No abstract

Given the failure to develop disease-modifying therapies for Alzheimer’s disease (AD), strategies aiming at preventing or delaying the onset of the disease are being prioritized. While the debate regarding whether depression is an etiological risk factor or a prodrome of AD rages on, a key determining factor may be the timing of depression onset in older adults. There is increasing evidence that untreated early-onset depression is a risk factor and that late-onset depression may be a catalyst of cognitive decline. Data from animal studies have shown a beneficial impact of selective serotonin reuptake inhibitors on pathophysiological biomarkers of AD including amyloid burden, tau deposits and neurogenesis. In humans, studies focusing on subjects with a prior history of depression also showed a delay in the onset of AD in those treated with most selective serotonin reuptake inhibitors. Paroxetine, which has strong anticholinergic properties, was associated with increased mortality and mixed effects on amyloid and tau deposits in mice, as well as increased odds of developing AD in humans. Although most of the data regarding selective serotonin reuptake inhibitors is promising, findings should be interpreted cautiously because of notable methodological heterogeneity between studies. There is thus a need to conduct large scale randomized controlled trials with long follow up periods to clarify the dose-effect relationship of specific serotonergic antidepressants on AD prevention.

Our study's objective is to determine whether substance use disorders’ association with aggression differs according to the type of substance and/or the form of aggression, within the same population. We used data from the National Survey on Drug Use and Health across 2008–2014, with a pooled sample of 270,227 adult respondents. We used regression models to estimate the odds ratios for those having alcohol and/or drug use disorder(s) perpetrating (a) each form of aggression compared with no aggression and (b) other‐directed compared with self‐directed aggression. Alcohol use disorder alone and drug use disorder(s) alone were both associated with significantly increased odds of committing self‐directed, other‐directed, and combined aggression. Individuals with drug use disorder(s) alone were more likely to commit other‐directed than self‐directed aggression (adjusted odds ratio = 1.46, 95% CI = 1.04–2.05). Individuals with alcohol use disorder alone were not likely to commit one over the other (adjusted odds ratio = 1.20, 95% CI = 0.90–1.61). In conclusion, the integrated model of aggression based on the stress–diathesis model is a relevant framework to study risk factors for aggression. Further research is needed to identify longitudinal predictors of directionality of aggression.

Objectives Monoclonal antibodies such as antagonists of tumor necrosis factor-alpha have been shown to have beneficial effects on the well-being of patients with inflammatory illnesses. However, mood episodes triggered by such agents have been reported. We herein report the case of mania induced by adalimumab treatment in an adult with ankylosing spondylitis, which later resolved once adalimumab was discontinued and mood stabilizers were initiated. Methods A 25-year-old man, with prior history of dysthymia, was diagnosed with ankylosing spondylitis and started on adalimumab. He gradually developed manic symptoms over seven to eight months, while maintained on adalimumab. As his condition did not improve with outpatient management, the patient was admitted to the Psychiatry inpatient unit. Results Valproate and aripiprazole were initiated, and adalimumab was substituted with non-steroidal anti-inflammatory agents. Mood symptoms resolved within days, and the patient was discharged. Upon follow-up, the patient was euthymic and compliant to his psychotropic medications. He was started on certolizumab, a different immunomodulatory, for his ankylosing spondylitis. Conclusions Immunological modulation might be a key factor in triggering, maintaining, or treating mood symptoms. Further research in this field is warranted to better understand the pathophysiology of mania. To our knowledge, manic symptoms induced by adalimumab have not been previously reported in the literature, which is why our case report can have an impact in recognizing this important clinical adverse effect.