Mood Disorders

Question 1

Major depressive disorder (MDD)
- Characteristics (3)
- Prevalence

Answer 1

• Sadness
• Hopelessness
• Anhedonia
  —
• Diagnosed more in women
• Onset 27 years ild

Question 2

Major depressive disorder (MDD):
- Symptoms (9)
- DSM-5 diagnosis requirements

Answer 2

• Depressed mood
• Anhedonia
• Significant unintentional weight loss or gain
• Insomnia or hypersonbia
• Psychomotor changes (Agitation and slowing)
• Low energy, fatigue, tired ess
• Impaired ability to think, concentrate, make decisions
• Sense of worthlessness or excessive guilt
• Suicidal thoughts
  —
• Combo of 5+ symptoms during 2-week period; 1 symptom must be depressed mood or anhedonia
• Important not to have history of manic or hypomanic episodes cuz this would be bipolar disorder

Question 3

MDD risk factors (4)

Answer 3

• Early life trauma
• Recent major life stress
• Family history of depression (esp first-degree)
• Personal history of depression (Relapse)

Question 4

Areas of volumetric reductions in MDD (5)
- What circuit are some of these a part of?
- Gray matter is lower in what regions w/ early life trauma (CM+), family members (FH+), ppl w/ depression (MDD)

Answer 4

• Anterior cingulate cortex (ACC)
• Orbitofrontal cortex (OFC)
• Hippocampus
• Striatum
• Insula
• Cortico-striatal-pallidal-thalamic circuits (involved in cog and emotional processes)
  —
• CM+: Hippocampus and ACC
• FH+: Insula, cingulate cortex, OFC
• MDD: Hippocampus, insula, cingulate cortex, OFC

Question 5

Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) did diffusion tensor imaging (DTI) study
- Found changed in white matter where? (2)
- Diffs not present in who? Not related to what? What are they driven by?

Answer 5

• Corpus callosum
• Cingulum bundle
  —
• Not present in adolescents and first episode patients
• Not related to symptom severity
• Driven by recurrent MDD

Question 6

Metabolic activity in MDD:
- Increase where? (2)
- Decrease where? (1)

Answer 6

• Amygdala and OFC
• Increased emotional/threat response
  —
• Subgenual ACC
• Reduced reward processing

Question 7

Serotonin:
- Impacts what? (4)
- Reduced 5-HT receptor binding potential where? (3)
- This is a risk factor for what?
- Result of face matching task study w/ fearful/angry faces?

Answer 7

• Mood
• Response to stress
• Sleep-wake cycle
• Memory
  —
• Hippocampus
• Amygdala
• Raphe nuclei
  —
  Risk factor for developing MDD
  —
  Ppl w/ higher than avg amygdala reactions had lower 5HT1A receptor binding
• Shows receptor important for regulating responses to negative emotions

Question 8

MMD treatments:
- SSRI (Selective serotonin reuptake inhibitors); fluoxetine, paroxetine, sertraline
- Effect on symptoms
- Effects related to what changes (2)
- CBT (Cognitive behavioural therapy)
- Compared to medication?

Answer 8

SSRIs:
- Commonly prescribed antidepressants that increase lvls of serotonin in synapse by blocking serotonin transporter involved in reuptaking serotonin into neurons
- Little effect on cognitive symptoms but can increase serotonin within hours; takes 4-8 weeks to impact other symptoms tho
- Effects may be related to change in postsynaptic receptors or neurogenesis; Found in rodents that chronic treatment increased cells in hippocampus and hippocampal gray matter vol in humans after 8 weeks
—
CBT:
- Talk therapy w/ licensed therapist to reframe negative thinking + learn how to respond to challenging situations in more effective ways
- As effective as medicine for MDD and reduced relapse rates

Question 9

Bipolar disorder (BD):
- Age of onset
- Bipolar I disorder
- Bipolar II disorder
- Cyclothymic disorder (Cyclothymia)

Answer 9

• 25 years old
  —
  BIPOLAR I:
• 1+ manic episodes (no depression) lasting 1 week present most of the day nearly everyday
• At least 3 symptoms of mania (grandiosity, reduced need for sleep, increased talkativeness, flight of ideas, distractibility, increased activity/agitated movements, risky behavs)
• Mood disturbances must cause marked impairment in social/occupational function, necessitate hospitalization or have psychotic features
  —
  BIPOLAR II:
• 1+ hypomanic episode lasting at least 4 days, present most of the day, nearly every day
• Not severe enough to cause marked impairment, hospitalization, or psychotic features
• 1+ major depressive episode
  —
• At least 2 years, many periods of hypomanic and depressive symptoms but don’t meed criteria for episodes
• Symptoms lasted for at least 1/2 of time and never stopped for more than 2 months

Question 10

BD risk factors (4)

Answer 10

• Family history (w/ first-degree, 8-10 times more likely)
• Early life trauma (50% dealt with childhood abuse, leads to earlier onset and higher severity)
• Recent negative life events (Increases and lengthens depressive episode but not mania/hypomania)
• Recent goal attainment events (Increases manic/hypomanic but not depressive symptoms)

Question 11

Gray matter changes in BD (3)
White matter changes according to ENIGMA diffusion tensor imaging (DTI) study

Answer 11

Manic episodes assoc w/ decreased gray matter volume in:
- Dorsolateral PFC
- Inferior frontal cortex
- Anterior cingulate cortex (ACC)
*Euthymic periods had no structural or even increased changes, reflecting recovery mechanisms
—
- Corpus callosum
- Cingulum bundle

Question 12

BD treatments
- Lithium
- Anticonvulsants (Carbamazepine, divalproex (valproate), lamotrigine)
- Atypical antipsychotics (Risperidone, olanzapine, quetiapine)
- Antidepressants
- Cognitive behavioural therapy (CBT)

Answer 12

LITHIUM:
- Effective for treating mania/hypomania but slow and narrow therapeutic index; Modest effects for classic BD but increase risk of suicide
- Side effects: Nausea, decreased thyroid function, tremor, weight gain, impaired cognition, risk of toxicity
- Mechanisms still unknown but preserves/increases vol of brain structures involved in emotional regulation (PFC, hippocampus, amygdala), inhibits excitatory neurotransmission and increases GABA, targets second-messenger symptoms like protein kinase C (PKC) which is overexpressed in BD
—
ANTICONVULSANTS:
- Carbamezapine and divalproex used to treat mania (esp for mixed state and rapid cycling BD)
- Lamotrigine reduces risk of recurrent depressive eps, but not effective for mania
- Interferes w/ intracellular calcium signalling (blocks Ca2+ channels), agonistic fx on GABAergic neurotransmission (increase GABA receptors to increase release of GABA)
- Side effects: Nausea, dizziness, fatigue, skin rashes, weight gain
—
ANTIPSYCHOTICS:
- Efficacy in treating mania and mixed state BD; Modest effects for BD depression
- Side effects: Tardive dyskinesia, weight gain, diabetes, high cholesterol
—
ANTIDEPRESSANTS:
- Treats BD depression but efficacy and safety controversial
- May lead to mood switches and rapid cycling; requires combo w/ mood stabilizer to reduce risk
—
CBT:
- Treats BD depressuon
- Help identify and monitor early signs of mood changes, manage stress/interpersonal difficulties, encourage medication adherence, and develop/use relapse prevention plans

Question 13

Reward processing
- 3 broad components
- Reward system brain areas (6)

Answer 13

Encompasses response to rewarding stim, ability to learn from reward, anticipation of future rewards, engagement in goal-directed behavs towards rewards
- Drive toward a reward (motivation), hedonic exp (feelings of pleasure), reward learning (learn from and use rewards to guide behav)
—
- Ventral tegmental area (VTA)
- Ventral striatum (nucleus accumbens)
- Orbitofrontal cortex (OFC)
- Medial prefrontal cortex
- Anterior cingulate cortex (ACC)
- Anterior insula

Question 14

Reward processing:
- In MMD + reward learning task w/ mouth
- In BD + areas of higher activation (3)
- MMD vs BD rigged monetary reward task w/ cards

Answer 14

• Linked to reduced reward learning
• Task involved identifying if short or long mouth belonged to mouthless cartoon face and were given rigged rewards for correct answer (one mouth gave more rewards)
• MDD/high anhedonia showed reduced reward learning ability and didn’t show reward bias
  —
• Assoc w/ hyper-responsiveness to reward cues + reduced ability to delay responding for rewards even in euthymic state
• OFC, ventrolateral prefrontal cortex, ventral striatum
  —
• Guess whether card would be red or black + gain money if right; Rigged so equal wins and losses no matter what
• Wins>Losses would increase activity in ventromedial PFC, ACC, ventral striatum, insula (reward value and reward salience processing)
• Depression (MDD and BD) assoc w/ reduced activation of reward-related regions; BD depression assoc w/ greater activity in left ventral striatum compared to MDD