5 - Emotion dysregulation and MDD

How is emotion dysregulation defined

• extreme behavioural, emotional, cognitive dysfunctions

• Are unexpected in cultural context

• Associated with distress/impairment in functioning

Describe briefly the historical views on emotion dysregulation

• prehistoric/ancient ⇒ possession, supernatural

• Greco-Roman ⇒ imbalance of humour (4 fluids)

• Middle Ages ⇒ superstition

• Late 20th ⇒ interaction of biological/psychological factors

What are affective disorders?

• mood disorders

• Depressive disorders & bipolar disorders

Incidence vs prevalence

• Incidence = rate of new cases within a period (often rate of treatment as actual incidence of cases may be unknown)

• Prevalence = actual no of cases within a period

  • Period prevalence = measure of disease load

  • Lifetime prevalence = no of cases in total lifetime

  • Point prevalence = only active cases on specific date

MDD prevalence

• 300M globally

• ↑ in 18.4% from 2005~2015

• 12 months prevalence in US - 7%

• Age group diff - 18-29 3x ↑ than 60<

• Gender diff - f:m 1:1.5-3

MDD DSM5 diagnostic criteria

• 5 or more of 9, during 2 week period

• Core symptoms ⇒ mood, anhedonia

• Physiological symptoms ⇒ weight loss/gain & appetite change, insomnia/hypersomnia, psychomotor agitation, fatigue

• Cognitive symptoms ⇒ guilt/worthlessness, ↓ ability to think, thoughts of death

What is meant by relapse and remission?

• Relapse = return of disease/signs gayer period of improvement

• Remission = decrease/disappearance of signs/symptoms

• Persistence of depressive symptoms during remission is predictor for later relapse

What are the three confounding factors in MDD?

• first vs multiple episode

• Co-morbidity

• Medication

Briefly describe the development and course of MDD

• onset ↑ w puberty

• ↓ recovery relates related to psychotic features, anxiety, personality disorders, symptom severity

• As duration of remission ↑ risk of relapse ↓

Why is adolescence a critical period for the dev of MDD?

• Env & genetic risk ⇒ Abnormal brain derived neurotrophic factor (BDNF) expression, trigger onset of depression

• Activity-dependent growth factor, plays role in brain dev and neuroplasticity

  • Results in ↓ brain vol in PFC & hippocampus (susceptible to mood disorders)

• BDNF lvl peak in adolescence and ↓ w age

SUMMARY: Which brings regions show changes in GMV in MDD?

• ↓ Right anterior ACC (BA32)

  • regulation of negative emotion (negative mood reduction)

• ↓ Bilateral rostral & dorsal ACC

• ↓ Bilateral dm-frontal & right dl-frontal cortex

• ↑ Amygdala

SUMMARY: Which regions show an increase / decrease in activity for people with MDD?

Increase

• amygdala - emotion processing

• baseline pulvinar nucleus

• dACC

• pre CG

• S&M TG

• insula

Decrease

• dlPFC (left) - cog processing

• dorsal striatum

• caudate body

SUMMARY: Which regions show a decrease in activity in positive emotion processing for MDD?

• reward learning ⇒ right caudate nucleus, right thalamus

• reward processing ⇒ right caudate nucleus

• reward anticipation ⇒ right thalamus

MDD & regulation of negative emotion (Mak 2009)

• GMV in right anterior cingulate gyrus (BA 32) pos corr w negative mood reduction

• Dysfunctional ACC associated w ↓ ability to regulate/repress negative emotions

What happens to amygdala GMV in MDD w/wo medication (Hamilton et al). What does this show about the effects of antidepressants?

• No significant diff in amygdala volume btw depressed & never depressed - Accounted for by pos corr bw amygdala vol diff and proportion of medicated depressed people

• Studies w only unmedicated depressed ppl shows decrease in amygdala vol

• Antidepressants mediate ↑ in BDNF promoting neurogenesis + protecting against glucocorticoid toxicity in amygdala

What happens to GMV in ACC for MDD?

• ↓ in GMV encompassing bilateral rostral & dorsal ACC (BA 24, 32)

• Meta analysis of 23 studies

What happens to GMV in what region of the frontal cortex?

• GMV ↓ bilateral dorsal medial frontal cortex (BA 6/8/9) & right dorsal lateral frontal cortex (BA 9)

Amygdala & DLPFC activities in MDD

• ↓ left dlPFC (cognitive task) & ↑ amygdala (limbic - emotion processing) activity relate to depressed participants

• Decreased relationship bw amygdala & DLPFC in MDD ⇒ reduced regulation of amygdala by DLPFC

Activity in pulvinar nucleus (thalamus), amygdala

• ↑ activity in pulvinar nucleus for MDD

• When negative stimuli shown

  • ↑ response in amygdala, insula, dACC

  • ↓ response in dorsal striatum and dlPFC

    • (Striatum = receives glutamatergic/dopaminergic inputs. Divided to ventral (NAcc) dorsal (caudate nucleus & putamen). Involved in motor planning, DM, motivation, reward perception)

• Conclusion: ↑ baseline pulvinar activity potentiates response of salience network to neg stimuli

↑ baseline regional cerebral blood flow in the ______ nucleus for MDD > control

• pulvinar nucleus of thalamus

  • attention (anterior) & emotion (medial) processes. Integrates sensory info from different modalities

• Medial pulvinar nucleus - associated w binding emotional feature in WM representation

Brian responses to negative stimuli - meta analysis, Hamilton et al 2012

• MDD ⇒ ↑ amygdala, dACC, insula, middle & STG, pre central gyrus (Pre CG)

• Control ⇒ ↑ dlPFC, caudate body

What is the “neural functional model of depression”?

• high baseline pulvinar activity in MDD potentiates response of salience network to negative info

• Due to low striatal dopamine lvl → emotion info doesn’t travel up striatal-thalamic-cortical pathway to dlPFC

• No contextual processing/reappraisal

Which brain region shows reduced activation during reward processing, learning, and anticipation (positive emotion processing) in MDD?

This shows the critical role of what circuitry for emotion functions in MDD?

• reward learning ⇒ right caudate nucleus, right thalamus

• Reward processing ⇒ right caudate nucleus

• Reward anticipation ⇒ right thalamus

• PFC-striatal circuitry

What are the four psychopathological models of depression and their key theories?

• psychodynamic

  • childhood anger turn to self-hatred

  • Object-relations theory ⇒ depression caused by ill-formed representation of healthy relationships - struggles in forming/maintaining emotional contact

• Psychosocial/behavioural

  • Loss of s/o / Psychopathology in family

  • Learned helplessness, lack of perceived control

• Cognitive

• Biological

SUMMARY: What are some new concepts & key brain pathways/circuitries?

• BDNF: brain derived neurotropic factor

  • abnormal expression triggers onset of depression

• Relationship bw amygdala & dlPFC

  • low relationship indicates reduced regulation of amygdala by dlPFC

• Neural functional model of MDD

  • ↑ baseline activity in pulvinar nucleus (in thalamus) potentiates response of salience network to neg info

  • low striatal dopamine lvl → info doesn’t travel up striatal-thalamic-cortical pathway to dlPFC

  • no contextual processing/reappraisal