Mounting evidence suggests that immune-system dysfunction and inflammation play a role in the pathophysiology and treatment of mood-disorders in general and of bipolar disorder in particular. The current study examined the effects of chronic low-dose aspirin and low-dose lithium (Li) treatment on plasma and brain interleukin-6 and tumor necrosis factor-α production in lipopolysaccharide (LPS)-treated rats. Rats were fed regular or Li-containing food (0.1%) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. On days 21 and 42 rats were injected with 1 mg/kg LPS or saline. Two h later body temperature was measured and rats were sacrificed. Blood samples, the frontal-cortex, hippocampus, and the hypothalamus were extracted. To assess the therapeutic potential of the combined treatment, rats were administered the same Li + aspirin protocol without LPS. We found that the chronic combined treatment attenuated LPS-induced hypothermia and significantly reduced plasma and brain cytokine level elevation, implicating the potential neuroinflammatory diminution purportedly present among the mentally ill. The combined treatment also significantly decreased immobility time and increased struggling time in the forced swim test, suggestive of an antidepressant-like effect. This preclinical evidence provides a potential approach for treating inflammation-related mental illness.

Background: Over the past 20 years, Jewish and Bedouin civilians in southern Israel have faced the ongoing threat of missile attacks from Gaza, with possible mental health consequences. This study aimed to assess the prevalence of post-traumatic stress disorder (PTSD) among Jewish and Bedouin adult civilians in southern Israel in a period with few missile attacks from Gaza, and no military operations. Methods: The study population included 389 participants (246 Jews, 143 Bedouins) living within 40 km/25 mi from Gaza for at least 2 years and interviewed between January and March 2023 (before the ongoing war that started on October 7th, 2023). The PTSD Checklist (PCL-5) was used, with a score of 33 as a cutoff point for the presence of PTSD. Results: Compared to Jews, a significantly lower proportion of Bedouins reported accessibility to bomb shelters and siren warning systems. Overall, 20.3% of the respondents exhibited PTSD. Multivariate analysis revealed that after adjustment for demographic and household characteristics, Bedouins had a six-fold significantly higher probability of PTSD in comparison to Jews (OR 5.6, 95%CI 2.8–10.8). Compared to participants with high socioeconomic status (SES), participants with low SES had a six-fold significantly higher probability of PTSD (OR 6.0, 95%CI 2.2–16.5). Participants who did not have an alarm system had more than two-fold odds for PTSD (OR 2.3, 95%CI 1.1–5.5). Being single, living in urban areas, or having a disability significantly increased the probability of PTSD. Conclusions: The findings of this study demonstrate a significantly higher prevalence of PTSD among the Bedouin population of Southern Israel. Several sociodemographic characteristics were associated with the increased prevalence of PTSD, the most prominent of which was low SES. Healthcare professionals and authorities should be proactive in screening for PTSD, and provide tailored treatment and support, taking into account ethnical and cultural background. Authorities should address the disparity in bomb shelter access and siren warning coverage between Bedouin and Jewish communities.

Despite established efficacy in bipolar disorder patients, lithium (Li) therapy has serious side effects, particularly chronic kidney disease. We examined the safety and behavioral effects of combined chronic low-dose aspirin plus low-dose Li in rats to explore the toxicity and therapeutic potential of this treatment. Rats were fed regular or Li-containing food (0.1% [low-dose, LLD-Li] or 0.2% [standard-dose, STD-Li]) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. Renal function and gastric mucosal integrity were assessed. The effects of the combination treatment were evaluated in depression-like and anxiety-like behavioral models. Co-treatment with aspirin did not alter plasma Li levels. Chronic STD-Li treatment resulted in significant polyuria and polydipsia, elevated blood levels of creatinine and cystatin C, and increased levels of kidney nephrin and podocin—all suggestive of impaired renal function. Aspirin co-treatment significantly damped STD-Li-induced impairments in kidney parameters. There were no gastric ulcers or blood loss in any treatment group. Combined aspirin and LLD-Li resulted in a significant increase in sucrose consumption, and in the time spent in the open arms of an elevated plus-maze compared with the LLD-Li only group, suggestive of antidepressant-like and anxiolytic-like effects, respectively. Thus, we demonstrate that low-dose aspirin mitigated the typical renal side effects of STD-Li dose and enhanced the beneficial behavioral effects of LLD-Li therapy without aggravating its toxicity.

Antimanic treatment,bipolar disorder,mania,protein kinase C,tamoxifen