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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.

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Sex differences in the lifetime incidence of psychiatric disorders vary from higher incidence in women, to no differences, to higher in men. Women/men lifetime incidence ratio was obtained directly from the publications referenced within the table or were calculated from the percentages of lifetime incidence published in the referenced studies. Superscripted letters next to each ratio reflects the citation from which we obtained such data: a, ref. 18; b, ref. 19; c, ref. 20; d, ref. 21; e, 22; f, ref. 23; g, ref. 24; h, ref. 25; i, ref. 26. *Of note, a sex bias for OCD is under debate and may depend on age; one study reports greater incidence among boys than girls. ADHD, attention deficit hyperactivity disorder; OCD, obsessive compulsive disorder; PTSD, posttraumatic stress disorder.27
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fig2: Sex differences in the lifetime incidence of psychiatric disorders vary from higher incidence in women, to no differences, to higher in men. Women/men lifetime incidence ratio was obtained directly from the publications referenced within the table or were calculated from the percentages of lifetime incidence published in the referenced studies. Superscripted letters next to each ratio reflects the citation from which we obtained such data: a, ref. 18; b, ref. 19; c, ref. 20; d, ref. 21; e, 22; f, ref. 23; g, ref. 24; h, ref. 25; i, ref. 26. *Of note, a sex bias for OCD is under debate and may depend on age; one study reports greater incidence among boys than girls. ADHD, attention deficit hyperactivity disorder; OCD, obsessive compulsive disorder; PTSD, posttraumatic stress disorder.27

Mentions: Epidemiological studies highlight significant differences between men and women in the incidence of psychiatric disorders (Figure 2). There is a higher incidence in men for autism, attention deficit hyperactivity disorder, schizophrenia and Parkinson's disease. Conversely, women are more susceptible to depression, anxiety and posttraumatic stress disorder (PTSD). In addition to differences in incidence, many psychiatric disorders are characterized by marked sex differences in progression and severity. Women are twice as likely to be diagnosed with PTSD;3, 4, 5, 6 have longer symptom duration,7 higher symptom severity and functional impairment,8 and have worse quality of life.9 Women with obsessive compulsive disorder are more likely to have more contamination/cleaning obsessions10 and their symptoms begin or worsen at menarche and postpartum.11 Women comprise 60% of individuals with generalized anxiety disorder and are more likely to develop comorbid psychiatric disorders and have worse prognosis and impairment.12,13 In addition to increased incidence of panic disorder in women, studies also suggest that panic attacks occur more frequently in women relative to men.14,15 Data indicate that women are at higher risk of developing anxiety disorders during reproductive life events such as menarche, menstruation, pregnancy, parturition and menopause.16,17 All together, these epidemiological data suggest that gonadal hormones may have a role in the onset of psychiatric disorders in women.


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

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

Sex differences in the lifetime incidence of psychiatric disorders vary from higher incidence in women, to no differences, to higher in men. Women/men lifetime incidence ratio was obtained directly from the publications referenced within the table or were calculated from the percentages of lifetime incidence published in the referenced studies. Superscripted letters next to each ratio reflects the citation from which we obtained such data: a, ref. 18; b, ref. 19; c, ref. 20; d, ref. 21; e, 22; f, ref. 23; g, ref. 24; h, ref. 25; i, ref. 26. *Of note, a sex bias for OCD is under debate and may depend on age; one study reports greater incidence among boys than girls. ADHD, attention deficit hyperactivity disorder; OCD, obsessive compulsive disorder; PTSD, posttraumatic stress disorder.27
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Sex differences in the lifetime incidence of psychiatric disorders vary from higher incidence in women, to no differences, to higher in men. Women/men lifetime incidence ratio was obtained directly from the publications referenced within the table or were calculated from the percentages of lifetime incidence published in the referenced studies. Superscripted letters next to each ratio reflects the citation from which we obtained such data: a, ref. 18; b, ref. 19; c, ref. 20; d, ref. 21; e, 22; f, ref. 23; g, ref. 24; h, ref. 25; i, ref. 26. *Of note, a sex bias for OCD is under debate and may depend on age; one study reports greater incidence among boys than girls. ADHD, attention deficit hyperactivity disorder; OCD, obsessive compulsive disorder; PTSD, posttraumatic stress disorder.27
Mentions: Epidemiological studies highlight significant differences between men and women in the incidence of psychiatric disorders (Figure 2). There is a higher incidence in men for autism, attention deficit hyperactivity disorder, schizophrenia and Parkinson's disease. Conversely, women are more susceptible to depression, anxiety and posttraumatic stress disorder (PTSD). In addition to differences in incidence, many psychiatric disorders are characterized by marked sex differences in progression and severity. Women are twice as likely to be diagnosed with PTSD;3, 4, 5, 6 have longer symptom duration,7 higher symptom severity and functional impairment,8 and have worse quality of life.9 Women with obsessive compulsive disorder are more likely to have more contamination/cleaning obsessions10 and their symptoms begin or worsen at menarche and postpartum.11 Women comprise 60% of individuals with generalized anxiety disorder and are more likely to develop comorbid psychiatric disorders and have worse prognosis and impairment.12,13 In addition to increased incidence of panic disorder in women, studies also suggest that panic attacks occur more frequently in women relative to men.14,15 Data indicate that women are at higher risk of developing anxiety disorders during reproductive life events such as menarche, menstruation, pregnancy, parturition and menopause.16,17 All together, these epidemiological data suggest that gonadal hormones may have a role in the onset of psychiatric disorders in women.

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