Show Menu

Pathophysiology of Schizophrenia Cheat Sheet by


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")


Lifetime prevalence
1% in US and worldwide
Most commonly in young adults
Equally prevalent in men and women
More frequent in people born in cities and born between January and April and in the northern hemisphere
~ 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
⇨ 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

SZ results from dysreg­ulation of the mesolimbic and mesoco­rtical pathways
Drugs that block dopamine receptors are used in the Tx of SZ
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 cortex5-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

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
Often occur in cycles, altern­ating periods of improv­ement (remissions) with periods of psychosis (relapses)
During acute psychotic episodes, the pt loses touch with reality
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
Delusions (often paranoid)
Halluc­ina­tions (most often auditory)
Thought Disorder (disor­ganized speech, loose associ­ations)
Poverty of speech and speech content
Flattening of emotional responsed
Withdrawal from social contacts
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
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
May not smile or frown in response to happy or sad events
Their voices may not change tone or pitch
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
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
Catatonic pt's will sometimes hold rigid poses for hours and will ignore any external stimuli
May also show stereo­typed, repetitive movements
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


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

Unknown; cause is multif­act­orial
Signif­icant genetic component, with a complex, non-Me­ndelian inheri­tance
The greatest risk factor is a positive family history
Genetic Studies
Many different genes are involved; patients inherit several risk genes
SNPs and CNVs
Pt's more likely to experience premature birth, low birth weight, and perinatal hypoxia
Maternal viral infection during pregnancy (espec­ially during the 2nd trimester)
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

Originates in the substantia nigra ⇨ projects to the striatum
Originates in the hypoth­alamus ⇨ projects to the anterior pituitary
Part of basal ganglia ⇨ involved in the movement and pathog­enesis of Parkin­son's disease
Endocrine function (dopamine inhibits prolactin secretion)
Mesolimbic and Mesoco­ritcal Pathways
Involved in the pathog­enesis of SZ
Both pathways originate in the ventral tegmental area ⇨ project to parts of the limbic system and the cortex
Mesoli­mbic: VTA ⇨ Nucleus accumbens
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



False beliefs that a person holds onto even when they are bizarre or could not possibly be true
May involve fears (paranoid delusions), guilt, jealousy, religion, spirits, one's body and mind control
A perception in the absence of external stimulus (seeing, hearing, or sensing things that are not real)
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)
Thought processes are discon­nected (a sentence or phrase is not logically connected to those that occur before or after; loose associ­ations)
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)

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
Hypera­ctivity of mesolimbic pathway


Very well put together for my level, but need to complete. Treatment recommendation Typical and Atypical psychotropic. Firstline etc

Add a Comment

Your Comment

Please enter your name.

    Please enter your email address

      Please enter your Comment.

          Related Cheat Sheets

          More Cheat Sheets by kfisher17