본문 바로가기
KERD
논문KCI 등재

신경세포 신생과 패턴분리의 관점에서 본 우울증과 불안장애

Depression and Anxiety Disorder in Perspective of Neurogenesis and Pattern Separation

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류정신과학

초록

Major depressive disorder (MDD) and anxiety disorder (AD) are mental disorders with a high social burden. Since the discovery of neurogenesis, one effect of anti-depressant was revealed as increasing the neurogenesis of the dentate gyrus (DG). Thus, many researchers have speculated that neurogenesis may correlate with the pathogenesis of depression and anxiety disorders. It was reasonable to hypothesize that neurogenesis would be essential for the therapeutic mechanism. We call this new hypothesis the neurogenic theory. In this review, we investigated the validity and evidence of neurogenic theory through post-mortem studies and animal models. As a result, it seems to be a lack of strong evidence to claim that the defect of neurogenesis itself causes MDD and AD. However, neurogenesis seems to be essential, at least for improving depressive or anxiety behaviors. From the algorithmic perspective, we also discussed the pattern separation, suggested function of neurogenesis of the DG, in the relationship with the symptoms of mental disorder. We tried to show that it is appropriate to interpret the relationship between neurogenesis and mental disorder using the term “overgeneralization” rather than the theoretical term “pattern separation”. Overgeneralization was especially beneficial for interpreting the relationship between the defect of neurogenesis and post-traumatic stress syndrome (PTSD) among AD. It is necessary to further investigate the effect of neurogenesis in the treatment of mental illnesses such as MDD and AD including PTSD, and in the prognosis of patients.

Abstract

Major depressive disorder (MDD) and anxiety disorder (AD) are mental disorders with a high social burden. Since the discovery of neurogenesis, one effect of anti-depressant was revealed as increasing the neurogenesis of the dentate gyrus (DG). Thus, many researchers have speculated that neurogenesis may correlate with the pathogenesis of depression and anxiety disorders. It was reasonable to hypothesize that neurogenesis would be essential for the therapeutic mechanism. We call this new hypothesis the neurogenic theory. In this review, we investigated the validity and evidence of neurogenic theory through post-mortem studies and animal models. As a result, it seems to be a lack of strong evidence to claim that the defect of neurogenesis itself causes MDD and AD. However, neurogenesis seems to be essential, at least for improving depressive or anxiety behaviors. From the algorithmic perspective, we also discussed the pattern separation, suggested function of neurogenesis of the DG, in the relationship with the symptoms of mental disorder. We tried to show that it is appropriate to interpret the relationship between neurogenesis and mental disorder using the term “overgeneralization” rather than the theoretical term “pattern separation”. Overgeneralization was especially beneficial for interpreting the relationship between the defect of neurogenesis and post-traumatic stress syndrome (PTSD) among AD. It is necessary to further investigate the effect of neurogenesis in the treatment of mental illnesses such as MDD and AD including PTSD, and in the prognosis of patients.

참고문헌 (50)

  1. Drew MR, "Adult hippocampal neurogenesis as target for the treatment of depression", CNS Neurol Disord Drug Targets, 6, pp.205~218 (2007)
  2. Colucci-D’Amato L, "The end of the central dogma of neurobiology : stem cells and neurogenesis in adult CNS", Neurol Sci, 27, pp.266~270 (2006)
  3. Malberg JE, "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus", J Neurosci, 20, pp.9104~9110 (2000)
  4. Santarelli L, "Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants", Science, 301, pp.805~809 (2003)
  5. Kheirbek MA, "Neurogenesis and generalization : a new approach to stratify and treat anxiety disorders", Nat Neurosci, 15, pp.1613~1620 (2012)
  6. Marr D, "Simple memory : a theory for archicortex", Philos Trans R Soc Lond B Biol Sci, 262, pp.23~81 (1971)
  7. Yassa MA, "Pattern separation in the hippocampus", Trends Neurosci, 34, pp.515~525 (2011)
  8. Espósito MS, "Neuronal differentiation in the adult hippocampus recapitulates embryonic development", J Neurosci, 25, pp.10074~10086 (2005)
  9. Ge S, "GABA regulates synaptic integration of newly generated neurons in the adult brain", Nature, 439, pp.589~593 (2006)
  10. Toni N, "Neurons born in the adult dentate gyrus form functional synapses with target cells", Nat Neurosci, 11, pp.901~907 (2008)
  11. Lee H, "GABA mediates the network activity-dependent facilitation of axonal outgrowth from the newborn granule cells in the early postnatal rat hippocampus", Eur J Neurosci, 36, pp.2743~2752 (2012)
  12. Zhao C, "Mechanisms and functional implications of adult neurogenesis", Cell, 132, pp.645~660 (2008)
  13. Shors TJ, "Neurogenesis in the adult is involved in the formation of trace memories", Nature, 410, pp.372~376 (2001)
  14. Aimone JB, "Computational influence of adult neurogenesis on memory encoding", Neuron, 61, pp.187~202 (2009)
  15. Clelland CD, "A functional role for adult hippocampal neurogenesis in spatial pattern separation", Science, 325, pp.210~213 (2009)
  16. Sahay A, "Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation", Nature, 472, pp.466~470 (2011)
  17. Tronel S, "Adult-born neurons are necessary for extended contextual discrimination", Hippocampus, 22, pp.292~298 (2012)
  18. Aimone JB, "Modeling new neuron function : a history of using computational neuroscience to study adult neurogenesis", Eur J Neurosci, 33, pp.1160~1169 (2011)
  19. Becker S, "Neurogenesis and pattern separation : time for a divorce", Wiley Interdiscip Rev Cogn Sci, 8 (2017)
  20. Deisseroth K, "Excitation-neurogenesis coupling in adult neural stem", progenitor cells, 2004, pp.42, 535~552
  21. Saxe MD, "Paradoxical influence of hippocampal neurogenesis on working memory", Proc Natl Acad Sci U S A, 104, pp.4642~4646 (2007)
  22. Besnard A, "Adult hippocampal neurogenesis, fear generalization, and stress", Neuropsychopharmacology, 41, pp.24~44 (2015)
  23. Sumner JA, "Overgeneral autobiographical memory as a predictor of the course of depression : a meta-analysis", Behav Res Ther, 48, pp.614~625 (2010)
  24. van den Heuvel TJ, "An investigation of different aspects of overgeneralization in patients with major depressive disorder and borderline personality disorder", Brit J Clin Psychol, 51, pp.376~395 (2012)
  25. Shelton DJ, "A possible negative influence of depression on the ability to overcome memory interference", Behav Brain Res, 256, pp.20~26 (2013)
  26. Kitayama N, "Magnetic resonance imaging(MRI)measurement of hippocampal volume in posttraumatic stress disorder : A meta-analysis", J Affect Disorders, 88, pp.79~86 (2005)
  27. Wang Z, "Magnetic resonance imaging of hippocampal subfields in posttraumatic stress disorder", Arch Gen Psychiatry, 67, pp.296~303 (2010)
  28. Gilbertson MW, "Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma", Nat Neurosci, 5, pp.1242~1247 (2002)
  29. Gilbertson MW, "Configural cue performance in identical twins discordant for posttraumatic stress disorder : theoretical implications for the role of hippocampal function", Biol Psychiatry, 62, pp.513~520 (2007)
  30. Gilbertson MW, "Is trauma a causal agent of psychopathologic symptoms in posttraumatic stress disorder? Findings from identical twins discordant for combat exposure", J Clin Psychiatry, 71, pp.1324~1330 (2010)
  31. Kwak KP, "Role of Brain-Derived Neurotrophic Factor in depression", J Korean Soc Ther, 12, pp.112~120 (2005)
  32. Miller BR, "The current state of the neurogenic theory of depression and anxiety", Curr Opin Neurobiol, 30, pp.51~58 (2015)
  33. Sierra A, "Adult human neurogenesis : from microscopy to magnetic resonance imaging", Front Neurosci, 5, pp.47~ (2011)
  34. Reif A, "Neural stem cell proliferation is decreased in schizophrenia, but not in depression", Mol Psychiatr, 11, pp.514~522 (2006)
  35. Boldrini M, "Antidepressants increase neural progenitor cells in the human hippocampus", Neuropsychopharmacolgy, 34, pp.2376~2389 (2009)
  36. Lucassen PJ, "Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients", Neuropharmacology, 58, pp.940~949 (2010)
  37. Boldrini M, "Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression", Biol Psychiatry, 72, pp.562~571 (2012)
  38. Boldrini M, "Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression", Neuropsychopharmacology, 38, pp.1068~1077 (2013)
  39. Sorrells SF, "Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults", Nature, 555, pp.377~381 (2018)
  40. Boldrini M, "Human hippocampal neurogenesis persists throughout aging", Cell Stem Cell, 22, pp.589~599 (2018)
  41. Lydiatt WM, "Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer:randomized, double-blind, placebo-controlled clinical trial", JAMA Otolaryngol Head Neck Surg, 139, pp.678~686 (2013)
  42. Ruan L, "Neurogenesis in neurological and psychiatric diseases and brain injury : From bench to bedside", Prog Neurobiol, 115, pp.116~137 (2014)
  43. Valente MM, "α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress", Mol Pharmacol, 82, pp.271~280 (2012)
  44. Revest JM, "Adult hippocampal neurogenesis is involved in anxiety-related behaviors", Mol Psychiatry, 14, pp.959~967 (2009)
  45. Onksen JL, "Selective deletion of a cell cycle checkpoint kinase(ATR)reduces neurogenesis and alters responses in rodent models of behavioral affect", Neuropsychopharmacology, 36, pp.960~969 (2011)
  46. Petrik D, "The neurogenesis hypothesis of affective and anxiety disorders : Are we mistaking the scaffolding for the building", Neuropharmacology, 62, pp.21~34 (2012)
  47. Hill AS, "Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors", Neuropsychopharmacology, 40, pp.2368~2378 (2015)
  48. Anacker C, "Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus", Nature, 559, pp.98~102 (2018)
  49. Cascella NG, "Neurodevelopmental involvement in schizophrenia : the olfactory epithelium as an alternative model for research", J Neurochem, 102, pp.587~594 (2007)
  50. Manganas LN, "Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain", Science, 318, pp.980~985 (2007)

관련 논문AI추천

이 간행물의 다른 논문 (5건)