psychotic disorders

Question 1

What is psychosis

Answer 1

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.

Question 2

psychosis -thought processes

Answer 2

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)

Question 3

schizophrenia prevalence

Answer 3

affects 1% of people worldwide

Question 4

Schizophrenia age of onset

Answer 4

Overt symptoms often begin in late adolescence or early adulthood and usually continue throughout life.

Question 5

positive and negative symptoms of schizophrenia

Answer 5

positive: hallucinations and delusions. Negative: thought disorder, language disorder, affective flattening or incongruity

Question 6

Know the diagnostic criteria for schizophrenia

Answer 6

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

Question 7

Genetic inheritance pattern of schizophrenia

Answer 7

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

Question 8

schizophrenia rare copy number variants

Answer 8

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.

Question 9

Schizophrenia SNPs contributing to risk of disease

Answer 9

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

Question 10

Schizophrenia linkage and candidate gene studies

Answer 10

have replicated association to many genes, including key growth factors and regulators of neurodevelopment (including ZNF804A, Neuregulin 1 and 3 and ErbB4).

Question 11

Schizophrenia family-based exome sequencing studies

Answer 11

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.

Question 12

Environmental factors contributing to schizophrenia

Answer 12

viruses, malnutrition before birth, birth complications, and other yet known psychosocial factors.

Question 13

Drugs that can cause psychoses similar to schizophrenia

Answer 13

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)

Question 14

Which neurotransmitters most likely play a role in schizophrenia

Answer 14

dopamine, glutamate and GABA

Question 15

Dopamine theory for schizophrenia

Answer 15

proposes that psychosis is caused by dysregulation of dopamine in the brain. The two pathways affected are the mesolimbic system and the mesocortical system

Question 16

What is the mesolimbic system

Answer 16

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.

Question 17

What role does the mesolimbic system play in schizophrenia

Answer 17

This system regulates reward pathways and emotional processes and hyperactivity of this system is associated with the positive symptoms of schizophrenia.

Question 18

What is the mesocortical system

Answer 18

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.

Question 19

What role does the mesocortical system play in schizophrenia

Answer 19

Hypoactivity of the mesocortical system is associated with the negative symptoms of schizophrenia.

Question 20

Glutamate model of schizophrenia

Answer 20

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.

Question 21

Describe the general neural circuit in schizophrenia

Answer 21

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

Question 22

How does schizophrenia affect the association/ frontal cortex

Answer 22

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.

Question 23

temporal lobe functions

Answer 23

To integrate multimodal sensory information for storage and retrieval of memory, and to attach limbic valence to sensory information.

Question 24

How does schizophrenia affect the temporal lobe

Answer 24

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

Question 25

How is the hippocampus linked with schizophrenia

Answer 25

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

Question 26

How does schizophrenia affect the thalamus

Answer 26

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

Question 27

How does schizophrenia affect the basal ganglia

Answer 27

Caudate nucleus and other basal ganglia nuclei’s volumes are changed.

Question 28

pathology of schizophrenia

Answer 28

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

Question 29

What is the time course for effectiveness of schizophrenia treatments

Answer 29

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.

Question 30

Antipsychotic drugs common side effect and how is it treated

Answer 30

Parkinsonian syndromes- treated with antimuscarinic anticholingergics

Question 31

How do antipsychotics work

Answer 31

compete with dopamine for post-synaptic receptors on many neurons. Five dopamine Receptors (DR1-5) are involved, but DR2 is most sensitive

Question 32

DR2 normal function

Answer 32

Causes neurons to be more sensitive to sensory inputs, compounding patients’ problems with information process and sensory gating, particularly when they are under stress

Question 33

List first generation antipsychotic drugs

Answer 33

Basic types are phenothiazines (chlorpromazine and perphenazine), thioxanthines (thiothixine), and butyrophenones (haloperidol). Chlorpromazine was originally made for antihistamine, but found to have antipsychotic properties.

Question 34

Problems with first generation antipsychotics

Answer 34

Potency was increased, but not efficacy, so dopaminergic side effects like Parkinsonian syndrome and tardive dyskinesia became more problematic

Question 35

What is tardive dyskinesia

Answer 35

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

Question 36

List second generation antipsychotics

Answer 36

aka atypical neuroleptics: Clozapine is most effective, followed by risperidone, olanzapine, quetiapine, asenapine, and ziprasidone

Question 37

Function of second generation antipsychotics

Answer 37

Blocks dopamine, serotonin, norepinephrine, and acetylcholine receptors.

Question 38

Benefits and weaknesses of second generation antipsychotics

Answer 38

benefits: lass parkinsonism. Weakness: causes agranulocytosis (suppression of production of white blood cells)