Sex differences in psychopathology: Of gonads, adrenals and mental illness

Solomon, M.B.; Herman, James P.

doi:10.1016/j.physbeh.2009.02.033

Cited by 227 publications

(188 citation statements)

References 151 publications

(175 reference statements)

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“…Dozens of reports indicate that females are vulnerable to affective disorders when dramatic estrogen fluctuation occurs (18,(23)(24)(25). Consistent with our current observation that immobility in the TST and FST in female mice changed as estrogen fluctuated (SI Appendix, Fig.…”

Section: Discussionsupporting

confidence: 91%

“…S10), a large body of evidence (18) demonstrates that depression-like behavior in the TST and FST varies as a function of the estrous cycle. Furthermore, there are several studies that report that estrogen replacement therapy is beneficial to women who suffered postpartum and perimenopausal affective disorders (18,26,27). We show here that E2 reverses CMS-induced behavioral modifications in female mice.…”

Section: Discussionsupporting

confidence: 57%

“…ERα is critical for reproductive function. In contrast, ERβ is important for modulating affective behaviors (18). The effects of E2 on hippocampal NO production, as we have shown, is mediated by ERβ.…”

Section: Discussionmentioning

confidence: 46%

“…The actions of estrogen are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ (17). Beneficial effects of estrogens on mood are mainly due to ERβ signaling (18). By incubating the cultured hippocampal neurons with ICI182,780 (a nonselective ER antagonist), 4,4′,4′′-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) (an ERα-selective agonist), or diarylpropionitrile (DPN) (an ERβ-selective agonist), we demonstrated that E2 promoted nNOS expression via activating ERβ (SI Appendix, Fig.…”

Section: Hippocampal No Is Essential For the Sex Difference Of Affectivementioning

confidence: 99%

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Hippocampal nitric oxide contributes to sex difference in affective behaviors

Luo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Mechanisms underlying the female preponderance in affective disorders are poorly understood. Here we show that hippocampal nitric oxide (NO) plays a role in the sex difference of depressionlike behaviors in rodents. Female mice had substantially lower NO production in the hippocampus and were significantly more likely to display negative affective behaviors than their male littermates. Eliminating the difference in the basal hippocampal NO level between male and female mice mended the sex gap of affective behaviors. Estradiol exerted a positive control on hippocampal NO production via estrogen receptor-β-mediated neuronal NO synthase expression. Thus, low estrogen in the female hippocampus accounts for lower local NO than in the male hippocampus. Although estrogen has important significance in modulating affective behaviors, it is not estrogen but NO in the hippocampus that mediates the sex difference of affective behaviors directly, because hippocampal NO was necessary for the behavioral effects of estradiol, and NO was an independent factor in modulating behaviors. Stress promoted hippocampal NO production in males because of glucocorticoid release, thus leading to local NO excess. In contrast, stress suppressed NO production in females because of decreased estrogen, thereby resulting in hippocampal NO shortage. Whereas activating cAMP response element binding protein (CREB) rescued the depression-like effects of the intrahippocampal NO donor diethylenetriamine/nitric oxide adduct (DETA/NONOate), inactivating CREB abolished the antidepressant-like effects of the intrahippocampal NO donor DETA/NONOate. Our findings suggest a molecular mechanism underlying the sex difference of affective behaviors.A ffective disorders such as depression and anxiety, lifethreatening and highly prevalent stress-related disorders, rank among the top causes of worldwide disease burden and disability (1, 2). It is commonly suggested that a female preponderance in depression and anxiety is universal and substantial. The prevalence of depression and anxiety for women is approximately twice that for men (2-6). Although there are advocates for the implications of hypothalamic-pituitary-adrenal axis hyperactivity in the sex differentiation in some expressions of both depression and anxiety (7), it is not clear what underlies the sex gap in these affective disorders.Neuronal nitric oxide synthase (nNOS) has been implicated in the psychiatric disorders characterized by depression (8, 9), schizophrenia (10), and aggressiveness (11). We recently demonstrated that hippocampal nNOS mediates the stress-related depressive behaviors of glucocorticoids (9) and the role of 5-hydroxytryptamine receptor 1A (5-HT1A) receptor in modulating anxiety-related behaviors (12). Evidence from clinical and biological studies indicates that the hippocampus plays an important role in major depression disorder (13). We found that chronic mild stress (CMS) increased hippocampal NO production by nNOS in male mice (6-9). In contrast, CMS diminished hippocampal NO prod...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 46%

Section: Hippocampal No Is Essential For the Sex Difference Of Affectivementioning

confidence: 99%

See 2 more Smart Citations

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Luo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…differences are not uncommon in anxiety and mood disorders (Bouchoucha et al, 2013;Solomon and Herman, 2009;Viswanath et al, 2011), future studies with a prospective design and a more equal female/male distribution are necessary to elaborate on our preliminary findings.…”

Section: Tablementioning

confidence: 83%

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

Kok

Sep

Veldhuijzen

et al. 2016

Journal of Affective Disorders

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a b s t r a c tBackground: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. Methods: Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/ or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. Results: PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. Limitations: The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. Conclusions: In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery.

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Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse

Lan,

Li,

Chen

et al. 2024

Advanced Science

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Exercise is considered as playing a pivotal role in the modulation of emotional responses. However, a precise circuit that mediates the effects of exercise on depression have yet to be elucidated. Here, a molecularly defined tri‐synaptic pathway circuit is identified that correlates motor inputs with antidepressant effects. With this pathway, initial inputs from neurons within the dorsal root ganglia (DRG) project to excitatory neurons in the gracile nucleus (GR), which in turn connect with 5‐HTergic neurons in the dorsal raphe nucleus (DRN), eventually coursing to excitatory pyramidal neurons within the medial prefrontal cortex (mPFC). Exercise activates this pathway, with the result that depressive‐ and anxiety‐like behaviors in mice are significantly reduced. In addition, it is found that exercise may exert antidepressant effects through regulating synaptic plasticity within this tri‐synaptic pathway. These findings reveal a hindbrain‐to‐forebrain neuronal circuit that specifically modulates depression and provides a potential mechanism for the antidepressant effects of exercise.

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Sex differences in psychopathology: Of gonads, adrenals and mental illness

Cited by 227 publications

References 151 publications

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse

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