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Questions and Answers
A patient presents with hypertension, tachycardia, myoclonic jerking, and agitation a few hours after starting a new medication. Which condition is most likely?
A patient presents with hypertension, tachycardia, myoclonic jerking, and agitation a few hours after starting a new medication. Which condition is most likely?
- Acute Dystonic Reaction
- Serotonin Syndrome (correct)
- Tardive Dyskinesia
- Neuroleptic Malignant Syndrome
Which genetic abnormality is most likely associated with the development of schizophrenia?
Which genetic abnormality is most likely associated with the development of schizophrenia?
- GRIN2A deletion (correct)
- Trisomy 21
- Fragile X syndrome
- Huntington's disease
Which of the following environmental factors is most strongly associated with an increased risk of developing schizophrenia?
Which of the following environmental factors is most strongly associated with an increased risk of developing schizophrenia?
- Relocation to a new geographic region in adulthood
- History of childhood trauma or abuse (correct)
- Regular consumption of a high-sugar diet
- Advanced education
A patient with schizophrenia is experiencing auditory hallucinations and paranoia. Which of the following pathophysiological mechanisms is most likely responsible for these symptoms?
A patient with schizophrenia is experiencing auditory hallucinations and paranoia. Which of the following pathophysiological mechanisms is most likely responsible for these symptoms?
Which symptom is considered a negative symptom of schizophrenia?
Which symptom is considered a negative symptom of schizophrenia?
A patient with schizophrenia exhibits a decreased ability to plan and make rational decisions. Which category of symptoms does this fall under?
A patient with schizophrenia exhibits a decreased ability to plan and make rational decisions. Which category of symptoms does this fall under?
Before diagnosing a patient with schizophrenia, it is MOST important to rule out other potential causes of psychosis/altered mental status, such as:
Before diagnosing a patient with schizophrenia, it is MOST important to rule out other potential causes of psychosis/altered mental status, such as:
Which medication is considered a first-generation antipsychotic?
Which medication is considered a first-generation antipsychotic?
Why is it important to avoid prescribing first-generation antipsychotics as first-line agents?
Why is it important to avoid prescribing first-generation antipsychotics as first-line agents?
Which of the following is a critical monitoring parameter for patients taking clozapine?
Which of the following is a critical monitoring parameter for patients taking clozapine?
Which of the following is NOT a primary mechanism contributing to norepinephrine (NE) deficiency?
Which of the following is NOT a primary mechanism contributing to norepinephrine (NE) deficiency?
What is the most likely consequence of increased norepinephrine (NE) activity within the amygdala?
What is the most likely consequence of increased norepinephrine (NE) activity within the amygdala?
A patient exhibits decreased goal-motivated behavior, anhedonia, and difficulty finding emotional events meaningful. Which neurotransmitter deficiency is MOST likely contributing to these symptoms?
A patient exhibits decreased goal-motivated behavior, anhedonia, and difficulty finding emotional events meaningful. Which neurotransmitter deficiency is MOST likely contributing to these symptoms?
Which brain region is NOT directly associated with D2 receptor activity related to emotional processing?
Which brain region is NOT directly associated with D2 receptor activity related to emotional processing?
Which of the following is NOT a recognized function of brain-derived neurotrophic factor (BDNF)?
Which of the following is NOT a recognized function of brain-derived neurotrophic factor (BDNF)?
A patient presents with symptoms of depression. Which of the following biochemical imbalances is LEAST likely to contribute to their condition?
A patient presents with symptoms of depression. Which of the following biochemical imbalances is LEAST likely to contribute to their condition?
Atrophy of the prefrontal cortex due to BDNF deficiency would most likely result in:
Atrophy of the prefrontal cortex due to BDNF deficiency would most likely result in:
Damage to which brain area would MOST directly impair a person's ability to form new emotional memories associated with specific events?
Damage to which brain area would MOST directly impair a person's ability to form new emotional memories associated with specific events?
A researcher is investigating therapeutic targets for depression. Stimulating which serotonergic receptor in the emotional centers of the brain would likely have the MOST beneficial effect?
A researcher is investigating therapeutic targets for depression. Stimulating which serotonergic receptor in the emotional centers of the brain would likely have the MOST beneficial effect?
According to the SIGECAPS criteria, which of the following would NOT be considered a typical symptom of major depressive disorder?
According to the SIGECAPS criteria, which of the following would NOT be considered a typical symptom of major depressive disorder?
A patient presents with depressive symptoms that began approximately one month after giving birth. Which of the following conditions is MOST likely?
A patient presents with depressive symptoms that began approximately one month after giving birth. Which of the following conditions is MOST likely?
Which scenario would MOST likely lead to decreased serotonin production in the brain?
Which scenario would MOST likely lead to decreased serotonin production in the brain?
A patient with seasonal affective disorder (SAD) is being treated with light therapy. What is the intended mechanism of action related to serotonin activity?
A patient with seasonal affective disorder (SAD) is being treated with light therapy. What is the intended mechanism of action related to serotonin activity?
Which of the following antidepressants is also commonly indicated for smoking cessation?
Which of the following antidepressants is also commonly indicated for smoking cessation?
A male patient taking trazodone reports experiencing a painful erection lasting longer than four hours. What is the MOST appropriate course of action?
A male patient taking trazodone reports experiencing a painful erection lasting longer than four hours. What is the MOST appropriate course of action?
Chronic stress and PTSD can lead to Brain-Derived Neurotrophic Factor (BDNF) deficiency. What is the MOST likely consequence of reduced BDNF levels in areas of the brain important for mood regulation?
Chronic stress and PTSD can lead to Brain-Derived Neurotrophic Factor (BDNF) deficiency. What is the MOST likely consequence of reduced BDNF levels in areas of the brain important for mood regulation?
A new drug aims to treat depression by targeting the hypothalamic-pituitary-adrenal (HPA) axis. What would be the expected outcome of a successful drug?
A new drug aims to treat depression by targeting the hypothalamic-pituitary-adrenal (HPA) axis. What would be the expected outcome of a successful drug?
A patient's depression is linked to chronic inflammation. How does inflammation contribute to reduced serotonin levels?
A patient's depression is linked to chronic inflammation. How does inflammation contribute to reduced serotonin levels?
A researcher discovers a compound that selectively inhibits the 5-HT2A receptor in the emotional centers of the brain. What is the MOST likely antidepressant effect of this compound?
A researcher discovers a compound that selectively inhibits the 5-HT2A receptor in the emotional centers of the brain. What is the MOST likely antidepressant effect of this compound?
If a person is having trouble making rational decisions, and lacks goal-motivated behavior, which area of their brain is MOST likely to be impaired?
If a person is having trouble making rational decisions, and lacks goal-motivated behavior, which area of their brain is MOST likely to be impaired?
Flashcards
Monoamine Deficiency in Depression
Monoamine Deficiency in Depression
Deficiencies in serotonin (5-HT), norepinephrine (NE), and dopamine (DA).
Cortisol's Role in Depression
Cortisol's Role in Depression
Excessive cortisol release leading to neurotoxicity in the CNS.
Hyperinflammation in the CNS
Hyperinflammation in the CNS
Increased pro-inflammatory cytokines and microglial cell activation, causing neuronal damage.
Brain Centers & Depression
Brain Centers & Depression
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5-HT1A (post-synaptic) Receptor
5-HT1A (post-synaptic) Receptor
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5-HT1A (pre-synaptic) & 5-HT2A Receptor
5-HT1A (pre-synaptic) & 5-HT2A Receptor
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Serotonin Deficiency Causes
Serotonin Deficiency Causes
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Tryptophan Deficiency
Tryptophan Deficiency
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Decreased Serotonin Release
Decreased Serotonin Release
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Chronic Inflammation Effects
Chronic Inflammation Effects
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Locus Coeruleus
Locus Coeruleus
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Causes of NE Deficiency
Causes of NE Deficiency
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Causes of NE Excess
Causes of NE Excess
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Increased NE Effects in Emotional Centers
Increased NE Effects in Emotional Centers
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Consequences of DA Deficiency
Consequences of DA Deficiency
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DA Receptors in Emotional Centers
DA Receptors in Emotional Centers
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Normal BDNF Functions
Normal BDNF Functions
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Consequences of BDNF Deficiency
Consequences of BDNF Deficiency
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SSRI Mechanism of Action
SSRI Mechanism of Action
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SNRI Mechanism
SNRI Mechanism
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Serotonin Syndrome
Serotonin Syndrome
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Schizophrenia: Genetic Risk
Schizophrenia: Genetic Risk
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Schizophrenia: Environmental Risks
Schizophrenia: Environmental Risks
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Schizophrenia: Positive Symptoms
Schizophrenia: Positive Symptoms
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Schizophrenia: Positive Symptoms Cause
Schizophrenia: Positive Symptoms Cause
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Schizophrenia: Negative Symptoms
Schizophrenia: Negative Symptoms
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Schizophrenia: Negative Symptoms Cause
Schizophrenia: Negative Symptoms Cause
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Schizophrenia: Cognitive Symptoms
Schizophrenia: Cognitive Symptoms
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Schizophrenia: Rule Outs
Schizophrenia: Rule Outs
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Clozapine Indications
Clozapine Indications
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Study Notes
Biochemical Basis of Depression
- Monoamine Deficiency: Decreases in serotonin (5-HT), norepinephrine (NE), and dopamine (DA)
- Excessive Upregulation of Cortisol Release: HPA Axis dysfunction, Cushing Disease/Syndrome; cortisol is neurotoxic in the CNS
- Hyperinflammation within the CNS: Increased pro-inflammatory cytokines, microglial cell activation, neuronal destruction
- Brain-Derived Neurotrophic Factor (BDNF) Deficiency: Secondary to chronic stress or PTSD
- Structural Damage to Brain: Hippocampal damage, prefrontal cortex damage
Brain Centers Involved with Depression
- Prefrontal Cortex: Rational decision making, goal-motivated behavior
- Amygdala: Fear, aggression
- Hippocampus: Memory (learning, cognition), emotional attachment to memories
- Ventral Tegmental Area (VTA), Nucleus Accumbens: Reward/Pleasure Centers
Serotonergic Receptors in Emotional Centers
- 5-HT1A Post-synaptic Receptor: Stimulatory, promotes emotional stability, rational decision making, and establishes emotional memory
- 5-HT1A Pre-synaptic Receptor: Autoreceptor, re-uptakes serotonin, resulting in decreased serotonergic activity
- 5-HT2A Receptor: Inhibitory, decreases serotonergic activity
Causes of Serotonin Deficiency
- Tryptophan Deficiency: Precursor to serotonin
- Increased Inflammation: Tryptophan shunted into biochemical pathways promoting microglial cell activation
- Decreased Serotonin Release: Decreased melatonin secretion from the pineal gland, leading to decreased serotonin release from the brainstem, which is a mechanism for seasonal depression
- Increased Activity of 5-HT Receptors: Increased presynaptic 5-HT1A, 5-HT2A receptor activity, which downregulates serotonergic activity
- Chronic Inflammation: Increases microglial cell activity and pro-inflammatory cytokine expression, leading to neurotoxicity and decreased available tryptophan for serotonin production
Norepinephrine (NE) Production and Deficiency
- NE Production: Locus Coeruleus in the brainstem is the primary center
- Causes of NE Deficiency:
- Destruction/Dysfunction of the Brainstem (Locus Coeruleus): Brainstem strokes, malignancy
- Decreased Expression of Adrenergic Receptors: Primarily α1
- Increased NET Expression: Increased NE reuptake from the synaptic cleft
Norepinephrine (NE) Excess
- Causes of NE Excess: Hyperinflammation, sleep deprivation
- Pathophysiologic Effects in Emotional Centers:
- Amygdala: Increased fear and aggression to small stimuli
- Hippocampus: Excessive upregulation of fight or flight response to traumatic memories
Dopamine (DA) Deficiency
- Consequences:
- Decreased goal-motivated behavior, decreased response to rewarding stimuli
- Anhedonia (lack of pleasure)
- Decreased attachment of abstract/philosophical meaning to emotional events
- Receptors Involved in DA Physiology:
- D1 Receptors: Located in the prefrontal cortex and amygdala
- D2 Receptors: Located in the hippocampus and amygdala
Brain-Derived Neurotrophic Factor (BDNF)
- Normal Physiologic Functions:
- Neurogenesis
- Neuroplasticity: Creation of synaptic connections, strengthening response to stimuli (critical in learning, emotional memory)
- Decreased Inflammation, decreased oxidative stress
- Consequences of Deficiency:
- Hippocampal Atrophy: Impairments in memory formation
- Prefrontal Cortex Atrophy: Impairments in rational decision making
- Amygdala Hyperreactivity: Increased fear, aggression
- Decreased Neuroplasticity: Decreased cognition, learning
- BDNF autonomously responds in response to antidepressant pharmacotherapy and positive response to therapy
SIGECAPS Criteria for Depression
- Sleeplessness
- Loss of interest, anhedonia, sexual urges/impotence
- Guilt, feeling worthless
- Decreased energy, fatigue
- Decreased concentration, motivation to learn
- Appetite changes (usually decreased, but can be increased)
- Psychomotor agitations (restlessness, racing thoughts, fidgeting, irritability)
- Suicidal Ideation (thoughts, plans)
Important Definitions of Depression
- Major Depressive Disorder: At least 5 SIGECAPS symptoms for 2 consecutive weeks; not due to medical causes, no mania
- Atypical Depression: Depressive phenotypes not meeting MDD criteria
- Postpartum Depression: At least 5 SIGECAPS symptoms after delivery for 2 weeks; can occur up to 1 year after delivery
- Schizoaffective Disorder: Depressive phenotypes (not necessarily 5 SIGECAPS) + schizophrenia
- Seasonal Depression: Depressive symptoms at a particular time of year (usually winter), improving after the season; decreased sunlight affects melatonin secretion and serotonin release
Pharmacologic Interventions for Depression
- SSRIs (Selective Serotonin Reuptake Inhibitors)
- First Line
- Inhibit 5-HT1A presynaptic and 5-HT2A receptors, increasing synaptic serotonin
- Examples: Sertraline, Fluoxetine, Citalopram, Escitalopram
- SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
- Increase serotonin and NE availability
- Examples: Venlafaxine, Duloxetine
- DNRIs (Dopamine-Norepinephrine Reuptake Inhibitors)
- Increase DA and NE availability
- Bupropion: Indicated for smoking cessation; Black Box Warning: Lowers seizure threshold, increasing seizure risk
- Tricyclic Antidepressants
- Reserved for treatment-resistant depression due to side effects (cardiotoxicity)
- Function as SNRIs
- Amitriptyline is most commonly used
- MAOIs (Monoamine Oxidase Inhibitors)
- Patients must avoid tyramine-containing foods to prevent "tyramine pressor response," causing severe hypertension and stroke risk
- Examples: Selegiline (MAO-B inhibitor), Phenelzine (MAO-B, MAO-A inhibitor)
- Special Antidepressants:
- Mirtazepine: SNRI, enhances DA release in the nucleus accumbens; used for patients needing weight gain
- Trazodone: Serotonin receptor antagonist (5-HT1A presynaptic), NE receptor antagonist (in amygdala), H1 receptor antagonist (promotes sleep); good for insomnia; Side effect: Priapism (erections > 4 hours require ER visit)
Serotonin Syndrome
- Hyperstimulation of serotonergic receptors leads to:
- Autonomic Instability: Hypertension, tachycardia, diaphoresis
- Neuromuscular Hyperreactivity: Myoclonic jerking, hyperreflexia
- Acutely Altered Mental Status: Agitation, confusion, coma
- Symptoms occur within hours
- Management:
- ABCs (airway, breathing, circulation)
- IV Benzodiazepines (Lorazepam, Midazolam preferred)
- IV Fluids, cooling blanket
Schizophrenia
- Genetic Abnormality: GRIN2A deletion (encodes NMDA glutamatergic receptors); absence decreases glutamate effect, increasing DA and promoting positive symptoms
- Environmental Factors: Childhood trauma/abuse, cannabis abuse (especially in teenage years), imprisonment
- Positive Symptoms: Hallucinations, delusions, paranoia, abnormal motor behavior, disorganized thinking/speech; caused by dopamine hyperactivity
- Negative Symptoms: Apathy/reduced emotional affect, lack of motivation, anhedonia, social withdrawal; caused by decreased serotonergic, NE, and DA function
- Cognitive Symptoms: Impaired rational thinking, memory issues, attention deficit, distortions in perspectives
- Schizophrenia is a diagnosis of exclusion: Rule out infections, electrolyte abnormalities, other psychiatric disorders (Bipolar I disorder, MDD), drug-induced psychosis
- Pharmacologic Management:
- First Generation Antipsychotics: Haloperidol, Fluphenazine, Chlorpromazine; large side effect profiles, but useful for non-compliant patients due to IM availability
- Second Generation Antipsychotics: Risperidone, Olanzapine, Quetiapine, Aripiprazole, Clozapine; first line once diagnosis is consolidated; decreased cardiotoxicity risk (though still possible), increased risk of metabolic syndromes
- Clozapine: Useful in treatment-resistant schizophrenia; monitor for AGRANULOCYTOSIS
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Description
Questions covering schizophrenia including symptoms and diagnosis. Also covers environmental factors, pathophysiology, and medications. First-generation antipsychotics are also discussed.
