Sex differences in the incidence of antidepressant-induced mania (AIM) in bipolar disorders

Williams, Ann E.; McInnis, Melvin G.

doi:10.1038/s41386-018-0216-4

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…Sex-specific neuronal circuitry, genetic risk, and endocrine abnormalities might contribute to the biological vulnerability for antidepressant-induced activation in female patients. 16,19 A recent study by Scott and colleagues (2017) concluded that the differential risk factor should be taken into account for antidepressant-associated mania between men and women. 25 They demonstrated while the striking risk factor for male patients is comorbid alcohol use disorder, thyroid disorder is one of the strongest risk factors for female patients.…”

Section: Discussionmentioning

confidence: 99%

“…13 Some authors have also suggested that women with BD were more likely to receive antidepressants and female sex is a significant risk factor for manic switch. [16][17][18][19] Besides, in the extant literature of PBD, a population-based study by Martin et al (2004) proposed peripubertal children were more susceptible to antidepressantinduced manic conversion, compared to the older age groups. 20 Strawn et al (2014) also investigated adverse reactions causing antidepressant discontinuation (eg, irritability, hyperactivity, aggression, and impulsivity) among younger BD offspring.…”

Section: Introductionmentioning

confidence: 99%

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Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder

İnal

Ermiş

Koç

et al. 2021

Acta Psychiatr Scand

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Objective: Pediatric bipolar disorder (PBD) is a serious, recurrent disorder leading to severe functional impairment. As a first mood episode, index episode could affect the long-term course of the illness. This study aimed to investigate the clinical characteristics of youth with PBD from our multicenter, nationwide, naturalistic followup samples and to identify (i) the effects of index mood episode and (ii) the effect of previous antidepressant treatments on the age at mania onset of PBD. Method:The study sample consisted of 271 youth with BD-I followed by the child and adolescent psychiatry clinics of seven different university hospitals and three research state hospitals, representing six geographic regions across Turkey. All diagnoses were made according to structured interviews, and all data were retrospectively obtained from clinical records by the clinicians.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder

İnal

Ermiş

Koç

et al. 2021

Acta Psychiatr Scand

View full text Add to dashboard Cite

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“…Another possible rationalization is sex-related differences in medication response, possibly relating to the impact of androgen levels on LTMA mediation ( 56 ), as well as the female sex hormones relating to allergic manifestations ( 57 ). In this context, a major limitation of many preclinical pharmacological studies is the exclusive inclusion of only male animals, neglecting half of the possible consumers of pharmacological treatments ( 51 – 54 , 58 – 63 ). This underscores the necessity to evaluate effects of LTMAs (such as MTK) in both male and female subjects.…”

Section: Introductionmentioning

confidence: 99%

“…Reports show LT inhibitors ascertaining only modest therapeutic efficacy (49,50). Suggested explanations for this include: individual differences in LT levels, heterogeneity of disease phenotypes, and, differences in drug pharmacokinetics, pharmacodynamics and pharmacogenomics (51)(52)(53)(54)(55). Another possible rationalization is sex-related differences in medication response, possibly relating to the impact of androgen levels on LTMA mediation (56), as well as the female sex hormones relating to allergic manifestations (57).…”

Section: Introductionmentioning

confidence: 99%

Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats

et al. 2022

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BackgroundAccumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes’ (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.ObjectiveThis study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats.MethodsDepression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2.ResultsOverall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent.ConclusionContrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment.

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“…Studies investigating sex differences in patients with BD have also provided interesting findings. While prevalence rates of BDs have generally been reported to be similar between males and females, 9 symptomatic differences have been commonly reported. Azorin et al 10 reported a number of sex‐based symptomatic differences in patients with BD including females being more likely to initially present with depressive symptoms and their depressive symptoms continuing to be a dominant feature, while conversely for males, mania was a dominant feature.…”

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confidence: 98%

Sex differences in fronto‐limbic white matter tracts in youth with mood disorders

Hermens

Jamieson

Fitzpatrick

et al. 2022

Psychiatry Clin Neurosci

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Aims Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders. Methods Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self‐report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto‐limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors. Results Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed. Conclusions Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.

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Sex differences in the incidence of antidepressant-induced mania (AIM) in bipolar disorders

Cited by 5 publications

References 6 publications

Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder

Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder

Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats

Sex differences in fronto‐limbic white matter tracts in youth with mood disorders

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