Limits...
Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

Cover KK, Maeng LY, Lebrón-Milad K, Milad MR - Transl Psychiatry (2014)

Bottom Line: Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear.Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction.In this review, we begin by highlighting the epidemiological differences in incidence rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.

ABSTRACT
Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders.

Show MeSH

Related in: MedlinePlus

Future directions for exploring the role of estradiol in fear extinction and psychopathology. An apparent correlation between fluctuating estradiol states and vulnerability for fear and anxiety disorders necessitates further research into where, how and when estradiol modulates the fear extinction network. Investigating these questions may provide new options for targeted, and thus more effective, treatment and therapy in the clinic. BDNF, brain-derived neurotrophic factor; MAPK, mitogen-activated protein kinase; mPFC, medial prefrontal cortex; PI3K, phosphoinositide 3-kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150242&req=5

fig6: Future directions for exploring the role of estradiol in fear extinction and psychopathology. An apparent correlation between fluctuating estradiol states and vulnerability for fear and anxiety disorders necessitates further research into where, how and when estradiol modulates the fear extinction network. Investigating these questions may provide new options for targeted, and thus more effective, treatment and therapy in the clinic. BDNF, brain-derived neurotrophic factor; MAPK, mitogen-activated protein kinase; mPFC, medial prefrontal cortex; PI3K, phosphoinositide 3-kinase.

Mentions: We have reviewed evidence that estradiol may influence the molecular and cellular machinery involved in fear extinction, a behavioral process that models the psychopathology of PTSD and anxiety disorders. Together, these data highlight the association between the dynamic estrogen states that occur across the female lifespan and increased vulnerability to anxiety-related disorders. It is imperative that future studies investigate fluctuations in levels of E2 to determine their possible associations with, and contributions to, vulnerability to mood and anxiety disorders in women. There are many questions that remain to be answered in this field that are related to where, how and when E2 modifies neural function to elicit its effects on extinction memory recall (Figure 6). Future research aimed at localizing and identifying cellular and molecular mechanisms by which estrogen modulates fear extinction and anxiety can better inform us of treatment targets and improve the efficacy of clinical applications.


Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

Cover KK, Maeng LY, Lebrón-Milad K, Milad MR - Transl Psychiatry (2014)

Future directions for exploring the role of estradiol in fear extinction and psychopathology. An apparent correlation between fluctuating estradiol states and vulnerability for fear and anxiety disorders necessitates further research into where, how and when estradiol modulates the fear extinction network. Investigating these questions may provide new options for targeted, and thus more effective, treatment and therapy in the clinic. BDNF, brain-derived neurotrophic factor; MAPK, mitogen-activated protein kinase; mPFC, medial prefrontal cortex; PI3K, phosphoinositide 3-kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150242&req=5

fig6: Future directions for exploring the role of estradiol in fear extinction and psychopathology. An apparent correlation between fluctuating estradiol states and vulnerability for fear and anxiety disorders necessitates further research into where, how and when estradiol modulates the fear extinction network. Investigating these questions may provide new options for targeted, and thus more effective, treatment and therapy in the clinic. BDNF, brain-derived neurotrophic factor; MAPK, mitogen-activated protein kinase; mPFC, medial prefrontal cortex; PI3K, phosphoinositide 3-kinase.
Mentions: We have reviewed evidence that estradiol may influence the molecular and cellular machinery involved in fear extinction, a behavioral process that models the psychopathology of PTSD and anxiety disorders. Together, these data highlight the association between the dynamic estrogen states that occur across the female lifespan and increased vulnerability to anxiety-related disorders. It is imperative that future studies investigate fluctuations in levels of E2 to determine their possible associations with, and contributions to, vulnerability to mood and anxiety disorders in women. There are many questions that remain to be answered in this field that are related to where, how and when E2 modifies neural function to elicit its effects on extinction memory recall (Figure 6). Future research aimed at localizing and identifying cellular and molecular mechanisms by which estrogen modulates fear extinction and anxiety can better inform us of treatment targets and improve the efficacy of clinical applications.

Bottom Line: Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear.Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction.In this review, we begin by highlighting the epidemiological differences in incidence rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.

ABSTRACT
Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders.

Show MeSH
Related in: MedlinePlus