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

Studies published within the past decade that focus on fear extinction research. To highlight the disparity in research focused on women and female animals, we used keywords ‘fear extinction' and ‘male' or ‘female'.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Studies published within the past decade that focus on fear extinction research. To highlight the disparity in research focused on women and female animals, we used keywords ‘fear extinction' and ‘male' or ‘female'.

Mentions: We form associations between emotional events and co-occurring cues that can guide future behavioral outcomes. This is the basis of classical conditioning, a paradigm used to study mechanisms of associative learning and memory. In the past few decades, conditioned fear and its extinction have been the focus of extensive research efforts, in part, due to the clinical relevance of fear to the etiology and pathophysiology of many psychiatric disorders. Key nodes of brain regions involved in conditioned fear and fear extinction learning have been identified in rodents and humans.1 The majority of the rodent studies have been conducted in males and those conducted in humans, for the most part, disregard the role of sex differences in this form of learning (Figure 1). Below, we begin by outlining why this is an issue that deserves attention from a clinical perspective; a point previously alluded to by others.2 We review evidence for the relevance of fear extinction in studying anxiety disorders and then discuss the mechanisms by which estrogens might interact with the function of the fear extinction network. We conclude with a discussion of how natural variations, or exogenous manipulations, of estrogens throughout a woman's lifespan may translate to heightened vulnerability to psychopathology.


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

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

Studies published within the past decade that focus on fear extinction research. To highlight the disparity in research focused on women and female animals, we used keywords ‘fear extinction' and ‘male' or ‘female'.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Studies published within the past decade that focus on fear extinction research. To highlight the disparity in research focused on women and female animals, we used keywords ‘fear extinction' and ‘male' or ‘female'.
Mentions: We form associations between emotional events and co-occurring cues that can guide future behavioral outcomes. This is the basis of classical conditioning, a paradigm used to study mechanisms of associative learning and memory. In the past few decades, conditioned fear and its extinction have been the focus of extensive research efforts, in part, due to the clinical relevance of fear to the etiology and pathophysiology of many psychiatric disorders. Key nodes of brain regions involved in conditioned fear and fear extinction learning have been identified in rodents and humans.1 The majority of the rodent studies have been conducted in males and those conducted in humans, for the most part, disregard the role of sex differences in this form of learning (Figure 1). Below, we begin by outlining why this is an issue that deserves attention from a clinical perspective; a point previously alluded to by others.2 We review evidence for the relevance of fear extinction in studying anxiety disorders and then discuss the mechanisms by which estrogens might interact with the function of the fear extinction network. We conclude with a discussion of how natural variations, or exogenous manipulations, of estrogens throughout a woman's lifespan may translate to heightened vulnerability to psychopathology.

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