ANCC Psychiatric–Mental Health Nurse Practitioner Board Certification Final Examination 2026:
Comprehensive Review of Psychopharmacology, Neurobiology, Psychotherapy, Ethics, Law,
Differential Diagnosis, and Advanced Clinical Practice Guidelines
Questions 1–150 (Multiple Answers + Detailed Explanations)
Section 1: Neurobiology & Pathophysiology (Q1–15)
Q1. Which neurotransmitters are implicated in the pathophysiology of major depressive disorder
(MDD)? (Select all that apply)
A) Serotonin
B) Norepinephrine
C) Dopamine
D) GABA
E) Glutamate
Answer: A, B, C, E
Explanation: MDD involves dysregulation of monoamines (serotonin, norepinephrine, dopamine) as
well as glutamatergic dysfunction. GABA is primarily inhibitory and more directly linked to anxiety
disorders, though indirect roles exist.
Q2. In Alzheimer’s disease, which neuropathological findings are characteristic? (Select all that apply)
A) Lewy bodies
B) Amyloid-beta plaques
C) Neurofibrillary tangles (tau protein)
D) Neuronal loss in nucleus basalis of Meynert
E) Dopamine depletion in substantia nigra
Answer: B, C, D
Explanation: Amyloid plaques and tau tangles are hallmarks. Loss of cholinergic neurons in nucleus
basalis of Meynert is common. Lewy bodies are seen in dementia with Lewy bodies; dopamine
depletion is Parkinson’s.
Q3. Which of the following are associated with increased glutamate activity in psychiatric
disorders? (Select all that apply)
A) Schizophrenia
B) Autism spectrum disorder
C) Hepatic encephalopathy
, D) Bipolar depression
E) Panic disorder
Answer: A, B, D
Explanation: Glutamate excess via NMDA receptor hypofunction is implicated in schizophrenia
(hyperglutamatergic state in some circuits). Autism and bipolar depression also show glutamatergic
dysregulation. Hepatic encephalopathy involves ammonia, not primarily glutamate excess; panic
disorder involves GABA/NE more than glutamate.
Q4. The hypothalamic–pituitary–adrenal (HPA) axis dysregulation is classically described in which
disorders? (Select all that apply)
A) PTSD
B) Cushing’s syndrome
C) Melancholic depression
D) Generalized anxiety disorder
E) Catatonia
Answer: A, B, C
Explanation: PTSD and melancholic depression show cortisol elevation and dexamethasone
nonsuppression. Cushing’s syndrome is hypercortisolism. GAD and catatonia are less consistently
linked to HPA axis changes.
Q5. Which brain regions show reduced volume in chronic schizophrenia? (Select all that apply)
A) Hippocampus
B) Amygdala
C) Thalamus
D) Prefrontal cortex
E) Cerebellum
Answer: A, C, D
Explanation: Hippocampal, thalamic, and prefrontal cortical volume loss is well-documented in
schizophrenia. Amygdala changes are inconsistent; cerebellum is less affected in typical schizophrenia
but may show changes in some subtypes.
Q6. Which of the following are characteristic of neuroleptic malignant syndrome (NMS)? (Select all that
apply)
A) Lead-pipe rigidity
B) Hyperpyrexia (fever)
C) Autonomic instability (tachycardia, labile BP)
D) Elevated creatine kinase (CK)
E) Tremor improving with anticholinergics
,Answer: A, B, C, D
Explanation: NMS presents with rigidity, fever, autonomic instability, and elevated CK. Tremor in NMS
does not improve with anticholinergics (unlike EPS). Treatment includes supportive care, dantrolene, or
bromocriptine.
Q7. Which neurotransmitter systems are primarily affected by cholinesterase inhibitors (e.g.,
donepezil)? (Select all that apply)
A) Acetylcholine
B) Dopamine
C) Norepinephrine
D) Serotonin
E) Glutamate
Answer: A only
Explanation: Cholinesterase inhibitors increase acetylcholine by preventing its breakdown. They have
indirect effects on other systems, but the primary direct action is on cholinergic transmission.
Q8. The mesolimbic pathway is involved in which functions? (Select all that apply)
A) Reward processing
B) Positive symptoms of schizophrenia
C) Motor coordination
D) Endocrine regulation
E) Addiction
Answer: A, B, E
Explanation: Mesolimbic (VTA to nucleus accumbens) mediates reward, addiction, and positive
symptoms (e.g., hallucinations, delusions) when hyperactive. Motor coordination is basal ganglia;
endocrine is tuberoinfundibular.
Q9. Which of the following are associated with reduced brain-derived neurotrophic factor (BDNF)
levels? (Select all that apply)
A) Major depression
B) Chronic stress
C) Antidepressant response
D) Hippocampal atrophy
E) Ketamine administration
Answer: A, B, D
Explanation: Depression and chronic stress lower BDNF, contributing to hippocampal atrophy.
Antidepressant response and ketamine increase BDNF (neurotrophic hypothesis).
Q10. Which statements about the default mode network (DMN) are correct? (Select all that apply)
, A) Active during mind-wandering and self-referential thought
B) Hyperactive in depression and anxiety
C) Deactivated during focused tasks
D) Involved in auditory processing
E) Abnormal in PTSD and schizophrenia
Answer: A, B, C, E
Explanation: DMN is active at rest, deactivated during tasks. Hyperactivity is seen in depression
(rumination), anxiety, PTSD, and schizophrenia (thought disorder). Auditory processing is primarily
temporal lobe.
Q11. Which genetic polymorphisms are associated with antipsychotic-induced weight gain? (Select all
that apply)
A) HTR2C (serotonin 2C receptor)
B) MC4R (melanocortin-4 receptor)
C) COMT Val158Met
D) SLC6A4 (serotonin transporter)
E) DRD2 Taq1A
Answer: A, B
Explanation: HTR2C and MC4R variants are consistently linked to antipsychotic-induced weight gain.
COMT and SLC6A4 are more linked to antipsychotic response and side effects (EPS, tardive dyskinesia)
rather than weight.
Q12. Which of the following are characteristic findings in hepatic encephalopathy? (Select all that
apply)
A) Asterixis (liver flap)
B) Elevated ammonia levels
C) Psychomotor slowing
D) Manic symptoms
E) EEG showing triphasic waves
Answer: A, B, C, E
Explanation: Hepatic encephalopathy presents with asterixis, elevated ammonia, cognitive slowing,
and triphasic waves on EEG. Manic symptoms are not typical; delirium or coma occurs in advanced
stages.
Q13. Which neuroimaging findings are associated with late-life depression? (Select all that apply)
A) White matter hyperintensities
B) Hippocampal atrophy
C) Increased prefrontal gray matter
Comprehensive Review of Psychopharmacology, Neurobiology, Psychotherapy, Ethics, Law,
Differential Diagnosis, and Advanced Clinical Practice Guidelines
Questions 1–150 (Multiple Answers + Detailed Explanations)
Section 1: Neurobiology & Pathophysiology (Q1–15)
Q1. Which neurotransmitters are implicated in the pathophysiology of major depressive disorder
(MDD)? (Select all that apply)
A) Serotonin
B) Norepinephrine
C) Dopamine
D) GABA
E) Glutamate
Answer: A, B, C, E
Explanation: MDD involves dysregulation of monoamines (serotonin, norepinephrine, dopamine) as
well as glutamatergic dysfunction. GABA is primarily inhibitory and more directly linked to anxiety
disorders, though indirect roles exist.
Q2. In Alzheimer’s disease, which neuropathological findings are characteristic? (Select all that apply)
A) Lewy bodies
B) Amyloid-beta plaques
C) Neurofibrillary tangles (tau protein)
D) Neuronal loss in nucleus basalis of Meynert
E) Dopamine depletion in substantia nigra
Answer: B, C, D
Explanation: Amyloid plaques and tau tangles are hallmarks. Loss of cholinergic neurons in nucleus
basalis of Meynert is common. Lewy bodies are seen in dementia with Lewy bodies; dopamine
depletion is Parkinson’s.
Q3. Which of the following are associated with increased glutamate activity in psychiatric
disorders? (Select all that apply)
A) Schizophrenia
B) Autism spectrum disorder
C) Hepatic encephalopathy
, D) Bipolar depression
E) Panic disorder
Answer: A, B, D
Explanation: Glutamate excess via NMDA receptor hypofunction is implicated in schizophrenia
(hyperglutamatergic state in some circuits). Autism and bipolar depression also show glutamatergic
dysregulation. Hepatic encephalopathy involves ammonia, not primarily glutamate excess; panic
disorder involves GABA/NE more than glutamate.
Q4. The hypothalamic–pituitary–adrenal (HPA) axis dysregulation is classically described in which
disorders? (Select all that apply)
A) PTSD
B) Cushing’s syndrome
C) Melancholic depression
D) Generalized anxiety disorder
E) Catatonia
Answer: A, B, C
Explanation: PTSD and melancholic depression show cortisol elevation and dexamethasone
nonsuppression. Cushing’s syndrome is hypercortisolism. GAD and catatonia are less consistently
linked to HPA axis changes.
Q5. Which brain regions show reduced volume in chronic schizophrenia? (Select all that apply)
A) Hippocampus
B) Amygdala
C) Thalamus
D) Prefrontal cortex
E) Cerebellum
Answer: A, C, D
Explanation: Hippocampal, thalamic, and prefrontal cortical volume loss is well-documented in
schizophrenia. Amygdala changes are inconsistent; cerebellum is less affected in typical schizophrenia
but may show changes in some subtypes.
Q6. Which of the following are characteristic of neuroleptic malignant syndrome (NMS)? (Select all that
apply)
A) Lead-pipe rigidity
B) Hyperpyrexia (fever)
C) Autonomic instability (tachycardia, labile BP)
D) Elevated creatine kinase (CK)
E) Tremor improving with anticholinergics
,Answer: A, B, C, D
Explanation: NMS presents with rigidity, fever, autonomic instability, and elevated CK. Tremor in NMS
does not improve with anticholinergics (unlike EPS). Treatment includes supportive care, dantrolene, or
bromocriptine.
Q7. Which neurotransmitter systems are primarily affected by cholinesterase inhibitors (e.g.,
donepezil)? (Select all that apply)
A) Acetylcholine
B) Dopamine
C) Norepinephrine
D) Serotonin
E) Glutamate
Answer: A only
Explanation: Cholinesterase inhibitors increase acetylcholine by preventing its breakdown. They have
indirect effects on other systems, but the primary direct action is on cholinergic transmission.
Q8. The mesolimbic pathway is involved in which functions? (Select all that apply)
A) Reward processing
B) Positive symptoms of schizophrenia
C) Motor coordination
D) Endocrine regulation
E) Addiction
Answer: A, B, E
Explanation: Mesolimbic (VTA to nucleus accumbens) mediates reward, addiction, and positive
symptoms (e.g., hallucinations, delusions) when hyperactive. Motor coordination is basal ganglia;
endocrine is tuberoinfundibular.
Q9. Which of the following are associated with reduced brain-derived neurotrophic factor (BDNF)
levels? (Select all that apply)
A) Major depression
B) Chronic stress
C) Antidepressant response
D) Hippocampal atrophy
E) Ketamine administration
Answer: A, B, D
Explanation: Depression and chronic stress lower BDNF, contributing to hippocampal atrophy.
Antidepressant response and ketamine increase BDNF (neurotrophic hypothesis).
Q10. Which statements about the default mode network (DMN) are correct? (Select all that apply)
, A) Active during mind-wandering and self-referential thought
B) Hyperactive in depression and anxiety
C) Deactivated during focused tasks
D) Involved in auditory processing
E) Abnormal in PTSD and schizophrenia
Answer: A, B, C, E
Explanation: DMN is active at rest, deactivated during tasks. Hyperactivity is seen in depression
(rumination), anxiety, PTSD, and schizophrenia (thought disorder). Auditory processing is primarily
temporal lobe.
Q11. Which genetic polymorphisms are associated with antipsychotic-induced weight gain? (Select all
that apply)
A) HTR2C (serotonin 2C receptor)
B) MC4R (melanocortin-4 receptor)
C) COMT Val158Met
D) SLC6A4 (serotonin transporter)
E) DRD2 Taq1A
Answer: A, B
Explanation: HTR2C and MC4R variants are consistently linked to antipsychotic-induced weight gain.
COMT and SLC6A4 are more linked to antipsychotic response and side effects (EPS, tardive dyskinesia)
rather than weight.
Q12. Which of the following are characteristic findings in hepatic encephalopathy? (Select all that
apply)
A) Asterixis (liver flap)
B) Elevated ammonia levels
C) Psychomotor slowing
D) Manic symptoms
E) EEG showing triphasic waves
Answer: A, B, C, E
Explanation: Hepatic encephalopathy presents with asterixis, elevated ammonia, cognitive slowing,
and triphasic waves on EEG. Manic symptoms are not typical; delirium or coma occurs in advanced
stages.
Q13. Which neuroimaging findings are associated with late-life depression? (Select all that apply)
A) White matter hyperintensities
B) Hippocampal atrophy
C) Increased prefrontal gray matter
