Anxiety, Depression, Schizophrenia

stress

a physiological response to threat or challenge

anhedonia

inability to feel pleasure

chronic stress and HPA axis dysregulation linked to

hippocampal atrophy, increase in inflammatory cytokines, altered serotonin, norepinephrine neurotransmission

acute stress response (healthy)

adaptive, short term, beneficial

-increased cortisol, epinephrine, norepinephrine

-returns to baseline after stressor ends

chronic stress (pathologic)

harmful

-chronic HPA activation → cortisol remains elevated

-impaired negative feedback, cannot return to baseline

chronic stress leads to

issues with stress regulation, weakened immune function, metabolic changes, increased risk of anxiety/depression

anxiety

a state of preparation for danger characterized by arousal, vigilance, physiological preparedness, negative emotional states similar to fear

-disorder when persistent, excessive, or interferes with daily life

pathophysiology of anxiety

results from hyperresponsiveness of amygdala fear circuitry and reduction in cortical brain regions that normally suppress fear

common symptoms of anxiety

palpitations, sweating, shortness of breath, racing thoughts, avoidance, irritability

GABA neurotransmitter

GABA_A and GABA_B contribute to hyperpolarization

benzodiazepines

strengthens brain’s ability to inhibit GABA → more hyperpolarization → harder to reach action potential

depression

must last over 2 weeks and interfere with daily functioning; often occurs with other psychiatric disorders

-persistent sadness, anhedonia, and impaired functioning

symptoms of depression

single/recurrent episodes of depressed mood, anhedonia, feelings of worthlessness/guilt, decreased concentration, indecisiveness, sleep issues, possible suicidal ideation

major depressive disorder

-5 or more symptoms present during 2 week period, and must include either depressed mood or loss of interest/pleasure

depression risk factors (multifactional etiology)

increase vulnerability but DO NOT guarantee depression

-biological, environmental, physiological, physical illness, drugs

monoamine hypothesis (neurotransmitter hypothesis)

depression results from pathologically inadequate or dysregulated monoamine neurotransmission

serotonin (5-HT)

regulates mood, sleep, appetite

norepinephrine (NE)

energy, alertness, concentration

dopamine (DA)

pleasure, reward, motivation

imipramine

blocks presynaptic serotonin transporter → greater norepinephrine exposure

iproniazid

blocks MAO enzymes → reduces metabolic degradation of monoamines

reserpine

prevents packaging of monoamines into presynaptic vesicles

major neuronal circuitry of 5-HT in the CNS

brainstem raphe nuclei; serotonergic projections in CNS

NE in the CNS

locus ceruleus, amygdala, prefrontal cortex, ventral tegmental area

neurotrophic hypothesis

loss of neurotrophic support leads to depression

brain derived neurotrophic factor (BDNF)

help nerves and glia grow, survive, and stay healthy

depression treatment

combination of pharmacologic and nonpharmacologic

psychosis

symptom of a mental disorder characterized by a distorted perception of reality (delusions, hallucinations, disorganized thought)

schizophrenia

a chronic, debilitating disorder characterized by psychotic symptoms

-delusions, hallucinations, lack of motivation, social withdrawal, cognitive impairments, disconnection of thought & language

known causes of psychosis

medical disorders, psychiatric disorders, drug-induced (DA receptor agonists)

risk factors of schizophrenia

-genetic risk of schizophrenia and bipolar is highly polygenic

-environmental

positive symptoms of schizophrenia

presence of abnormal behaviors

-hallucinations, delusions, disorganized speech/thoughts/actions, catatonic behavior

negative symptoms of schizophrenia

absence of abnormal behaviors

-affective flattening, alogia (few words in speech), avolition (lack of motivation), anhedonia, asociality

cognitive symptoms of schizophrenia

deficit in attention, memory, organization/planning, learning

schizophrenia results from

imbalances in CNS neurotransmitters (excessive dopaminergic and serotonergic signaling)

glutamate hypothesis

low glutamate → problems with memory and perception

mesocortical signaling

associated with negative symptoms of schizophrenia, decreased D₁ receptors

mesolimbic signaling

associated with positive symptoms of schizophrenia, increased activation of D₂ receptors

1st generation antipsychotics (typical)

reduce positive symptoms, target dopamine

2nd generation antipsychotics (atypical)

help negative symptoms, target dopamine & serotonin