psychotic disorders Flashcards
What is psychosis
symptom of mental illness indicative of brain malfunction. characterized by derangement of personality and loss of contact with external reality, and may include depression, anxiety, cognitive dysfunction including disturbances in attention, learning, and memory, and delirium.
psychosis -thought processes
They have hallucinations, paranoid delusions (influenced by unseen forces around them), persecutory delusions (believed they are being tormented, harmed, followed, etc), and formal thought disorder (idiosyncratic associations in speech or writing)
schizophrenia prevalence
affects 1% of people worldwide
Schizophrenia age of onset
Overt symptoms often begin in late adolescence or early adulthood and usually continue throughout life.
positive and negative symptoms of schizophrenia
positive: hallucinations and delusions. Negative: thought disorder, language disorder, affective flattening or incongruity
Know the diagnostic criteria for schizophrenia
A. At least 2 characteristic symptoms for at least one month: delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, negative symptoms. B. Social/occupational dysfunction in work, relationships or self care. C. Symptoms for at least 6 months. D. NO mood disorders. E. illness not due to meds. F. illness not due to autism or developmental disorder
Genetic inheritance pattern of schizophrenia
Is a polygenetic disorder, NOT mendelian. Common genetic variations (SNPs) and rare genetic variations (copy number variations and de novo mutations) contribute to risk for the disorder
schizophrenia rare copy number variants
Strong effect- have been reported and replicated at the following chromosomal loci 1q22.1, 2p16.3, 15q11, 16p11.2, 22q11.21. These loci include genes implicated in neuronal development, synapse function and regulation of glutamatergic, GABAergic and dopaminergic neurotransmission.
Schizophrenia SNPs contributing to risk of disease
Includes the major histocompatibility complex (MHC), microRNA, MIR137, targets of miR-137, calcium channel genes (CACNA1C) and the dopamine receptor DRD2. These were discovered through large scale genome wide association studies
Schizophrenia linkage and candidate gene studies
have replicated association to many genes, including key growth factors and regulators of neurodevelopment (including ZNF804A, Neuregulin 1 and 3 and ErbB4).
Schizophrenia family-based exome sequencing studies
have identified an excess of de novo (spontaneous, non-inherited) mutations in patients with schizophrenia. Many of these mutations fall in genes that have a higher expression during early fetal life.
Environmental factors contributing to schizophrenia
viruses, malnutrition before birth, birth complications, and other yet known psychosocial factors.
Drugs that can cause psychoses similar to schizophrenia
Drugs that excite principal neurons or inhibit interneurons: dopamine agonists (stimulants such as cocaine), norepinephrine agonists (stimulants), seretonin agonists (hallucinogens), NMDA antagonism (dissociative anesthetics such as ketamine), acetylcholine antagonists (atropine)
Which neurotransmitters most likely play a role in schizophrenia
dopamine, glutamate and GABA
Dopamine theory for schizophrenia
proposes that psychosis is caused by dysregulation of dopamine in the brain. The two pathways affected are the mesolimbic system and the mesocortical system
What is the mesolimbic system
This system is composed of the dopamine neurons from the ventral tegmental area (VTA) that release dopamine to the nucleus accumbens. This system regulates reward pathways and emotional processes and is associated with the positive symptoms of schizophrenia.
What role does the mesolimbic system play in schizophrenia
This system regulates reward pathways and emotional processes and hyperactivity of this system is associated with the positive symptoms of schizophrenia.
What is the mesocortical system
This system is composed of the dopamine neurons from the VTA and the substantia nigra. The VTA neurons release dopamine to the prefrontal cortex and regulate areas involved in cognitive processing (i.e. the dorsal lateral prefrontal cortex that regulates executive function). The neurons in the substantia nigra release dopamine to the basal ganglia and regulate areas involved with motor control.
What role does the mesocortical system play in schizophrenia
Hypoactivity of the mesocortical system is associated with the negative symptoms of schizophrenia.
Glutamate model of schizophrenia
Proposes that psychosis is caused by hypoactivity of cortical glutamatergic system. Glutamate binds to dopamine neurons and produces hyper and hypoactivity in mesolimbic and mesocortical systems respectively. Prolonged exposure to NMDA antagonists such as PCP produces both positive and negative symptoms of schizophrenia.
Describe the general neural circuit in schizophrenia
Normally, incoming sensory information is processed by the thalamus, which sends the info to the cortical areas, including primary sensory cortex which then sends info to association cortex where a representation of sensory experience is created. In schizophrenia, dysfunction of info processing leads to difficulties in sorting or filtering info from external world
How does schizophrenia affect the association/ frontal cortex
Volume reduction occurs in the association cortex where sulci are widened. Regional cerebral blood flow and glucose metabolism are abnormal in the frontal cortex and hyperactivity of the dorsal lateral prefrontal cortex is an indicatory of insufficiency and deficits in attention, learning and memory.
temporal lobe functions
To integrate multimodal sensory information for storage and retrieval of memory, and to attach limbic valence to sensory information.
How does schizophrenia affect the temporal lobe
mild cortical atrophy of medial temporal lobe and Focal abnormalities indicating abnormal alignment of neurons have been observed in medial temporal lobe structures such as the amygdala, entorhinal cortex, and the hippocampus
How is the hippocampus linked with schizophrenia
nonpyramidal cells in the hippocampus seem to be reduced while pyramidal neurons are not affected. Synaptic organization is changed, altering the plasticity of the hippocampus. Metabolism and blood flow of hippocampus are also increasedat baseline in schizophrenia. Regional cerebral blood flow is also increased duing psychotic symptoms and correlates with positive symptoms
How does schizophrenia affect the thalamus
First, a decrease in the total thalamic volume might signify a breakdown of its sensory filtering capabilities, leading to increased stimulation of primary sensory cortical areas. Second, dysfunction of the medial dorsal nucleus of the thalamus leads to impairments of cortical association areas, especially the dorsal lateral prefrontal cortex
How does schizophrenia affect the basal ganglia
Caudate nucleus and other basal ganglia nuclei’s volumes are changed.
pathology of schizophrenia
deficits in number of inhibitory interneurons and expression of peptides, as well as their migration from the cortical subplate. Reduced synapse numbers in frontal cortex, hippocampus and basal ganglia, and altered dendritic numbers. Enlarged ventricles
What is the time course for effectiveness of schizophrenia treatments
agitation and hallucinations, usually go away within days. Symptoms like delusions usually go away within a few weeks. After about six weeks, many people will see a lot of improvement.
Antipsychotic drugs common side effect and how is it treated
Parkinsonian syndromes- treated with antimuscarinic anticholingergics
How do antipsychotics work
compete with dopamine for post-synaptic receptors on many neurons. Five dopamine Receptors (DR1-5) are involved, but DR2 is most sensitive
DR2 normal function
Causes neurons to be more sensitive to sensory inputs, compounding patients’ problems with information process and sensory gating, particularly when they are under stress
List first generation antipsychotic drugs
Basic types are phenothiazines (chlorpromazine and perphenazine), thioxanthines (thiothixine), and butyrophenones (haloperidol). Chlorpromazine was originally made for antihistamine, but found to have antipsychotic properties.
Problems with first generation antipsychotics
Potency was increased, but not efficacy, so dopaminergic side effects like Parkinsonian syndrome and tardive dyskinesia became more problematic
What is tardive dyskinesia
choreoathetosis that is associated with increased dopamine neurotransmission. After years of chronic blockade by antipsychotics, dopamine receptors on the caudate and putamen (but fortunately not in the cerebral cortex) increase in number, an example of denervation suspersensitivity, and patients develop tardive dyskinesia
List second generation antipsychotics
aka atypical neuroleptics: Clozapine is most effective, followed by risperidone, olanzapine, quetiapine, asenapine, and ziprasidone
Function of second generation antipsychotics
Blocks dopamine, serotonin, norepinephrine, and acetylcholine receptors.
Benefits and weaknesses of second generation antipsychotics
benefits: lass parkinsonism. Weakness: causes agranulocytosis (suppression of production of white blood cells)
