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By Sharleen Yuan Special Topics-Affective Disorders 10.2.09

ABERRANT FUNCTIONAL CONNECTIVITY OF DL PFC AND CINGULATE NETWORKS IN PATIENTS WITH MDD DURING WORKING MEMORY PROCESSING. By Sharleen Yuan Special Topics-Affective Disorders 10.2.09. Depression affects 5% of the total population. www.cdc.gov/nchs. Depression Symptoms (more than 2 weeks).

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By Sharleen Yuan Special Topics-Affective Disorders 10.2.09

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  1. ABERRANT FUNCTIONAL CONNECTIVITY OF DL PFC AND CINGULATE NETWORKS IN PATIENTS WITH MDD DURING WORKING MEMORY PROCESSING By Sharleen Yuan Special Topics-Affective Disorders 10.2.09

  2. Depression affects 5% of the total population www.cdc.gov/nchs

  3. Depression Symptoms (more than 2 weeks) • Agitation, restlessness, and irritability • Dramatic change in appetite, often with weight gain or loss • Extreme difficulty concentrating • Fatigue and lack of energy • Feelings of hopelessness and helplessness • Feelings of worthlessness, self-hate, and inappropriate guilt • Inactivity and withdrawal from usual activities, a loss of interest or pleasure in activities that were once enjoyed (such as sex) • Thoughts of death or suicide • Trouble sleeping or excessive sleeping

  4. “THE HOURS”

  5. Depression research has focused on monoamine transmission

  6. Different mechanisms and systems are now being examined • Genetics • BDNF • HPA axis • Stress • Structural changes • Abnormal brain activation • DLPFC activation (main focus)

  7. PFC anatomy and orientation Image: Caltech/Todd Hare

  8. ACC anatomy and orientation

  9. PFC: What does it do? • Weighs consequences of future actions • Plans and organizes those action • Integration of motor and sensory information • Executive functions • Planning and regulating behavior • Problem solver!

  10. PFC: What else does it do? • Concerned with sequencing of behavior over time • ST “working” memory • DLPFC: Densely interconnected association regions • Projects to numerous cortical and subcortical regions

  11. People with MDD had an increase in left DLPFC activation Matsuo, K. et al. (2007). Molecular Psychiatry, Vol 12.

  12. Depression and DLPFC • DLPFC-striatum-thalamus circuit and frontolimbic-subcoritcal circuit • Involved in control of cognitive and executive function (DLPFC primary center) • Debate b/twn hypoactivity and hyperactivity (more now showing hyperactivity)

  13. Depression and DLPFC • Hyperactivity of the DLPFC • Seen also in schizophrenia • Could be due to DA abnormalities • DA important in modulating prefrontal activation dur working memory • Underlie issue of abnormal function of frontolimbic network in frontolimbic circuit

  14. Depression and DLPFC • Why is there hyperactivity? • Could be a compensatory mechanism  increase WM-related activation is needed • But also found abnormalities in the ACC

  15. Depression and ACC • Anterior cingulate cortex • Contributes to executive functions • Attention, inhibition, cognitive conflicts • Key role in emotional expression, affect regulation, and cognitive processing • Significant activation in MDD

  16. Depression and ACC • Activated during low cognitive demand or neutral baseline • Is activation due to the cognitive task or reflect an aberrant TID? • Functional connectivity and relationship of lateral PFC and ACC not determined

  17. Hypothesis • In MDD patients: • Abberant functional connectivity pattern in DLPFC  increased TIA • Aberrant functional connectivity pattern in the ACC  decreased TID

  18. Methods • 8 males, 6 females with MDD • DSM-IV diagnosed w/o any other Axis I disorder • Pts treated w/ AD (different types) • Psychopathology rated through the BPRS, the HAMD-21, and the CGI • 7 males, 7 females in Control grp

  19. Methods

  20. H S G

  21. H S G

  22. r

  23. Results

  24. Results

  25. Results

  26. Discussion • Two main findings: • 1. connectivity abnormalities in the DLPF/parietal network ( + correlation w the delay period of WM task) • 2. connectivity abnormalities in the VLPF/cingulate network

  27. Discussion • Increased DLPFC suggests a compensatory recruitment • Increasing cognitive demand requires greater recruitment to maintain task performance

  28. Discussion • Increased ACC contributes to a failure of deactivation in MDD patients • MDD patients with more deactivation of ACC showed greater clinical improvement increased activation cld represent a neg prognostic regarding clinical recovery

  29. EPIC

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