstone et al. (1976) found significantly smaller ventricles using computerized tomography in patients with schizophrenia.
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Neurodegenerative changes or gliosis are commonly observed in the brains of individuals with schizophrenia.
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Enlarged lateral and third ventricles are a structural brain change found in schizophrenia.
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Structural changes in the brain are currently clinically useful in the diagnosis of individual patients with schizophrenia.
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Structural brain imaging in schizophrenia has shown thicker cortical grey matter.
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Schizophrenia research has disproven the null hypothesis that there are no structural differences in the brain.
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The dopamine hypothesis of schizophrenia asserts that there is an excess of dopamine in schizophrenic patients.
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Increased dopamine in schizophrenia is primarily observed in the ventral striatum.
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Using PET and SPET techniques, scientists observed increased dopamine synthesis in patients with schizophrenia.
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The glutamate hypothesis of schizophrenia emerged after the discovery that NMDA receptor agonists could induce schizophrenia-like psychosis.
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Glutamate is generally considered the more primary abnormality in schizophrenia, with dopamine functioning downstream.
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NMDA-receptor antagonists reduce symptoms of schizophrenia.
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Anti-NMDA receptor antibodies are found only in patients with schizophrenia.
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Gamma-aminobutyric acid (GABA) is identified as the major inhibitory neurotransmitter in the brain and is implicated in schizophrenia.
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Brain atrophy in 17 elderly hospitalized patients with schizophrenia was less than in 8 healthy controls.
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Lateral ventricular enlargement in schizophrenia has been confirmed using MRI and pneumoencephalography.
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According to a meta-analysis of brain volumes in over 18,000 subjects, brain volume in schizophrenia increased by 2.6%.
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The largest effect sizes of structural brain changes in schizophrenia were found in the amygdala, with greater changes in white matter than grey matter.
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There is evidence for an 'organic' subtype in brains with schizophrenia.
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Brain weight in schizophrenia is decreased by 2-3% according to post-mortem neuropathological studies.
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Neurodegenerative processes are confirmed as the primary origin of brain pathology in schizophrenia.
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Techniques such as PET, SPECT, and fMRI have been used to assess patterns of brain activity in schizophrenia.
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Ingvar and Franzen (1974) used injections of radioactive xenon to study cerebral blood flow in chronic, medicated patients with schizophrenia.
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Hypofrontality in schizophrenia was confirmed in a meta-analysis by Hill et al., (2004).
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FMRI studies show that patients with schizophrenia require less frontal cortex activation to achieve the same performance level as controls in working memory tasks.
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Wernicke conceptualized schizophrenia as "psychic splitting," or a failure of integration of mental functions.
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Increased amounts of theta activity and paroxysmal activity are typical findings in the EEG of patients with schizophrenia.
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The P300 response is a visual evoked potential that occurs 300 milliseconds after identifying a target stimulus.
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Alterations in the P50 wave have been linked to the gene coding for a subunit of the nicotinic cholinergic receptor in families with schizophrenia.
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Recent studies focus on brain oscillations and network activity, indicating the coordinated firing of ensembles of neurons between brain areas.
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The Wisconsin Card Sorting Test and N-back task reveal altered prefrontal cortex activity in schizophrenia during working memory tasks.
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Electroencephalography shows decreased synchronization or coherence of electrical activity in the temporal lobes in schizophrenia.
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Study Notes
Schizophrenia
- Schizophrenia is caused by several factors, including a decrease in the synthetic enzyme glutamic acid decarboxylase (GAD) in the cerebral cortex and reductions in connections made by a type of GABA neuron (parvalbumin-containing interneurons).
- Alterations in the expression of GABA receptors and reduced GABA levels as measured by spectroscopy also contribute to the causes of schizophrenia.
- NMDA receptors on GABA neurons may be especially vulnerable.
Serotonin (5-hydroxytryptamine; 5-HT)
- A role for serotonin (5-HT) in schizophrenia has long been considered, and 5-HT₂-receptor antagonism may contribute to the atypical profile of some antipsychotics.
- Alterations in 5-HT receptor densities, including a reduction in the number of frontal cortex 5-HT2A receptors and an increase in 5-HT1A receptors, have been observed.
Inflammatory Markers
- The possible involvement of inflammation in the causation of schizophrenia has been mentioned with regard to risk genes and prenatal factors.
- Studies show alterations in various inflammatory markers in the blood in patients with the disorder, suggestive of a pro-inflammatory state.
- Such activation can influence the dopamine, glutamate, and 5-HT systems.
Neurobiology
- Schizophrenia is at the forefront of attempts to understand psychiatric disorders in terms of alterations in brain structure and function.
- The disorder is associated with alterations in brain structure and function, including changes in the dopamine, glutamate, and GABA systems.
Structural Brain Changes
- Evidence has accrued over the past 40 years that disproves the null hypothesis that there are no structural differences in the brain in schizophrenia.
- The main findings include:
- Decreased brain volume
- Decreased intracranial volume
- Enlarged lateral and third ventricles
- Smaller hippocampus and thalamus
- Thinner cortical grey matter
- Altered white matter pathways
- Neuropathology studies have found:
- Decreased brain weight
- Absence of neurodegenerative changes or gliosis
- Reductions in synaptic and dendritic markers
- Decreased markers of some interneurons
- Smaller pyramidal neurons in some areas
- Fewer thalamic neurons
Dopamine and Schizophrenia
- The dopamine hypothesis of schizophrenia emerged during the 1970s and has persisted.
- Using PET and SPET techniques, scientists found increased dopamine receptors and increased dopamine synthesis in patients with schizophrenia.
- The increase in dopamine is greatest in the striatum and predicts responses to antipsychotic medication.
Glutamate and Schizophrenia
- The glutamate hypothesis of schizophrenia emerged after a key finding: antagonists of the NMDA type of glutamate receptor can induce schizophrenia-like psychosis.
- The NMDA receptor hypofunction model suggests a developmental abnormality in the receptor.
- Glutamate and dopamine systems are intricately linked, and their dysfunction in schizophrenia is thought to reflect shared factors.
GABA and Schizophrenia
- Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, and its function is implicated in schizophrenia.
- Evidence for glutamate involvement in schizophrenia includes:
- NMDA-receptor antagonists exacerbate schizophrenia symptoms.
- NMDA-receptor co-agonists reduce some symptoms.
- Glutamate markers and receptors are altered in the brains of people with schizophrenia.
- Altered levels of glutamate and its metabolites have been shown using spectroscopy in people with schizophrenia.
- Schizophrenia risk genes affect glutamate signaling.
- Anti-NMDA receptor antibodies are found in some cases of schizophrenia.
Brain Atrophy in Schizophrenia
- Brain atrophy in schizophrenia was greater than in healthy controls, with a ~30% increase in ventricular volumes and a 2.6% decrease in brain volume.
- The structural brain changes occur early in childhood and affect the hippocampus and thalamus, with greater changes in grey matter than white matter.
- Longitudinal studies have attempted to identify the course of structural brain changes, with some volume reductions observed before the onset of symptoms and further loss of grey and white matter thereafter.
Neuropathology
- Post-mortem neuropathological studies have sought to explain the cellular and molecular basis for neuroimaging findings.
- Brain weight is decreased by 2-3%, with no evidence of neurodegenerative processes, supporting a neurodevelopmental origin of the pathology.
- Reductions are found in some markers of synapses and dendrites, and in specific neuronal populations.
Functional Brain Imaging
- Techniques such as PET, SPECT, and fMRI have been used to assess patterns of brain activity in schizophrenia.
- Study designs usually compare groups of patients with controls, either at rest or during activity.
Cognitive Deficits
- Cerebral blood flow studies have found decreased perfusion of the frontal cortex compared with the posterior regions in chronic, medicated patients with schizophrenia.
- Altered frontal activity is also apparent in fMRI studies, particularly in the prefrontal cortex during performance of working memory tasks.
- The profile of changes is complex, with patients requiring more frontal cortex activation to achieve the same level of performance as controls, suggesting reduced "efficiency" of cortical processing.
Aberrant Connectivity
- The "dysconnectivity" model suggests that the activity of different brain circuits or networks is aberrant in schizophrenia.
- Some variants of this model also involve a structural component, consistent with the structural imaging and neuropathology findings mentioned earlier.
Neurophysiological Findings
- Neurophysiological function in schizophrenia has been examined using a range of methods, including electroencephalography (EEG), sensory evoked potentials (P300 and P50), and magnetoencephalography (MEG).
- Abnormalities in these measures have been observed in patients with schizophrenia and their relatives, suggesting that they may be useful as biomarkers for the disorder.
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Description
This quiz covers the neurological causes of schizophrenia, including the role of GABA, glutamic acid decarboxylase, and NMDA receptors in the development of the disorder.
