BARKLEY PMHNP ULTIMATE EXAM REVIEW QUESTIONS AND
ANSWERS |FALL 2025/2026 UPDATE | 100% CORRECT LATEST
Question: Which neurotransmitter is primarily implicated in the positive symptoms of
schizophrenia due to hyperactivity in the mesolimbic pathway? A. Serotonin B. Dopamine
C. GABA D. Glutamate Correct Answer: B Rationale: Dopamine hyperactivity in the
mesolimbic pathway is associated with positive symptoms (hallucinations, delusions) in
schizophrenia, per the dopamine hypothesis.
Question: A patient with major depressive disorder shows deficits in which monoamine
neurotransmitter systems? A. Dopamine and acetylcholine B. Serotonin, norepinephrine,
and dopamine C. GABA and glutamate D. Histamine and melatonin Correct Answer: B
Rationale: The monoamine hypothesis links depression to deficiencies in serotonin,
norepinephrine, and dopamine; many antidepressants target these systems.
Question: Negative symptoms of schizophrenia, such as avolition and flat affect, are most
associated with dysregulation of which neurotransmitter? A. Excess dopamine in the
mesocortical pathway B. Glutamate hypofunction C. Serotonin excess D. GABA
hyperactivity Correct Answer: B Rationale: Glutamate dysregulation (NMDA receptor
hypofunction) contributes to negative and cognitive symptoms in schizophrenia.
Question: Which brain structure is primarily involved in fear conditioning and emotional
processing in anxiety disorders? A. Hippocampus B. Amygdala C. Prefrontal cortex D.
Cerebellum Correct Answer: B Rationale: The amygdala processes fear responses and is
hyperactive in anxiety disorders.
Question: In Alzheimer's disease, which neurotransmitter deficiency is most prominent
and targeted by cholinesterase inhibitors? A. Dopamine B. Acetylcholine C. Serotonin D.
Norepinephrine Correct Answer: B Rationale: Acetylcholine deficiency in the basal
forebrain contributes to cognitive decline; donepezil and similar drugs inhibit its
breakdown.
,Question: Genetic factors account for approximately what percentage of heritability in
bipolar disorder? A. 10-20% B. 30-40% C. 60-80% D. Less than 10% Correct Answer: C
Rationale: Bipolar disorder has high heritability (60-80%), with multiple genes and
environmental interactions involved.
Question: Which cytochrome P450 enzyme is primarily responsible for metabolizing many
SSRIs, including fluoxetine and paroxetine? A. CYP1A2 B. CYP2D6 C. CYP3A4 D. CYP2C19
Correct Answer: B Rationale: CYP2D6 metabolizes many psychotropics; poor metabolizers
may experience increased side effects.
Question: The hypothalamic-pituitary-adrenal (HPA) axis dysregulation in chronic stress
leads to elevated levels of which hormone? A. Cortisol B. Insulin C. Thyroid hormone D.
Melatonin Correct Answer: A Rationale: Chronic stress activates the HPA axis, resulting in
hypercortisolemia, which contributes to depression and anxiety.
Question: In ADHD, which neurotransmitter deficits are primarily implicated in the
prefrontal cortex? A. Serotonin and GABA B. Dopamine and norepinephrine C. Glutamate
and acetylcholine D. Histamine and orexin Correct Answer: B Rationale: ADHD involves
hypofunction of dopamine and norepinephrine in prefrontal circuits affecting executive
function.
Question: Which genetic polymorphism is associated with reduced efficacy of clopidogrel
but also relevant in some psychiatric pharmacogenomics discussions? (Note: PMHNP
context often includes CYP testing.) A. CYP2D6 poor metabolizer B. HLA-B*1502 C. COMT
Val158Met D. BDNF Val66Met Correct Answer: A Rationale: CYP2D6 polymorphisms affect
metabolism of many antidepressants and antipsychotics.
Question: The primary excitatory neurotransmitter in the CNS is: A. GABA B. Glutamate
C. Glycine D. Dopamine Correct Answer: B Rationale: Glutamate is the main excitatory
neurotransmitter; dysregulation is linked to excitotoxicity in various disorders.
,Question: The primary inhibitory neurotransmitter in the brain is: A. Dopamine B.
Serotonin C. GABA D. Norepinephrine Correct Answer: C Rationale: GABA reduces
neuronal excitability; benzodiazepines enhance GABA activity for anxiety.
Question: In panic disorder, which brain region shows hyperactivity during attacks? A.
Hippocampus B. Amygdala and locus coeruleus C. Occipital lobe D. Basal ganglia Correct
Answer: B Rationale: The amygdala and noradrenergic locus coeruleus drive acute fear
responses.
Question: Heritability estimates for schizophrenia are approximately: A. 20-30% B. 40-50%
C. 70-80% D. 90-100% Correct Answer: C Rationale: Schizophrenia has high heritability
(~80%), involving polygenic risk.
Question: Which neurotransmitter is involved in reward pathways and addiction via the
mesolimbic system? A. Serotonin B. Dopamine C. Acetylcholine D. Glutamate Correct
Answer: B Rationale: Dopamine release in the nucleus accumbens mediates reward and
reinforcement.
Question: Which dopamine pathway is primarily associated with extrapyramidal side
effects from typical antipsychotics? A. Mesolimbic pathway B. Mesocortical pathway C.
Nigrostriatal pathway D. Tuberoinfundibular pathway Correct Answer: C Rationale: The
nigrostriatal pathway regulates motor function; blockade here by dopamine antagonists
causes EPS (e.g., dystonia, parkinsonism).
Question: In obsessive-compulsive disorder (OCD), hyperactivity is most noted in which
brain circuit? A. Cortico-striato-thalamo-cortical (CSTC) loop B. Limbic system C. Default
mode network D. Salience network Correct Answer: A Rationale: The CSTC circuit is
implicated in OCD, with overactivity leading to repetitive thoughts and behaviors; SSRIs
modulate this pathway.
Question: Which genetic factor is strongly associated with increased risk of tardive
dyskinesia in patients on long-term antipsychotics? A. CYP2D6 poor metabolizer B. DRD2
gene variants C. COMT Val158Met polymorphism D. BDNF Val66Met Correct Answer: B
, Rationale: DRD2 receptor gene variations influence susceptibility to tardive dyskinesia due
to altered dopamine signaling.
Question: The half-life of fluoxetine (Prozac) and its active metabolite norfluoxetine is
approximately: A. 4-6 hours B. 1-4 days for fluoxetine, up to 7-15 days for norfluoxetine C.
24 hours D. 12 hours Correct Answer: B Rationale: Fluoxetine has a long half-life (4-6 days),
and norfluoxetine up to 16 days, reducing withdrawal risk but increasing drug interaction
potential.
Question: Chronic HPA axis activation in PTSD leads to: A. Decreased cortisol levels B.
Hippocampal atrophy C. Reduced amygdala activity D. Increased prefrontal cortex volume
Correct Answer: B Rationale: Prolonged hypercortisolemia causes hippocampal volume
reduction, impairing memory and stress regulation.
Question: Which neurotransmitter system is primarily targeted by benzodiazepines for
anxiolytic effects? A. Dopaminergic B. Serotonergic C. GABAergic (GABA-A receptor
enhancement) D. Noradrenergic Correct Answer: C Rationale: Benzodiazepines potentiate
GABA at GABA-A receptors, increasing inhibitory tone to reduce anxiety.
Question: The Val158Met polymorphism in the COMT gene is associated with: A. Faster
dopamine breakdown in prefrontal cortex (Met allele = higher dopamine) B. Slower
serotonin reuptake C. Increased risk of schizophrenia only D. Reduced acetylcholine
synthesis Correct Answer: A Rationale: COMT Val allele metabolizes dopamine faster,
leading to lower prefrontal dopamine; Met allele preserves dopamine, linked to better
executive function but higher anxiety risk.
Question: In autism spectrum disorder, which brain region often shows atypical
connectivity? A. Amygdala B. Fusiform face area C. Corpus callosum D. All of the above
Correct Answer: D Rationale: ASD involves altered connectivity in social processing areas
(amygdala, fusiform), and white matter tracts like the corpus callosum.
Question: CYP3A4 is the primary enzyme metabolizing which common psychotropic?
A. Sertraline B. Quetiapine C. Lithium D. Lamotrigine Correct Answer: B Rationale:
ANSWERS |FALL 2025/2026 UPDATE | 100% CORRECT LATEST
Question: Which neurotransmitter is primarily implicated in the positive symptoms of
schizophrenia due to hyperactivity in the mesolimbic pathway? A. Serotonin B. Dopamine
C. GABA D. Glutamate Correct Answer: B Rationale: Dopamine hyperactivity in the
mesolimbic pathway is associated with positive symptoms (hallucinations, delusions) in
schizophrenia, per the dopamine hypothesis.
Question: A patient with major depressive disorder shows deficits in which monoamine
neurotransmitter systems? A. Dopamine and acetylcholine B. Serotonin, norepinephrine,
and dopamine C. GABA and glutamate D. Histamine and melatonin Correct Answer: B
Rationale: The monoamine hypothesis links depression to deficiencies in serotonin,
norepinephrine, and dopamine; many antidepressants target these systems.
Question: Negative symptoms of schizophrenia, such as avolition and flat affect, are most
associated with dysregulation of which neurotransmitter? A. Excess dopamine in the
mesocortical pathway B. Glutamate hypofunction C. Serotonin excess D. GABA
hyperactivity Correct Answer: B Rationale: Glutamate dysregulation (NMDA receptor
hypofunction) contributes to negative and cognitive symptoms in schizophrenia.
Question: Which brain structure is primarily involved in fear conditioning and emotional
processing in anxiety disorders? A. Hippocampus B. Amygdala C. Prefrontal cortex D.
Cerebellum Correct Answer: B Rationale: The amygdala processes fear responses and is
hyperactive in anxiety disorders.
Question: In Alzheimer's disease, which neurotransmitter deficiency is most prominent
and targeted by cholinesterase inhibitors? A. Dopamine B. Acetylcholine C. Serotonin D.
Norepinephrine Correct Answer: B Rationale: Acetylcholine deficiency in the basal
forebrain contributes to cognitive decline; donepezil and similar drugs inhibit its
breakdown.
,Question: Genetic factors account for approximately what percentage of heritability in
bipolar disorder? A. 10-20% B. 30-40% C. 60-80% D. Less than 10% Correct Answer: C
Rationale: Bipolar disorder has high heritability (60-80%), with multiple genes and
environmental interactions involved.
Question: Which cytochrome P450 enzyme is primarily responsible for metabolizing many
SSRIs, including fluoxetine and paroxetine? A. CYP1A2 B. CYP2D6 C. CYP3A4 D. CYP2C19
Correct Answer: B Rationale: CYP2D6 metabolizes many psychotropics; poor metabolizers
may experience increased side effects.
Question: The hypothalamic-pituitary-adrenal (HPA) axis dysregulation in chronic stress
leads to elevated levels of which hormone? A. Cortisol B. Insulin C. Thyroid hormone D.
Melatonin Correct Answer: A Rationale: Chronic stress activates the HPA axis, resulting in
hypercortisolemia, which contributes to depression and anxiety.
Question: In ADHD, which neurotransmitter deficits are primarily implicated in the
prefrontal cortex? A. Serotonin and GABA B. Dopamine and norepinephrine C. Glutamate
and acetylcholine D. Histamine and orexin Correct Answer: B Rationale: ADHD involves
hypofunction of dopamine and norepinephrine in prefrontal circuits affecting executive
function.
Question: Which genetic polymorphism is associated with reduced efficacy of clopidogrel
but also relevant in some psychiatric pharmacogenomics discussions? (Note: PMHNP
context often includes CYP testing.) A. CYP2D6 poor metabolizer B. HLA-B*1502 C. COMT
Val158Met D. BDNF Val66Met Correct Answer: A Rationale: CYP2D6 polymorphisms affect
metabolism of many antidepressants and antipsychotics.
Question: The primary excitatory neurotransmitter in the CNS is: A. GABA B. Glutamate
C. Glycine D. Dopamine Correct Answer: B Rationale: Glutamate is the main excitatory
neurotransmitter; dysregulation is linked to excitotoxicity in various disorders.
,Question: The primary inhibitory neurotransmitter in the brain is: A. Dopamine B.
Serotonin C. GABA D. Norepinephrine Correct Answer: C Rationale: GABA reduces
neuronal excitability; benzodiazepines enhance GABA activity for anxiety.
Question: In panic disorder, which brain region shows hyperactivity during attacks? A.
Hippocampus B. Amygdala and locus coeruleus C. Occipital lobe D. Basal ganglia Correct
Answer: B Rationale: The amygdala and noradrenergic locus coeruleus drive acute fear
responses.
Question: Heritability estimates for schizophrenia are approximately: A. 20-30% B. 40-50%
C. 70-80% D. 90-100% Correct Answer: C Rationale: Schizophrenia has high heritability
(~80%), involving polygenic risk.
Question: Which neurotransmitter is involved in reward pathways and addiction via the
mesolimbic system? A. Serotonin B. Dopamine C. Acetylcholine D. Glutamate Correct
Answer: B Rationale: Dopamine release in the nucleus accumbens mediates reward and
reinforcement.
Question: Which dopamine pathway is primarily associated with extrapyramidal side
effects from typical antipsychotics? A. Mesolimbic pathway B. Mesocortical pathway C.
Nigrostriatal pathway D. Tuberoinfundibular pathway Correct Answer: C Rationale: The
nigrostriatal pathway regulates motor function; blockade here by dopamine antagonists
causes EPS (e.g., dystonia, parkinsonism).
Question: In obsessive-compulsive disorder (OCD), hyperactivity is most noted in which
brain circuit? A. Cortico-striato-thalamo-cortical (CSTC) loop B. Limbic system C. Default
mode network D. Salience network Correct Answer: A Rationale: The CSTC circuit is
implicated in OCD, with overactivity leading to repetitive thoughts and behaviors; SSRIs
modulate this pathway.
Question: Which genetic factor is strongly associated with increased risk of tardive
dyskinesia in patients on long-term antipsychotics? A. CYP2D6 poor metabolizer B. DRD2
gene variants C. COMT Val158Met polymorphism D. BDNF Val66Met Correct Answer: B
, Rationale: DRD2 receptor gene variations influence susceptibility to tardive dyskinesia due
to altered dopamine signaling.
Question: The half-life of fluoxetine (Prozac) and its active metabolite norfluoxetine is
approximately: A. 4-6 hours B. 1-4 days for fluoxetine, up to 7-15 days for norfluoxetine C.
24 hours D. 12 hours Correct Answer: B Rationale: Fluoxetine has a long half-life (4-6 days),
and norfluoxetine up to 16 days, reducing withdrawal risk but increasing drug interaction
potential.
Question: Chronic HPA axis activation in PTSD leads to: A. Decreased cortisol levels B.
Hippocampal atrophy C. Reduced amygdala activity D. Increased prefrontal cortex volume
Correct Answer: B Rationale: Prolonged hypercortisolemia causes hippocampal volume
reduction, impairing memory and stress regulation.
Question: Which neurotransmitter system is primarily targeted by benzodiazepines for
anxiolytic effects? A. Dopaminergic B. Serotonergic C. GABAergic (GABA-A receptor
enhancement) D. Noradrenergic Correct Answer: C Rationale: Benzodiazepines potentiate
GABA at GABA-A receptors, increasing inhibitory tone to reduce anxiety.
Question: The Val158Met polymorphism in the COMT gene is associated with: A. Faster
dopamine breakdown in prefrontal cortex (Met allele = higher dopamine) B. Slower
serotonin reuptake C. Increased risk of schizophrenia only D. Reduced acetylcholine
synthesis Correct Answer: A Rationale: COMT Val allele metabolizes dopamine faster,
leading to lower prefrontal dopamine; Met allele preserves dopamine, linked to better
executive function but higher anxiety risk.
Question: In autism spectrum disorder, which brain region often shows atypical
connectivity? A. Amygdala B. Fusiform face area C. Corpus callosum D. All of the above
Correct Answer: D Rationale: ASD involves altered connectivity in social processing areas
(amygdala, fusiform), and white matter tracts like the corpus callosum.
Question: CYP3A4 is the primary enzyme metabolizing which common psychotropic?
A. Sertraline B. Quetiapine C. Lithium D. Lamotrigine Correct Answer: B Rationale:
