1
BARKLEY PMHNP COMPREHENSIVE BOARD
REVIEW EXAM 175 Certification-Style Questions
with Detailed Answers
SECTION 1: NEUROBIOLOGY & NEUROTRANSMITTERS (Questions 1–20)
1. A 45-year-old patient with schizophrenia has predominantly negative
symptoms. Dysfunction in which dopamine pathway is most associated with
these symptoms?
A. Mesolimbic pathway
B. Mesocortical pathway
C. Nigrostriatal pathway
D. Tuberoinfundibular pathway
Answer: B
Rationale: The mesocortical pathway projects from the ventral tegmental area to
the prefrontal cortex. Decreased dopamine in this pathway is linked to negative
symptoms (apathy, alogia, affective flattening) and cognitive deficits. Positive
symptoms are associated with hyperactivity in the mesolimbic pathway. The
nigrostriatal pathway relates to movement (Parkinsonism when blocked), and the
tuberoinfundibular pathway regulates prolactin.
2. A patient with major depressive disorder has been on fluoxetine for 8 weeks
without response. The PMHNP considers adding bupropion. Which
neurotransmitter systems are primarily targeted by this combination?
A. Serotonin and dopamine
B. Serotonin and norepinephrine
C. Serotonin, norepinephrine, and dopamine
D. Dopamine and norepinephrine
Answer: C
Rationale: Fluoxetine (SSRI) blocks serotonin reuptake. Bupropion blocks
pg. 1
,2
norepinephrine and dopamine reuptake (NDRI). The combination enhances all
three monoamine systems, which may improve treatment-resistant depression.
3. Which receptor is primarily responsible for the anxiolytic effects of
benzodiazepines?
A. GABA-B
B. GABA-A (alpha-1 subunit)
C. GABA-A (alpha-2 and alpha-3 subunits)
D. Glutamate NMDA
Answer: C
Rationale: Benzodiazepines bind to GABA-A receptors at the interface of alpha
and gamma subunits. The alpha-2 and alpha-3 subunits mediate anxiolysis, while
the alpha-1 subunit mediates sedation, amnesia, and anticonvulsant effects. Non-
selective benzodiazepines affect all.
4. Clozapine is associated with a lower risk of extrapyramidal symptoms due to
which property?
A. High D2 receptor blockade
B. Fast D2 receptor dissociation and high 5-HT2A antagonism
C. Dopamine D1 agonism
D. Anticholinergic activity
Answer: B
Rationale: Clozapine has low D2 affinity and dissociates rapidly from the D2
receptor, which limits striatal D2 blockade. It also has high 5-HT2A antagonism,
which may reduce EPS. It has strong anticholinergic effects, but the primary
reason for low EPS is its unique D2 binding kinetics.
5. Which neurotransmitter is primarily responsible for the regulation of the
hypothalamic-pituitary-adrenal (HPA) axis stress response?
A. Dopamine
B. Corticotropin-releasing hormone (CRH)
pg. 2
,3
C. Acetylcholine
D. GABA
Answer: B
Rationale: CRH is the central driver of the HPA axis, stimulating pituitary ACTH
release and subsequent cortisol production. Dysregulation is implicated in
depression and PTSD.
6. A patient with Alzheimer's disease is started on donepezil. What is the
primary therapeutic mechanism?
A. NMDA receptor antagonism
B. Acetylcholinesterase inhibition
C. MAO-B inhibition
D. GABA agonism
Answer: B
Rationale: Donepezil inhibits acetylcholinesterase, increasing synaptic
acetylcholine and modestly improving cognition.
7. Which of the following is a common effect of long-term benzodiazepine use
on GABA-A receptors?
A. Upregulation
B. Downregulation (reduced receptor number/sensitivity)
C. Increased receptor affinity
D. No change
Answer: B
Rationale: Chronic benzodiazepine use leads to tolerance due to downregulation
of GABA-A receptors, contributing to withdrawal symptoms.
8. The therapeutic action of lithium in bipolar disorder is partly attributed to
inhibition of which enzyme?
A. Monoamine oxidase
B. Glycogen synthase kinase-3 (GSK-3)
pg. 3
, 4
C. Acetylcholinesterase
D. Tyrosine hydroxylase
Answer: B
Rationale: Lithium inhibits GSK-3, an enzyme involved in cellular signaling,
circadian rhythms, and neuroprotection. It also inhibits inositol
monophosphatase, affecting the phosphoinositide pathway.
9. Which brain region is most responsible for emotional memory and fear
conditioning?
A. Hippocampus
B. Amygdala
C. Prefrontal cortex
D. Thalamus
Answer: B
Rationale: The amygdala is central to processing fear and emotional memories. It
is hyperactive in PTSD and anxiety disorders. The hippocampus consolidates
declarative memory.
10. A patient on venlafaxine develops hypertension. At high doses, which
neurotransmitter activity explains this effect?
A. Increased serotonin
B. Increased norepinephrine reuptake inhibition
C. Dopamine agonism
D. Anticholinergic effects
Answer: B
Rationale: At higher doses (>150 mg/day), venlafaxine inhibits norepinephrine
reuptake, which can lead to increased sympathetic tone and elevated blood
pressure.
11. The primary inhibitory neurotransmitter in the brain is:
A. Glutamate
pg. 4
BARKLEY PMHNP COMPREHENSIVE BOARD
REVIEW EXAM 175 Certification-Style Questions
with Detailed Answers
SECTION 1: NEUROBIOLOGY & NEUROTRANSMITTERS (Questions 1–20)
1. A 45-year-old patient with schizophrenia has predominantly negative
symptoms. Dysfunction in which dopamine pathway is most associated with
these symptoms?
A. Mesolimbic pathway
B. Mesocortical pathway
C. Nigrostriatal pathway
D. Tuberoinfundibular pathway
Answer: B
Rationale: The mesocortical pathway projects from the ventral tegmental area to
the prefrontal cortex. Decreased dopamine in this pathway is linked to negative
symptoms (apathy, alogia, affective flattening) and cognitive deficits. Positive
symptoms are associated with hyperactivity in the mesolimbic pathway. The
nigrostriatal pathway relates to movement (Parkinsonism when blocked), and the
tuberoinfundibular pathway regulates prolactin.
2. A patient with major depressive disorder has been on fluoxetine for 8 weeks
without response. The PMHNP considers adding bupropion. Which
neurotransmitter systems are primarily targeted by this combination?
A. Serotonin and dopamine
B. Serotonin and norepinephrine
C. Serotonin, norepinephrine, and dopamine
D. Dopamine and norepinephrine
Answer: C
Rationale: Fluoxetine (SSRI) blocks serotonin reuptake. Bupropion blocks
pg. 1
,2
norepinephrine and dopamine reuptake (NDRI). The combination enhances all
three monoamine systems, which may improve treatment-resistant depression.
3. Which receptor is primarily responsible for the anxiolytic effects of
benzodiazepines?
A. GABA-B
B. GABA-A (alpha-1 subunit)
C. GABA-A (alpha-2 and alpha-3 subunits)
D. Glutamate NMDA
Answer: C
Rationale: Benzodiazepines bind to GABA-A receptors at the interface of alpha
and gamma subunits. The alpha-2 and alpha-3 subunits mediate anxiolysis, while
the alpha-1 subunit mediates sedation, amnesia, and anticonvulsant effects. Non-
selective benzodiazepines affect all.
4. Clozapine is associated with a lower risk of extrapyramidal symptoms due to
which property?
A. High D2 receptor blockade
B. Fast D2 receptor dissociation and high 5-HT2A antagonism
C. Dopamine D1 agonism
D. Anticholinergic activity
Answer: B
Rationale: Clozapine has low D2 affinity and dissociates rapidly from the D2
receptor, which limits striatal D2 blockade. It also has high 5-HT2A antagonism,
which may reduce EPS. It has strong anticholinergic effects, but the primary
reason for low EPS is its unique D2 binding kinetics.
5. Which neurotransmitter is primarily responsible for the regulation of the
hypothalamic-pituitary-adrenal (HPA) axis stress response?
A. Dopamine
B. Corticotropin-releasing hormone (CRH)
pg. 2
,3
C. Acetylcholine
D. GABA
Answer: B
Rationale: CRH is the central driver of the HPA axis, stimulating pituitary ACTH
release and subsequent cortisol production. Dysregulation is implicated in
depression and PTSD.
6. A patient with Alzheimer's disease is started on donepezil. What is the
primary therapeutic mechanism?
A. NMDA receptor antagonism
B. Acetylcholinesterase inhibition
C. MAO-B inhibition
D. GABA agonism
Answer: B
Rationale: Donepezil inhibits acetylcholinesterase, increasing synaptic
acetylcholine and modestly improving cognition.
7. Which of the following is a common effect of long-term benzodiazepine use
on GABA-A receptors?
A. Upregulation
B. Downregulation (reduced receptor number/sensitivity)
C. Increased receptor affinity
D. No change
Answer: B
Rationale: Chronic benzodiazepine use leads to tolerance due to downregulation
of GABA-A receptors, contributing to withdrawal symptoms.
8. The therapeutic action of lithium in bipolar disorder is partly attributed to
inhibition of which enzyme?
A. Monoamine oxidase
B. Glycogen synthase kinase-3 (GSK-3)
pg. 3
, 4
C. Acetylcholinesterase
D. Tyrosine hydroxylase
Answer: B
Rationale: Lithium inhibits GSK-3, an enzyme involved in cellular signaling,
circadian rhythms, and neuroprotection. It also inhibits inositol
monophosphatase, affecting the phosphoinositide pathway.
9. Which brain region is most responsible for emotional memory and fear
conditioning?
A. Hippocampus
B. Amygdala
C. Prefrontal cortex
D. Thalamus
Answer: B
Rationale: The amygdala is central to processing fear and emotional memories. It
is hyperactive in PTSD and anxiety disorders. The hippocampus consolidates
declarative memory.
10. A patient on venlafaxine develops hypertension. At high doses, which
neurotransmitter activity explains this effect?
A. Increased serotonin
B. Increased norepinephrine reuptake inhibition
C. Dopamine agonism
D. Anticholinergic effects
Answer: B
Rationale: At higher doses (>150 mg/day), venlafaxine inhibits norepinephrine
reuptake, which can lead to increased sympathetic tone and elevated blood
pressure.
11. The primary inhibitory neurotransmitter in the brain is:
A. Glutamate
pg. 4
