Latest NU 606 Final Exam Study Guide:
Pathophysiology of Psych & GI Disorders
,NU 606 Final Exam Study Guide Schizophrenia & Psych Disorders
Neurotransmitter in Schizophrenia: Dopamine dysfunction is most commonly implicated.
- Excessive dopamine activity in the mesolimbic pathway of the brain is linked with the positive
symptoms of schizophrenia like hallucinations and delusions
- Reduced dopamine activity in the prefrontal cortex of the brain is linked with the negative symptoms of
schizophrenia like lack of motivation and emotional flatness
- Glutamate
o Hypofunction: dysfunction in the glutamate system, particularly the NDMA receptor is a key
factor in schizophrenia
o Link to dopamine: some research suggests that glutamate dysfunction may lead to the
hyperactivity of the dopamine system
o Symptoms: glutamate abnormalities are linked negative symptoms and cognitive impairment
Brain Region in Schizophrenia: Prefrontal cortex shows major structural abnormalities.
- Reduced gray matter volume: there is a consistent finding of lower gray matter volume in specific brain
regions, which is associated with cognitive and perceptual deficits
- Prefrontal cortex: reduced volume here is linked to difficulties with executive function like decision-
making and working memory
- Cortical thinning and reduced surface area: both cortical thinning and a reduction in overall surface area
are found across the prefrontal cortex
- Disrupted white matter: there is evidence of reduced white matter integrity, including abnormalities in
key tracts like the corpus callosum, which connects the left and right prefrontal cortices
- Neural circuit: these structural changes, especially the loss of synaptic connections (spines and
dendrites) lead to altered neural circuits. This disruption affects the connections between neurons,
leading to loss of the persistent firing needed for strong mental representations.
, - Consequences of these abnormalities: o Cognitive deficits: these structural change are linked to the
cognitive and executive function impairments seen in schizophrenia, such as deficits in working
memory, attention, and problemsolving
o Impaired function: the structural damage results in functional deficits, such as reduced metabolic
activity and blood flow in the prefrontal cortex
o Progression: the structural changes are not static and can be progressive, with some evidence
suggesting they may worsen over time, particularly in the period just before and after the onset
of the disorder
Dopamine Hypothesis: Increased dopamine activity in the mesolimbic pathway → positive symptoms.
- The dopamine hypothesis of schizophrenia suggests that excess dopamine activity in certain regions
cause positive symptoms (hallucinations and delusions), while low dopamine activity in other areas may
be responsible for negative and cognitive symptoms (lack of motivation and memory problems). This
theory is supported by evidence such as antipsychotic drugs blocking dopamine D2 receptors and drugs
that increase dopamine, like amphetamines trigger psychotic symptoms
Glutamate Dysfunction in Schizophrenia: Reduced NMDA receptor function is a hallmark.
- Hypofunction of glutamate: dysfunction in the glutamate system, particularly the NDMA receptor is a
key factor in schizophrenia
- NMDA receptor hypofunction: a central hypothesis is that reduced function of NMDA receptors,
particularly on GABA interneurons, leads to impaired inhibitory control. This can result in
overstimulation of dopamine pathways, contributing to positive symptoms of psychosis.
- Altered glutamate/glutamine cycling: dysfunction glutamate-glutamine cycling, possibly due to
astrocytic problems, could lead to imbalances in glutamate and glutamine levels impact synaptic activity
- Excitotoxicity: in chronic schizophrenia, elevated glutamate levels could lead to excitotoxic effects,
causing a degeneration of glutamatergic neurons over time, which would be reflected in lower glutamate
measures
Pathophysiology of Psych & GI Disorders
,NU 606 Final Exam Study Guide Schizophrenia & Psych Disorders
Neurotransmitter in Schizophrenia: Dopamine dysfunction is most commonly implicated.
- Excessive dopamine activity in the mesolimbic pathway of the brain is linked with the positive
symptoms of schizophrenia like hallucinations and delusions
- Reduced dopamine activity in the prefrontal cortex of the brain is linked with the negative symptoms of
schizophrenia like lack of motivation and emotional flatness
- Glutamate
o Hypofunction: dysfunction in the glutamate system, particularly the NDMA receptor is a key
factor in schizophrenia
o Link to dopamine: some research suggests that glutamate dysfunction may lead to the
hyperactivity of the dopamine system
o Symptoms: glutamate abnormalities are linked negative symptoms and cognitive impairment
Brain Region in Schizophrenia: Prefrontal cortex shows major structural abnormalities.
- Reduced gray matter volume: there is a consistent finding of lower gray matter volume in specific brain
regions, which is associated with cognitive and perceptual deficits
- Prefrontal cortex: reduced volume here is linked to difficulties with executive function like decision-
making and working memory
- Cortical thinning and reduced surface area: both cortical thinning and a reduction in overall surface area
are found across the prefrontal cortex
- Disrupted white matter: there is evidence of reduced white matter integrity, including abnormalities in
key tracts like the corpus callosum, which connects the left and right prefrontal cortices
- Neural circuit: these structural changes, especially the loss of synaptic connections (spines and
dendrites) lead to altered neural circuits. This disruption affects the connections between neurons,
leading to loss of the persistent firing needed for strong mental representations.
, - Consequences of these abnormalities: o Cognitive deficits: these structural change are linked to the
cognitive and executive function impairments seen in schizophrenia, such as deficits in working
memory, attention, and problemsolving
o Impaired function: the structural damage results in functional deficits, such as reduced metabolic
activity and blood flow in the prefrontal cortex
o Progression: the structural changes are not static and can be progressive, with some evidence
suggesting they may worsen over time, particularly in the period just before and after the onset
of the disorder
Dopamine Hypothesis: Increased dopamine activity in the mesolimbic pathway → positive symptoms.
- The dopamine hypothesis of schizophrenia suggests that excess dopamine activity in certain regions
cause positive symptoms (hallucinations and delusions), while low dopamine activity in other areas may
be responsible for negative and cognitive symptoms (lack of motivation and memory problems). This
theory is supported by evidence such as antipsychotic drugs blocking dopamine D2 receptors and drugs
that increase dopamine, like amphetamines trigger psychotic symptoms
Glutamate Dysfunction in Schizophrenia: Reduced NMDA receptor function is a hallmark.
- Hypofunction of glutamate: dysfunction in the glutamate system, particularly the NDMA receptor is a
key factor in schizophrenia
- NMDA receptor hypofunction: a central hypothesis is that reduced function of NMDA receptors,
particularly on GABA interneurons, leads to impaired inhibitory control. This can result in
overstimulation of dopamine pathways, contributing to positive symptoms of psychosis.
- Altered glutamate/glutamine cycling: dysfunction glutamate-glutamine cycling, possibly due to
astrocytic problems, could lead to imbalances in glutamate and glutamine levels impact synaptic activity
- Excitotoxicity: in chronic schizophrenia, elevated glutamate levels could lead to excitotoxic effects,
causing a degeneration of glutamatergic neurons over time, which would be reflected in lower glutamate
measures
