ANCC Psychiatric–Mental Health Nurse Practitioner Board Certification Final Examination 2026:
Integrative Neuropsychiatry, Advanced Psychopharmacokinetics, Medico-Legal Dilemmas, and
Evidence-Based Psychotherapy Synthesis
Questions 1–150 (Multiple Answers + Detailed Explanations)
Section 1: Integrative & Translational Neuroscience (Q1–20)
Q1. Which of the following statements about the role of the gut microbiome in psychiatric drug
metabolism are correct? (Select all that apply)
A) Gut bacteria can directly metabolize levodopa to dopamine
B) Eggerthella lenta reduces digoxin but not psychiatric drugs
C) Clostridium species metabolize risperidone to 9-hydroxyrisperidone
D) Microbial β-glucuronidases reactivate irinotecan (cancer drug) but also some psychotropics
E) Probiotics can alter blood levels of benzodiazepines
Answer: A, C, D, E
Explanation: Gut microbiota (Enterococcus faecalis) metabolize levodopa to dopamine, reducing
efficacy. Clostridium species convert risperidone. β-glucuronidases deconjugate drugs. Probiotic
Lactobacillus rhamnosus increases GABA and alters benzodiazepine metabolism in animal models.
Q2. Which statements about the glymphatic system and psychiatric disorders are correct? (Select all
that apply)
A) The glymphatic system clears waste products from the brain during sleep
B) Glymphatic dysfunction is implicated in Alzheimer's disease (beta-amyloid accumulation)
C) Chronic sleep deprivation impairs glymphatic clearance
D) Aquaporin-4 (AQP4) channels are essential for glymphatic flow
E) Glymphatic function is enhanced by norepinephrine during REM sleep
Answer: A, B, C, D
Explanation: Norepinephrine reduces glymphatic flow (REM sleep has low NE). Glymphatic is active
during NREM sleep. AQP4 genetic variants are linked to depression and TBI outcomes.
Q3. Which of the following are correct about the role of the periaqueductal gray (PAG) in anxiety and
panic? (Select all that apply)
A) Dorsolateral PAG is involved in panic-like responses
B) Ventrolateral PAG mediates passive coping and freezing
C) Deep brain stimulation (DBS) of the PAG is used for treatment-resistant panic disorder
, D) PAG activation is blocked by benzodiazepines
E) PAG is a target for novel panic treatments
Answer: A, B, C, D, E
Explanation: The PAG is a key panic circuit. DBS of PAG is experimental for panic disorder.
Benzodiazepines reduce PAG activation via GABA-A receptors.
Q4. Which of the following are correct about the role of the lateral habenula (LHb) in
depression? (Select all that apply)
A) LHb is hyperactive in depression models
B) LHb activity encodes negative reward prediction error
C) Deep brain stimulation of LHb is antidepressant in animal models
D) Ketamine may block LHb burst firing
E) LHb projects to the ventral tegmental area (VTA) and raphe
Answer: A, B, C, D, E
Explanation: The habenula is a "anti-reward" center. Hyperactivity drives anhedonia. Ketamine blocks
NMDA receptors on LHb neurons. DBS of LHb is experimental for TRD.
Q5. Which of the following are correct about the role of the immune system in catatonia? (Select all
that apply)
A) Anti-NMDA receptor encephalitis commonly presents with catatonia
B) Autoimmune catatonia responds to immunotherapy
C) Serum and CSF antibodies should be tested in new-onset catatonia
D) Corticosteroids are first-line for autoimmune catatonia
E) Catatonia is a core feature of anti-NMDA encephalitis (80-100%)
Answer: A, B, C, D, E
Explanation: Anti-NMDA encephalitis often presents with catatonia (mutism, posturing, rigidity) before
movement disorders. High-dose steroids, IVIG, plasmapheresis are used.
Q6. Which of the following are correct about the role of the inflammasome in suicide? (Select all that
apply)
A) NLRP3 inflammasome activation increases IL-1β and IL-18
B) Elevated IL-6 and TNF-α are found in suicide attempters
C) Postmortem brain of suicide victims shows microglial activation
D) Minocycline (inflammasome inhibitor) reduces suicidal ideation in some studies
E) Aspirin has been associated with lower suicide risk
Answer: A, B, C, D, E
Explanation: Inflammation is linked to suicide risk. Minocycline is being studied for suicide prevention.
Aspirin's anti-inflammatory effects may reduce risk.
,Q7. Which of the following are correct about the role of the transcobalamin (vitamin B12) system in
psychosis? (Select all that apply)
A) B12 deficiency causes psychosis, depression, and cognitive impairment
B) Homocysteine is elevated in B12 deficiency
C) Elevated homocysteine is a risk factor for treatment-resistant depression
D) Folate supplementation reduces homocysteine
E) Methylmalonic acid (MMA) is a more sensitive marker for B12 deficiency
Answer: A, B, C, D, E
Explanation: B12 deficiency is a reversible cause of psychosis. MMA is elevated in early B12 deficiency
before homocysteine rises.
Q8. Which statements about the role of the renin-angiotensin system (RAS) in the brain and
psychopathology are correct? (Select all that apply)
A) Brain RAS is independent of peripheral RAS
B) Angiotensin II (Ang II) contributes to stress responses
C) Angiotensin-converting enzyme (ACE) inhibitors have potential antidepressant effects
D) Angiotensin receptor blockers (ARBs) may reduce anxiety
E) CSF angiotensin II is elevated in treatment-resistant depression
Answer: A, B, C, D, E
Explanation: A central RAS exists. ACE inhibitors and ARBs are being repurposed for depression and
PTSD. Losartan reduces fear memory in animal models.
Q9. Which of the following are correct about the role of the purinergic system (ATP, adenosine) in
psychiatric disorders? (Select all that apply)
A) ATP acts as a neurotransmitter and neuromodulator
B) Adenosine A2A receptor antagonists (caffeine) have pro-anxiety effects
C) P2X7 receptor activation promotes inflammation and is linked to depression
D) P2X7 antagonists are being studied for mood disorders
E) Caffeine has mixed effects on anxiety (low dose anxiolytic, high dose anxiogenic)
Answer: A, B, C, D, E
Explanation: P2X7 is on microglia; activation releases IL-1β. P2X7 antagonists (e.g., JNJ-54175446) are
in clinical trials for depression.
Q10. Which of the following are correct about the role of the endocannabinoid system in fear
extinction? (Select all that apply)
A) Fear extinction is impaired in PTSD
B) Anandamide (AEA) facilitates fear extinction
C) Fatty acid amide hydrolase (FAAH) inhibition (e.g., PF-04457845) enhances extinction
, D) Cannabidiol (CBD) enhances fear extinction in healthy humans
E) THC impairs fear extinction
Answer: A, B, C, D, E
Explanation: All correct. FAAH inhibitors are being studied for PTSD. CBD is pro-extinction; THC is anti-
extinction.
Q11. Which of the following are correct about the role of the kynurenine pathway in bipolar
disorder? (Select all that apply)
A) Inflammation shifts tryptophan to kynurenine, away from serotonin
B) Quinolinic acid (QUIN) is elevated in bipolar depression
C) Kynurenic acid (KYNA) is elevated in mania (protective?)
D) QUIN is an NMDA agonist, neurotoxic
E) Kynurenine pathway metabolites predict treatment response
Answer: A, B, C, D, E
Explanation: Complex changes occur across mood states. QUIN is elevated in depression; KYNA may
be elevated in mania as a compensatory mechanism.
Q12. Which of the following are correct about the role of the microbiota-gut-brain axis in autism
spectrum disorder (ASD)? (Select all that apply)
A) ASD children have altered gut microbiota (reduced Bifidobacterium, Prevotella)
B) Microbial metabolites (short-chain fatty acids) affect behavior
C) Fecal microbiota transplantation (FMT) has shown benefit in open-label ASD studies
D) Probiotics have modest effects on gastrointestinal and behavioral symptoms
E) Microbiota-derived propionic acid is elevated in ASD
Answer: A, B, C, D, E
Explanation: Propionic acid (produced by Clostridia) is found in higher levels in ASD and induces ASD-
like behavior in rodents.
Q13. Which of the following are correct about the role of the orexin system in addiction? (Select all
that apply)
A) Orexin neurons in lateral hypothalamus are activated by drug cues
B) Orexin promotes drug-seeking behavior
C) Orexin antagonists reduce relapse in animal models
D) Suvorexant (orexin antagonist) is FDA-approved for insomnia
E) Orexin antagonists are being studied for alcohol use disorder
Answer: A, B, C, D, E
Explanation: Orexin is involved in reward seeking and relapse. Orexin antagonists are promising for
addiction.
Integrative Neuropsychiatry, Advanced Psychopharmacokinetics, Medico-Legal Dilemmas, and
Evidence-Based Psychotherapy Synthesis
Questions 1–150 (Multiple Answers + Detailed Explanations)
Section 1: Integrative & Translational Neuroscience (Q1–20)
Q1. Which of the following statements about the role of the gut microbiome in psychiatric drug
metabolism are correct? (Select all that apply)
A) Gut bacteria can directly metabolize levodopa to dopamine
B) Eggerthella lenta reduces digoxin but not psychiatric drugs
C) Clostridium species metabolize risperidone to 9-hydroxyrisperidone
D) Microbial β-glucuronidases reactivate irinotecan (cancer drug) but also some psychotropics
E) Probiotics can alter blood levels of benzodiazepines
Answer: A, C, D, E
Explanation: Gut microbiota (Enterococcus faecalis) metabolize levodopa to dopamine, reducing
efficacy. Clostridium species convert risperidone. β-glucuronidases deconjugate drugs. Probiotic
Lactobacillus rhamnosus increases GABA and alters benzodiazepine metabolism in animal models.
Q2. Which statements about the glymphatic system and psychiatric disorders are correct? (Select all
that apply)
A) The glymphatic system clears waste products from the brain during sleep
B) Glymphatic dysfunction is implicated in Alzheimer's disease (beta-amyloid accumulation)
C) Chronic sleep deprivation impairs glymphatic clearance
D) Aquaporin-4 (AQP4) channels are essential for glymphatic flow
E) Glymphatic function is enhanced by norepinephrine during REM sleep
Answer: A, B, C, D
Explanation: Norepinephrine reduces glymphatic flow (REM sleep has low NE). Glymphatic is active
during NREM sleep. AQP4 genetic variants are linked to depression and TBI outcomes.
Q3. Which of the following are correct about the role of the periaqueductal gray (PAG) in anxiety and
panic? (Select all that apply)
A) Dorsolateral PAG is involved in panic-like responses
B) Ventrolateral PAG mediates passive coping and freezing
C) Deep brain stimulation (DBS) of the PAG is used for treatment-resistant panic disorder
, D) PAG activation is blocked by benzodiazepines
E) PAG is a target for novel panic treatments
Answer: A, B, C, D, E
Explanation: The PAG is a key panic circuit. DBS of PAG is experimental for panic disorder.
Benzodiazepines reduce PAG activation via GABA-A receptors.
Q4. Which of the following are correct about the role of the lateral habenula (LHb) in
depression? (Select all that apply)
A) LHb is hyperactive in depression models
B) LHb activity encodes negative reward prediction error
C) Deep brain stimulation of LHb is antidepressant in animal models
D) Ketamine may block LHb burst firing
E) LHb projects to the ventral tegmental area (VTA) and raphe
Answer: A, B, C, D, E
Explanation: The habenula is a "anti-reward" center. Hyperactivity drives anhedonia. Ketamine blocks
NMDA receptors on LHb neurons. DBS of LHb is experimental for TRD.
Q5. Which of the following are correct about the role of the immune system in catatonia? (Select all
that apply)
A) Anti-NMDA receptor encephalitis commonly presents with catatonia
B) Autoimmune catatonia responds to immunotherapy
C) Serum and CSF antibodies should be tested in new-onset catatonia
D) Corticosteroids are first-line for autoimmune catatonia
E) Catatonia is a core feature of anti-NMDA encephalitis (80-100%)
Answer: A, B, C, D, E
Explanation: Anti-NMDA encephalitis often presents with catatonia (mutism, posturing, rigidity) before
movement disorders. High-dose steroids, IVIG, plasmapheresis are used.
Q6. Which of the following are correct about the role of the inflammasome in suicide? (Select all that
apply)
A) NLRP3 inflammasome activation increases IL-1β and IL-18
B) Elevated IL-6 and TNF-α are found in suicide attempters
C) Postmortem brain of suicide victims shows microglial activation
D) Minocycline (inflammasome inhibitor) reduces suicidal ideation in some studies
E) Aspirin has been associated with lower suicide risk
Answer: A, B, C, D, E
Explanation: Inflammation is linked to suicide risk. Minocycline is being studied for suicide prevention.
Aspirin's anti-inflammatory effects may reduce risk.
,Q7. Which of the following are correct about the role of the transcobalamin (vitamin B12) system in
psychosis? (Select all that apply)
A) B12 deficiency causes psychosis, depression, and cognitive impairment
B) Homocysteine is elevated in B12 deficiency
C) Elevated homocysteine is a risk factor for treatment-resistant depression
D) Folate supplementation reduces homocysteine
E) Methylmalonic acid (MMA) is a more sensitive marker for B12 deficiency
Answer: A, B, C, D, E
Explanation: B12 deficiency is a reversible cause of psychosis. MMA is elevated in early B12 deficiency
before homocysteine rises.
Q8. Which statements about the role of the renin-angiotensin system (RAS) in the brain and
psychopathology are correct? (Select all that apply)
A) Brain RAS is independent of peripheral RAS
B) Angiotensin II (Ang II) contributes to stress responses
C) Angiotensin-converting enzyme (ACE) inhibitors have potential antidepressant effects
D) Angiotensin receptor blockers (ARBs) may reduce anxiety
E) CSF angiotensin II is elevated in treatment-resistant depression
Answer: A, B, C, D, E
Explanation: A central RAS exists. ACE inhibitors and ARBs are being repurposed for depression and
PTSD. Losartan reduces fear memory in animal models.
Q9. Which of the following are correct about the role of the purinergic system (ATP, adenosine) in
psychiatric disorders? (Select all that apply)
A) ATP acts as a neurotransmitter and neuromodulator
B) Adenosine A2A receptor antagonists (caffeine) have pro-anxiety effects
C) P2X7 receptor activation promotes inflammation and is linked to depression
D) P2X7 antagonists are being studied for mood disorders
E) Caffeine has mixed effects on anxiety (low dose anxiolytic, high dose anxiogenic)
Answer: A, B, C, D, E
Explanation: P2X7 is on microglia; activation releases IL-1β. P2X7 antagonists (e.g., JNJ-54175446) are
in clinical trials for depression.
Q10. Which of the following are correct about the role of the endocannabinoid system in fear
extinction? (Select all that apply)
A) Fear extinction is impaired in PTSD
B) Anandamide (AEA) facilitates fear extinction
C) Fatty acid amide hydrolase (FAAH) inhibition (e.g., PF-04457845) enhances extinction
, D) Cannabidiol (CBD) enhances fear extinction in healthy humans
E) THC impairs fear extinction
Answer: A, B, C, D, E
Explanation: All correct. FAAH inhibitors are being studied for PTSD. CBD is pro-extinction; THC is anti-
extinction.
Q11. Which of the following are correct about the role of the kynurenine pathway in bipolar
disorder? (Select all that apply)
A) Inflammation shifts tryptophan to kynurenine, away from serotonin
B) Quinolinic acid (QUIN) is elevated in bipolar depression
C) Kynurenic acid (KYNA) is elevated in mania (protective?)
D) QUIN is an NMDA agonist, neurotoxic
E) Kynurenine pathway metabolites predict treatment response
Answer: A, B, C, D, E
Explanation: Complex changes occur across mood states. QUIN is elevated in depression; KYNA may
be elevated in mania as a compensatory mechanism.
Q12. Which of the following are correct about the role of the microbiota-gut-brain axis in autism
spectrum disorder (ASD)? (Select all that apply)
A) ASD children have altered gut microbiota (reduced Bifidobacterium, Prevotella)
B) Microbial metabolites (short-chain fatty acids) affect behavior
C) Fecal microbiota transplantation (FMT) has shown benefit in open-label ASD studies
D) Probiotics have modest effects on gastrointestinal and behavioral symptoms
E) Microbiota-derived propionic acid is elevated in ASD
Answer: A, B, C, D, E
Explanation: Propionic acid (produced by Clostridia) is found in higher levels in ASD and induces ASD-
like behavior in rodents.
Q13. Which of the following are correct about the role of the orexin system in addiction? (Select all
that apply)
A) Orexin neurons in lateral hypothalamus are activated by drug cues
B) Orexin promotes drug-seeking behavior
C) Orexin antagonists reduce relapse in animal models
D) Suvorexant (orexin antagonist) is FDA-approved for insomnia
E) Orexin antagonists are being studied for alcohol use disorder
Answer: A, B, C, D, E
Explanation: Orexin is involved in reward seeking and relapse. Orexin antagonists are promising for
addiction.
