Sex differences in stress regulation of arousal and cognition

doi:10.1016/j.physbeh.2017.09.025

Physiology & Behavior

Volume 187, 1 April 2018, Pages 42-50

https://doi.org/10.1016/j.physbeh.2017.09.025 Get rights and content

Highlights

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We propose that stress biases males and females towards different disorders.
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Psychiatric disorders with hyperarousal symptoms are common in women.
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Increased stress sensitivity of an arousal center in females helps explain this bias.
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Psychiatric disorders with cognitive deficits are common in men.
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Male vulnerability to stress regulation of cognition likely contributes to this bias.

Abstract

There are sex differences in the prevalence and presentation of many psychiatric disorders. For example, posttraumatic stress disorder (PTSD) and major depression are more common in women than men, and women with these disorders present with more hyperarousal symptoms than men. In contrast, attention deficit hyperactivity disorder (ADHD) and schizophrenia are more common in men than women, and men with these disorders have increased cognitive deficits compared to women. A shared feature of the aforementioned psychiatric disorders is the contribution of stressful events to their onset and/or severity. Here we propose that sex differences in stress responses bias females towards hyperarousal and males towards cognitive deficits. Evidence from clinical and preclinical studies is detailed. We also describe underlying neurobiological mechanisms. For example, sex differences in stress receptor signaling and trafficking in the locus coeruleus-arousal center are detailed. In learning circuits, evidence for sex differences in dendritic morphology is provided. Finally, we describe how evaluating sex-specific mechanisms for responding to stress in female and male rodents can lead to better treatments for stress-related psychiatric disorders.

Section snippets

Sex differences in psychiatric disorders

Many neuropsychiatric disorders affect women and men differently. There are differences in the rates at which some of these disorders occur. For example, women are more likely than men to be diagnosed with posttraumatic stress disorder (PTSD) and major depression [1], [2], [3], while men are more likely than women to be diagnosed with attention deficit hyperactivity disorder (ADHD) and schizophrenia [4], [5], [6]. There are also sex differences in the presentation of these disorders, such that

Female vulnerability to stress-induced hyperarousal: Evidence from human studies

Hyperarousal is a dysregulated state of persistently being “on-edge” that contributes to increased agitation, restlessness, a lack of concentration, and sleep disruption. As noted, hyperarousal distinguishes a symptom cluster of PTSD and contributes to symptoms of depression [12]. Not only is there a female bias in these disorders [1], [2], [3], but, compared to men with PTSD and depression, women with the same disorders have greater hyperarousal symptoms, including disrupted sleep [7], [39],

Female vulnerability to stress-induced hyperarousal: Evidence from animal studies

Animal studies have revealed further sex differences in the LC and its regulation by stress (for review see [60]). In addition to its larger size in females than males of certain rat strains [55], [56], we found that dendrites of LC neurons are longer and more complex in female compared to male rats [61] (Fig. 1a,b). LC dendrites are present within the nuclear core of the LC, but they also extend into the ventromedial and dorsolateral pericoerulear (peri-LC) regions [62], [63]. Inputs into the

Male vulnerability to stress-induced cognitive deficits: Evidence from human studies

Schizophrenia and ADHD are chiefly characterized by disruptions in cognition. These disorders affect men more frequently than women, and there are also sex differences in symptomatology [6], [92], [93]. In patients with schizophrenia, most studies indicate that men have greater cognitive deficits than women [6], [94], [95], [96]. Sex differences in verbal memory deficits in schizophrenia patients are linked to distinct structural changes in the brains of men versus women [97]. Unlike female

Male vulnerability to stress-induced mnemonic deficits: Evidence from animal studies

Many studies have investigated how stress affects learning and memory in animal models, and some have considered sex differences. A portion of this literature focuses on prenatal or perinatal stress, and, generally, exposure to chronic stress early in development alters cognitive processes more in male than female rodents [34], [120], [121], [122]. In addition to early life stress, other studies have focused on how exposure to an acute stressor alters learning and memory in both sexes. For

Gonadal hormone regulation of stress effects on attention: Evidence from animal studies

Many studies investigating sex differences in the effects of stress on cognition have focused on mnemonic processes. Recently, our laboratory has been interested in whether stress alters attention in female and male rats. Specifically we wanted to determine whether CRF altered attention. A previous study found that central administration of CRF altered selective and divided attention in male rats [155], but we wanted to determine the effect of CRF on sustained attention, the ability to monitor

Implications and conclusions

The processes that underlie psychiatric disorders and cause sex differences therein are complex. The data presented here highlight that one contributing factor is sex differences in responses to stress. This emerging research suggests that stress biases females towards hyperarousal and males towards altered cognition. These data suggest that interventions designed to mitigate the effects of stress would be helpful in treating certain psychiatric disorders. Although such interventions have been

Funding Sources

This work was supported by the National Science Foundation [grant number IOS-1552416] and Pennsylvania's Commonwealth Universal Research Enhancement Program [grant number 420792].

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Sex differences in stress regulation of arousal and cognition

Highlights

Abstract

Section snippets

Sex differences in psychiatric disorders

Female vulnerability to stress-induced hyperarousal: Evidence from human studies

Female vulnerability to stress-induced hyperarousal: Evidence from animal studies

Male vulnerability to stress-induced cognitive deficits: Evidence from human studies

Male vulnerability to stress-induced mnemonic deficits: Evidence from animal studies

Gonadal hormone regulation of stress effects on attention: Evidence from animal studies

Implications and conclusions

Funding Sources

Neurosci. Biobehav. Rev.

Schizophr. Res.

Schizophr. Res.

Front. Neuroendocrinol.

Trends Neurosci.

Neuropharmacology

Neurobiol. Learn. Mem.

Horm. Behav.

Compr. Psychiatry

Neuroscience

J. Affect. Disord.

Schizophr. Res.

J. Psychiatr. Res.

Eur. J. Pharmacol.

Neurosci. Biobehav. Rev.

Neurobiol. Stress

Pharmacol. Biochem. Behav.

J. Affect. Disord.

J. Affect. Disord.

Personal. Individ. Differ.

NeuroImage

NeuroImage

Gastroenterology

NeuroImage

Neurobiol. Aging

Neurobiol. Aging

Brain Res.

Brain Res.

Brain Res.

Brain Res. Dev. Brain Res.

Brain Res. Bull.

Physiol. Behav.

Neuroscience

Eur. J. Pharmacol.

Physiol. Behav.

Brain Res.

Biol. Psychiatry

Neurosci. Lett.

Brain Res. Bull.

Trends Pharmacol. Sci.

Biochem. Biophys. Res. Commun.

Biol. Psychiatry

NeuroImage

Psychiatry Res.

J. Am. Acad. Child Adolesc. Psychiatry

Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States

Int. J. Methods Psychiatr. Res.

The epidemiology of trauma, PTSD, and other posttrauma disorders

Trauma Violence Abuse

Sex differences in trauma and posttraumatic stress disorder: a quantitative review of 25 years of research

Psychol. Bull.

Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11

J. Am. Acad. Child Adolesc. Psychiatry

Systematic review and collaborative recalculation of 133 693 incident cases of schizophrenia

Psychol. Med.