What do we know about sex differences in depression: A review of animal models and potential mechanisms

Ma, Lei; Xu, Yong; Wang, Gang; Li, Rena

doi:10.1016/j.pnpbp.2018.08.026

Cited by 55 publications

(25 citation statements)

References 104 publications

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“…In addition, preclinical and clinical evidence suggest that patients with depression tend to present lower levels of serum BDNF when compared to healthy individuals (Wilkinson et al, 2018; Ma et al, 2019), which may be reversed after antidepressant drug treatment (Brunoni et al, 2017; Molendijk et al, 2018). Baseline alterations in serum BDNF levels in depressive patients is not a consensus in the literature (Jevtović et al, 2011; Molendijk et al, 2011; Papakostas et al, 2011; Elfving et al, 2012) and changes in BDNF levels after treatment seem to depend on the antidepressant class (Kreinin et al, 2015; Sheldrick et al, 2017; Wilkinson et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

et al. 2019

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Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatmentresistant depression. Preclinical and clinical studies have suggested that serum brainderived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

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Section: Introductionmentioning

confidence: 99%

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

et al. 2019

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“…In general, mental disorders assessed in this study showed considerably higher prevalence in women, across the three study sites and different age brackets, corroborating other studies showing differences between males and females in the occurrence of these mental disorders (higher in women) 34,52 . Women's greater susceptibility to depression and anxiety is still poorly understood, although frequently related to cultural and social determinants, as well as to neuroendocrine factors, especially the influence of sex hormones and their fluctuations 53,54 . It is also possible that part of the excess in mental disorders among women in Brazil is explained by issues related to gender violence, whether or not perpetrated by the intimate partner.…”

Section: Discussionmentioning

confidence: 99%

Transtornos mentais em adolescentes, jovens e adultos do Consórcio de Coortes de Nascimento brasileiras RPS (Ribeirão Preto, Pelotas e São Luís)

et al. 2020

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Resumo: Embora se reconheça que depressão e ansiedade resultem em incapacidades, bem como em prejuízos laborais e para os sistemas de saúde, pesquisas de base populacional são escassas no Brasil. Este estudo avaliou a prevalência de transtornos mentais em adolescentes, jovens e adultos e sua relação com características sociodemográficas em cinco coortes de nascimento (RPS): Ribeirão Preto (São Paulo), Pelotas (Rio Grande do Sul) e São Luís (Maranhão), Brasil. Episódio depressivo, risco de suicídio, fobia social e transtorno de ansiedade generalizada foram avaliados usando-se o Mini International Neuropsychiatric Interview. Intervalos de confiança bootstrap foram estimados e prevalências estratificadas por sexo e nível socioeconômico no programa R. Foram incluídos 12.350 participantes das coortes. Episódio depressivo maior atual foi mais prevalente em adolescentes de São Luís (15,8%; IC95%: 14,8-16,8) e nos adultos de Ribeirão Preto (12,9%; IC95%: 12,0-13,9). As maiores prevalências para risco de suicídio ocorreram nos adultos de Ribeirão Preto (13,7%; IC95%:12,7-14,7), fobia social e ansiedade generalizada nos jovens de Pelotas com 7% (IC95%: 6,3-7,7) e 16,5% (IC95%: 15,4-17,5), respectivamente. As menores prevalências de risco de suicídio ocorreram nos jovens de Pelotas (8,8%; IC95%: 8,0-9,6), fobia social nos jovens de Ribeirão Preto (1,8%; IC95%: 1,5-2,2) e ansiedade generalizada nos adolescentes de São Luís (3,5%; IC95%: 3,0-4,0). Em geral, os transtornos mentais foram mais prevalentes nas mulheres e naqueles com menor nível socioeconômico, independentemente do centro e idade, reforçando a necessidade de maior investimento em saúde mental no Brasil, sem desconsiderar determinantes de gênero e socioeconômicos.

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“…Almost always, rat and mouse are used to model depression [39][40][41][42][43][44][45][46][47][48][49][50]. Forced swimming test, tail suspension test, open field test, and hot plate test are among the most known tests of evaluating depression in the previously mentioned models [50][51][52][53][54]. Although these are creative and decent models, however, how could someone compare a so-called depressed male rat behavior and attitude with the depression in Franz Kafka or Friedrich Nietzsche?…”

Section: Depression: It Is Neither All About Men Nor About Male Ratsmentioning

confidence: 99%

“…Furthermore, post-menopausal depression is catecholamine-dependent, while depression in women in the productive age is serotonin prominent. That is why venlafaxine is suitable for elderly depressed women, and fluoxetine and sertraline have nothing to do with them but are the drug of choice for depressed men [51][52][53]. All these happened since studies on depression were almost always conducted exclusively on men; unfortunately, scientists preferred to avoid menstrual cyclic depressions, and eliminated women, even when raised FDA approval.…”

Section: Depression: It Is Neither All About Men Nor About Male Ratsmentioning

confidence: 99%

Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

Seifirad

Haghpanah

2019

EPMA Journal

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Preclinical investigations such as animal modeling make the basis of clinical investigations and subsequently patient care. Predictive, preventive, and personalized medicine (PPPM) not only highlights a patient-tailored approach by choosing the right medication, the right dose at the right time point but it as well essentially requires early identification, by the means of complex and state-of-the-art technologies of unmanifested pathological processes in an individual, in order to deliver targeted prevention early enough to reverse manifestation of a pathology. Such an approach can be achieved by taking into account clinical, pathological, environmental, and psychosocial characteristics of the patients or an individual who has a suboptimal health condition. Inappropriate modeling of chronic and complex disorders, in this context, may diminish the predictive potential and slow down the development of PPPM and consequently modern healthcare. Therefore, it is the common goal of PPPM and translational medicine to find the solution for the problem we present in our review. Both, translational medicine and PPPM in parallel, essentially need accurate surrogates for misleading animal models. This study was therefore undertaken to provide shreds of evidence against the validity of animal models. Limitations of current animal models and drug development strategies based on animal modeling have been systematically discussed. Finally, a variety of potential surrogates have been suggested to change the unfavorable situation in medical research and consequently in healthcare.

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What do we know about sex differences in depression: A review of animal models and potential mechanisms

Cited by 55 publications

References 104 publications

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

Transtornos mentais em adolescentes, jovens e adultos do Consórcio de Coortes de Nascimento brasileiras RPS (Ribeirão Preto, Pelotas e São Luís)

Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

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