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NURS 660 Exam 1 Study Guide - PMHNP
Exam 1 Review
Pathways in schizophrenia
• Brain imaging shows cerebral atrophy and enlarged fluid filled ventricles, as well
as shrinkage in prefrontal cortex, temporal, basal ganglia, and limbic regions like
hippocampus.
• Five dopamine pathways in the brain. The neuroanatomy of dopamine neuronal pathways
in the brain can explain the symptoms of schizophrenia as well as the therapeutic effects
and side effects of antipsychotic drugs.
Know different pathways in the brain
• The nigrostriatal dopamine pathway, which projects from the substantia nigra to the
basal ganglia or striatum, is part of the extrapyramidal nervous system and controls motor
function and movement. When dopamine is deficient, it can cause parkinsonism with
tremor, rigidity, and akinesia/bradykinesia. When DA is in excess, it can cause
hyperkinetic movements such as tics and dyskinesias. In untreated schizophrenia,
activation of this pathway is believed to be “normal.”
• The mesolimbic dopamine pathway projects from the midbrain ventral tegmental area
to the nucleus accumbens, a part of the limbic system of the brain thought to be involved
in many behaviors such as pleasurable sensations, the powerful euphoria of drugs of
abuse, as well as delusions and hallucinations of psychosis. Hyperactivity of dopamine
neurons in the mesolimbic dopamine pathway theoretically mediates the positive
symptoms of psychosis such as delusions and hallucinations. This pathway is also
involved in pleasure, reward, and reinforcing behavior, and many drugs of abuse interact
here.
• The mesocortical dopamine pathway also projects from the midbrain ventral tegmental
area but sends its axons to areas of the prefrontal cortex, where they may have a role in
mediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) and affective
symptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia. Expression of
these symptoms is thought to be associated with hypoactivity of this pathway.
• The tuberoinfundibular dopamine pathway projects from the hypothalamus to the
anterior pituitary gland and controls prolactin secretion into the circulation. Dopamine
inhibits prolactin secretion. In untreated schizophrenia, activation of this pathway is
believed to be “normal.”.
• The thalamic dopamine pathway arises from multiple sites, including the
periaqueductal gray, ventral mesencephalon, hypothalamic nuclei, and lateral
parabrachial nucleus, and it projects to the thalamus. Its function is not currently well
known but may be involved in sleep and arousal mechanisms by gating information
,2
passing through the thalamus to the cortex and other brain areas. There is no evidence at
this point for abnormal functioning of this dopamine pathway in schizophrenia.
GLUTAMATE
• Excitatory NT, can excite and turn on all virtually ALL CNS neurons. Known as
the master switch
• Glutamate is released from synaptic vesicles, interacts with neighbor cells (glia) is taken
up into glia VIA excitatory amino acid transporters (EAATs), it is converted to glutamine
inside glia by enzyme glutamine synthetase, glutamine is released and SNAT (specific
neutral amino acid transporters) takes it back into presynaptic neuron where its converted
back to glutamate, then goes back into synaptic vesicles by vGluT transporters to be
stored.
• NMDA receptors are glutamate receptors and requires cotransmitter glycine or d-serine,
made by neighboring glial cells (some neurons make glycine to put in synaptic vesicle
but most comes from glial cells). Glial cells convert l-serine to d-serine
Glutamate receptors:
• NMDA, AMPA, and kainite- these are all ionotropic. So glutamate is released, attaches to
receptor, sodium channels open and depolarize the cell, glutamate flows in, then Gaba is
released.
Glutamate pathways:
• Cortico-brainstem-descending projects from cortical pyramidal neurons to brainstem NT
centers including raphe for serotonin, VTA and substantia nigra for dopamine, ad locus
coeruleus for NE. These excitatory cortico brainstem neurons stimulate NT release.
• Corticostriatal-descending from cortical pyramidal neurons to striatal complex. AKA
cortico-accumbens when project to NA. These neurons terminate on GABA neurons.
• Hippocampal accumbens-projects from hippocampus to NA-this path is linked to schizo.
• Thalamo-cortical pathways-brings info from thalamus back to cortex to process sensory
info.
• Corticothalamic-projets back to thalamus
• Cortico-cortical-glutamate pathways in cortex
• Indirect cortico-cortico-one neuron inhibit another neuron via interneurons that release
GABA.
Positive and negative symptoms of Schizophrenia
• Positive symptoms: these are psychotic behaviors that are not generally seen in healthy
individuals. Those with positive symptoms may lose touch with some aspects of reality.
Symptoms: delusions, hallucinations, thought disorders (unusual or dysfunctional ways
, 3
of thinking), movement disorder (agitated body movements) (Arising from the
mesolimbic dopamine pathway)
i. Positive symptoms of schizophrenia are hypothetically modulated by
malfunctioning mesolimbic circuits.
1. Delusions, Hallucinations, Distortions or exaggerations in
language and communication, Disorganized speech,
Disorganized behavior, Catatonic behavior, and Agitation
• Negative symptoms: disruptions to normal emotions and behaviors. Characterized by:
flat affect, reduced feelings of pleasure in everyday life, difficulty beginning and
sustaining activities, decreased communication. (Arising from the mesocortical dopamine
pathway)
ii. Negative symptoms are hypothetically linked to malfunctioning
mesocortical circuits and may also involve mesolimbic regions such as
the nucleus accumbens.
1. Alogia – Poverty of speech; e.g., talks little, uses few words
2. Affective blunting – Reduced range of emotions (perception,
experience and expression); e.g., feels numb or empty inside,
recalls few emotional experiences, good or bad
3. Asociality – Reduced social drive and interaction; e.g., little sexual
interest, few friends, little interest in spending time with (or little
time spent with) friends
4. Anhedonia – Reduced ability to experience pleasure; e.g., finds
previous hobbies or interests unpleasurable
5. Avolition – Reduced desire, motivation, persistence; e.g.,
reduced ability to undertake and complete everyday tasks; may
have poor personal hygiene
iii. Affective symptoms of schizophrenia
1. Affective symptoms are associated with the
ventromedial prefrontal cortex.
a. Depressed mood, Anxious mood, Guilt, Tension,
Irritability, and Worry
iv. Cognitive symptoms of schizophrenia
1. Cognitive symptoms are associated with problematic
information processing in the dorsolateral prefrontal cortex.
a. Problems representing and maintaining goals, Problems
allocating attentional resources, Problems focusing and
sustaining attention , Problems evaluating functions ,
Problems modulating behavior based upon social cues,
Problems monitoring performance , Problems prioritizing ,
Problems with serial learning, Impaired verbal fluency,
and Difficulty with problem solving
NURS 660 Exam 1 Study Guide - PMHNP
Exam 1 Review
Pathways in schizophrenia
• Brain imaging shows cerebral atrophy and enlarged fluid filled ventricles, as well
as shrinkage in prefrontal cortex, temporal, basal ganglia, and limbic regions like
hippocampus.
• Five dopamine pathways in the brain. The neuroanatomy of dopamine neuronal pathways
in the brain can explain the symptoms of schizophrenia as well as the therapeutic effects
and side effects of antipsychotic drugs.
Know different pathways in the brain
• The nigrostriatal dopamine pathway, which projects from the substantia nigra to the
basal ganglia or striatum, is part of the extrapyramidal nervous system and controls motor
function and movement. When dopamine is deficient, it can cause parkinsonism with
tremor, rigidity, and akinesia/bradykinesia. When DA is in excess, it can cause
hyperkinetic movements such as tics and dyskinesias. In untreated schizophrenia,
activation of this pathway is believed to be “normal.”
• The mesolimbic dopamine pathway projects from the midbrain ventral tegmental area
to the nucleus accumbens, a part of the limbic system of the brain thought to be involved
in many behaviors such as pleasurable sensations, the powerful euphoria of drugs of
abuse, as well as delusions and hallucinations of psychosis. Hyperactivity of dopamine
neurons in the mesolimbic dopamine pathway theoretically mediates the positive
symptoms of psychosis such as delusions and hallucinations. This pathway is also
involved in pleasure, reward, and reinforcing behavior, and many drugs of abuse interact
here.
• The mesocortical dopamine pathway also projects from the midbrain ventral tegmental
area but sends its axons to areas of the prefrontal cortex, where they may have a role in
mediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) and affective
symptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia. Expression of
these symptoms is thought to be associated with hypoactivity of this pathway.
• The tuberoinfundibular dopamine pathway projects from the hypothalamus to the
anterior pituitary gland and controls prolactin secretion into the circulation. Dopamine
inhibits prolactin secretion. In untreated schizophrenia, activation of this pathway is
believed to be “normal.”.
• The thalamic dopamine pathway arises from multiple sites, including the
periaqueductal gray, ventral mesencephalon, hypothalamic nuclei, and lateral
parabrachial nucleus, and it projects to the thalamus. Its function is not currently well
known but may be involved in sleep and arousal mechanisms by gating information
,2
passing through the thalamus to the cortex and other brain areas. There is no evidence at
this point for abnormal functioning of this dopamine pathway in schizophrenia.
GLUTAMATE
• Excitatory NT, can excite and turn on all virtually ALL CNS neurons. Known as
the master switch
• Glutamate is released from synaptic vesicles, interacts with neighbor cells (glia) is taken
up into glia VIA excitatory amino acid transporters (EAATs), it is converted to glutamine
inside glia by enzyme glutamine synthetase, glutamine is released and SNAT (specific
neutral amino acid transporters) takes it back into presynaptic neuron where its converted
back to glutamate, then goes back into synaptic vesicles by vGluT transporters to be
stored.
• NMDA receptors are glutamate receptors and requires cotransmitter glycine or d-serine,
made by neighboring glial cells (some neurons make glycine to put in synaptic vesicle
but most comes from glial cells). Glial cells convert l-serine to d-serine
Glutamate receptors:
• NMDA, AMPA, and kainite- these are all ionotropic. So glutamate is released, attaches to
receptor, sodium channels open and depolarize the cell, glutamate flows in, then Gaba is
released.
Glutamate pathways:
• Cortico-brainstem-descending projects from cortical pyramidal neurons to brainstem NT
centers including raphe for serotonin, VTA and substantia nigra for dopamine, ad locus
coeruleus for NE. These excitatory cortico brainstem neurons stimulate NT release.
• Corticostriatal-descending from cortical pyramidal neurons to striatal complex. AKA
cortico-accumbens when project to NA. These neurons terminate on GABA neurons.
• Hippocampal accumbens-projects from hippocampus to NA-this path is linked to schizo.
• Thalamo-cortical pathways-brings info from thalamus back to cortex to process sensory
info.
• Corticothalamic-projets back to thalamus
• Cortico-cortical-glutamate pathways in cortex
• Indirect cortico-cortico-one neuron inhibit another neuron via interneurons that release
GABA.
Positive and negative symptoms of Schizophrenia
• Positive symptoms: these are psychotic behaviors that are not generally seen in healthy
individuals. Those with positive symptoms may lose touch with some aspects of reality.
Symptoms: delusions, hallucinations, thought disorders (unusual or dysfunctional ways
, 3
of thinking), movement disorder (agitated body movements) (Arising from the
mesolimbic dopamine pathway)
i. Positive symptoms of schizophrenia are hypothetically modulated by
malfunctioning mesolimbic circuits.
1. Delusions, Hallucinations, Distortions or exaggerations in
language and communication, Disorganized speech,
Disorganized behavior, Catatonic behavior, and Agitation
• Negative symptoms: disruptions to normal emotions and behaviors. Characterized by:
flat affect, reduced feelings of pleasure in everyday life, difficulty beginning and
sustaining activities, decreased communication. (Arising from the mesocortical dopamine
pathway)
ii. Negative symptoms are hypothetically linked to malfunctioning
mesocortical circuits and may also involve mesolimbic regions such as
the nucleus accumbens.
1. Alogia – Poverty of speech; e.g., talks little, uses few words
2. Affective blunting – Reduced range of emotions (perception,
experience and expression); e.g., feels numb or empty inside,
recalls few emotional experiences, good or bad
3. Asociality – Reduced social drive and interaction; e.g., little sexual
interest, few friends, little interest in spending time with (or little
time spent with) friends
4. Anhedonia – Reduced ability to experience pleasure; e.g., finds
previous hobbies or interests unpleasurable
5. Avolition – Reduced desire, motivation, persistence; e.g.,
reduced ability to undertake and complete everyday tasks; may
have poor personal hygiene
iii. Affective symptoms of schizophrenia
1. Affective symptoms are associated with the
ventromedial prefrontal cortex.
a. Depressed mood, Anxious mood, Guilt, Tension,
Irritability, and Worry
iv. Cognitive symptoms of schizophrenia
1. Cognitive symptoms are associated with problematic
information processing in the dorsolateral prefrontal cortex.
a. Problems representing and maintaining goals, Problems
allocating attentional resources, Problems focusing and
sustaining attention , Problems evaluating functions ,
Problems modulating behavior based upon social cues,
Problems monitoring performance , Problems prioritizing ,
Problems with serial learning, Impaired verbal fluency,
and Difficulty with problem solving
