Psychosis
A symptom of mental illness characterized by the loss of contact with reality |
Manifestations: hallucinations, disorganized thoughts and speech, emotions exhibited in an abnormal manner |
Causes of psychosis
• Functional: schizophrenia, manic phase of bipolar disorder, psychotic depression
• Organic: Alzheimer's disease and other causes of dementia, brain tumors
• Drug abuse: cocaine, amphetamine, PCP ("angel dust")
Epidemiology
Lifetime prevalence |
1% in US and worldwide |
Onset |
Most commonly in young adults |
Sex |
Equally prevalent in men and women |
Frequency |
More frequent in people born in cities and born between January and April and in the northern hemisphere |
Suicide |
~ 15% |
Structural Abnormalities
Decreased cortical thickness in the absence of gliosis |
⇨ Gliosis (proliferation of the glial cells) occurs as a compensatory change in the degenerative disease in the brain (typically happens later in life) |
Reduction in volume of the frontal lobe, medial temporal lobe, thalamic and hippocampus |
⇨ increased ventricular size |
Decreased blood flow and glucose metabolism in the frontal lobe and left temporal lobe |
Abnormal (excessive) synaptic pruning |
⇨ decreased number of glutamanergic dendritic spines in PFC in individuals with schizophrenia |
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⇨ Synaptic Pruning: the process of synapse elimination that occurs between age 2 and onset of puberty |
Multiple NT systems interact in a particular way to cause the signs and Sx of SZ |
Functional abnormalities are related to alterations in: |
Dopamine, Glutamate, Serotonin |
New Research: a person's risk of schizophrenia is increased if they inherit specific variants in a gene related to synaptic pruning
⇨ Complement Component 4 (C4): plays a role in the immune system, as well as brain development
Pathogenesis of SZ | DOPAMINE
Hypothesis |
SZ results from dysregulation of the mesolimbic and mesocortical pathways |
Reasons |
Drugs that block dopamine receptors are used in the Tx of SZ |
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Drugs that increase dopaminergic activity (ie. amphetamines) can cause psychosis |
Pathogenesis of SZ | SEROTONIN
▶ Serotonergic neurons originate in the raphe nuclei and project extensively to all regions of the cortex, basal ganglia, limbic system, hypothalamus, cerebellum and brain stem |
▶ High density of 5-HT-2A receptors in the cerebral cortex ⇨ 5-HT-2A Receptors modulate the release of DA, glutamate, NE, GABA, and ACh ⇨ regulation of cognitive processes, working memory, and attention |
Serotonin 5-HT-2A receptor blockers (2nd generation antipsychotic agents) are used in the Tx of SZ |
Clinical Manifestations
Definition |
a chronic disorder of thought and affect with the individual having a significant disturbance in interpersonal relationships and ability to function in society on a daily basis |
Symptomology |
Often occur in cycles, alternating periods of improvement (remissions) with periods of psychosis (relapses) |
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During acute psychotic episodes, the pt loses touch with reality |
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Impaired psychosocial functioning during remissions |
Although the course of illness is variable, the long-term prognosis is poor |
Grouped into positive, negative, and cognitive symptoms |
Positive |
Delusions (often paranoid) |
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Hallucinations (most often auditory) |
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Thought Disorder (disorganized speech, loose associations) |
Negative |
Poverty of speech and speech content |
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Flattening of emotional responsed |
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Withdrawal from social contacts |
Cognitive |
Impaired attention, working memory, and executive function |
Positive sx correlate with abnormalities in limbic pathways in the brain
⇨ Hyperactivity of Mesolimbic DA pathways ⇨ positive sx
Negative and cognitive sx can be associated with prefrontal lobe dysfunction
⇨ hypoactivity of mesocortical DA pathway ⇨ negative and cognitive sx
Positive sx typically respond to tx, while negative and cognitive sx often persist and contribute to chronic disability
Negative Symptoms
Alogia & Poverty of Speech |
May speak very little or speech may have little meaningful content |
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May have long delays between words and sentences, as if the connections between thoughts and speech were interrupted or blocked |
Flattening or blunting of affect |
May have reduced emotional expression |
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May not smile or frown in response to happy or sad events |
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Their voices may not change tone or pitch |
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May not maintain eye contact or other kinds of emotional links with other people |
Anhedonia and Avolition |
May seem to lose interest in and energy for pleasurable activities and achievements |
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Avolition = lack of desire, drive, or motivation to pursue meaningful goals |
Catatonia and Posturing |
May seem to freeze into unusual body positions or stop moving entirely |
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Catatonic pt's will sometimes hold rigid poses for hours and will ignore any external stimuli |
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May also show stereotyped, repetitive movements |
COGNITIVE SYMPTOMS |
Lack of Motivation and Social Withdrawal |
Contribute to poor-self care skills, difficulties maintaining employment, and living independently |
Impaired Attention |
Trouble focusing or paying attention |
Impaired Working Memory |
Ability to use information immediately after learning it |
Poor executive function |
Ability to understand information and use it to make decisions |
➩ Patients often have difficulty learning from their experiences and they can repeatedly make the same mistakes in situations requiring judgment
➩ Poor insight into the severity of their disorder ➩ they tend to stop therapy
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Schizophrenia
A chronic psychiatric disorder characterized by impairments in the perception of realist, most commonly manifesting as disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affact, in the context of significant social or occupational dysfunction |
Multiple emotional and cognitive functions are affects --> results in disability for a large proportion of SZ patients |
Only partially effective, symptomatic treatment are available |
• Nothing CURES/FIXES the problem
Etiology and Causes
Etiology |
Unknown; cause is multifactorial |
Genetics |
Significant genetic component, with a complex, non-Mendelian inheritance |
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The greatest risk factor is a positive family history |
Genetic Studies |
Many different genes are involved; patients inherit several risk genes |
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SNPs and CNVs |
Environment |
Pt's more likely to experience premature birth, low birth weight, and perinatal hypoxia |
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Maternal viral infection during pregnancy (especially during the 2nd trimester) |
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Early neurodevelopmental defect (brain vulnerability determines by genetic predisposition) combined with environmental factors/stressors ⇨ abnormal migration of neurons during CNS development ⇨ results in abnormal neuronal connectivity and abnormal brain circuits --> SZ |
Dopaminergic Pathways in the Brain
Nigrostriatal |
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Originates in the substantia nigra ⇨ projects to the striatum |
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Originates in the hypothalamus ⇨ projects to the anterior pituitary |
Tuberoinfundibular |
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Part of basal ganglia ⇨ involved in the movement and pathogenesis of Parkinson's disease |
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Endocrine function (dopamine inhibits prolactin secretion) |
Mesolimbic and Mesocoritcal Pathways |
Involved in the pathogenesis of SZ |
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Both pathways originate in the ventral tegmental area ⇨ project to parts of the limbic system and the cortex |
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Mesolimbic: VTA ⇨ Nucleus accumbens |
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Mesocortical: VTA ⇨ Prefrontal Cortex (PFC) |
Pathogenesis of SZ | GLUTAMATE
The glutamatergic system is most widespread excitatory NT system in the brain |
Unlike dopaminergic neurons, glutamatergic neurons are distributed throughout the brain and play a role in sensory processing, memory, and other higher-level functions |
Abnormal synaptic pruning of glutaminergic neurons ⇨ Decreased number of glutametergic dendritic spines in individuals with SZ ⇨ abnormal (decreased) neuronal connectivity |
Glutamate Receptors: ionotropic (NMDA, AMPA, KA) and metabotropic glutamate receptors |
▶ Normally, glutamatergic neurons inhibit dopaminergic neuronal activity in the VTA |
▶ Glutamatergic neurons do NOT interact with dopaminergic neurons directly, but indirectly through GABA (inhibitory) interneurons |
▶ When glutamatergic neuron is activated in the PFC ⇨ GABA neuron activation in the VTA ⇨ inhibition of dopamine neuron activity in the VTA |
In SZ: NMDA receptor hypofunction hypothesis ⇨ glutamatergic neuronal or NMDA receptor deficiency results in dopaminergic hyperactivity ⇨ hallucinations and delusions ⇨ hyperactivity of mesolimbic pathway |
The most important glutamate receptor is NMDA ⇨ it carries the MOST excitatory neurotransmission in the brain
▶ = NORMAL FUNCTIONS
**POSITIVE SYMPTOMS
Delusions |
False beliefs that a person holds onto even when they are bizarre or could not possibly be true |
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May involve fears (paranoid delusions), guilt, jealousy, religion, spirits, one's body and mind control |
Hallucinations |
A perception in the absence of external stimulus (seeing, hearing, or sensing things that are not real) |
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Most common are auditory hallucinations (hearing voices); voices may keep a running commentary on the person's behaviors, tell them what to do, carry on conversations about them, accuse them, or may have arguments with each other |
Other Hallucinations |
Visual, tactile, olfactory, gustatory |
Disorganized speech, thoughts, and beliefs |
May lose track of their ideas, meanings, and words (Word Salad) |
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Thought processes are disconnected (a sentence or phrase is not logically connected to those that occur before or after; loose associations) |
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Ideas and images may become jumbled or linked together illogically or words and meaning that should be linked instead may become disconnected |
Disorganized Movement and Behaviors |
May use exaggerated or repeated gestures, or may seem to be fidgeting, hyperactive, or preoccupied with meaningless physical movements |
Hypothesis of SZ (Together)
Dopamine |
SZ comes from dysregulation of mesolimbic and mesocortical pathways |
NMDA Receptor Hypofunction Hypothesis |
Glutamatergic neuronal or NMDA receptor deficiency results in dopaminergic hyperactivity, which leads to hallucinations and delusions |
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Hyperactivity of mesolimbic pathway |
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Comments
Very well put together for my level, but need to complete. Treatment recommendation Typical and Atypical psychotropic. Firstline etc
this is amazing! love the pathogensis sections!
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