Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

While suicidal behaviour has been implicated in a plethora of psychiatric disorders including depression, psychoses and substance abuse, its association with adult ADHD is largely under-researched. Given that emotional instability and the high prevalence of comorbid conditions such as mood disorders and alcohol/drug dependence are typical for ADHD, the question of suicide risk must not be neglected in this patient group. A review of the current literature focusing on this issue provides strong evidence that ADHD patients are at a significant risk for experiencing suicidal ideations and committing suicide. For daily clinical practice, it is therefore essential to incorporate this aspect into the diagnostic and therapeutic process and to take preventive measures.

Agomelatine is an antidepressant with a unique mechanism of action. Since its marketing in 2009, concerns have been raised regarding its potential to induce liver injury. The authors therefore address the need to comprehensively evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case report. Recommendations for clinicians are also provided.In this review, agomelatine was found to be associated with higher rates of liver injury than both placebo and the four active comparator antidepressants used in the clinical trials for agomelatine, with rates as high as 4.6% for agomelatine compared to 2.1% for placebo, 1.4% for escitalopram, 0.6% for paroxetine, 0.4% for fluoxetine, and 0% for sertraline. The review also provides evidence for the existence of a positive relationship between agomelatine dose and liver injury. Furthermore, rates of liver injury were found to be lower in non-interventional studies. Findings from pharmacovigilance database reviews and one case report also highlight the risk of agomelatine-induced liver injury.As agomelatine does pose a risk of liver injury, clinicians must carefully monitor liver function throughout treatment. However, agomelatine’s unique mechanism of action and favourable safety profile render it a valuable treatment option.A quantitative analysis of agomelatine-induced liver injury is lacking in the literature and would be welcomed.

The neurobiology of suicidal behaviour, which constitutes one of the most serious problems both in psychiatry and general medical practice, still remains to a large degree unclear. As a result, scientists constantly look for new opportunities of explaining the causes underlying suicidality. In order to elucidate the biological changes occurring in the brains of the suicide victims, studies based on post-mortem brain tissue samples are increasingly being used. These studies employ different research methods to provide an insight into abnormalities in brain functioning on various levels, including gene and protein expression, neuroplasticity and neurotransmission, as well as many other areas. The aim of this paper to summarize the available data on the post-mortem studies, to provide an overview of main research directions and the most up-to-date findings, and to indicate the possibilities of further research in this field.

BackgroundThe neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3) could play a role in addictive behavior. Interactions between BDNF and dopamine transmission influence the alcohol intake. It has been hypothesized that extensive alcohol consumption leads to diminished circulating BDNF levels and impaired BDNF-mediated protective mechanisms. What is more, alcohol dependency causes changes in lipid metabolism which in turn may influence the neurotrophin system.MethodsIn this study, we tested the hypothesis that alcohol withdrawal increases the serum levels of BDNF in alcoholic patients and investigated correlations between serum BDNF and NT3 and alcohol in breath as well as with the body-mass-index (BMI), lipoprotein profiles and lifestyle factors in 110 male in-patients diagnosed with alcohol addiction on the first day after admission and at discharge.ResultsThe intoxication level (alcohol in breath at admission) was significantly correlated with liver enzymes and BDNF concentrations (R = .28; p = .004). Patients with positive breath-alcohol test at admission had about 9 times higher NT3 levels and higher liver enzyme concentration levels than nonintoxicated subjects. Alcohol intoxicated patients with pathological aspartate aminase (ASAT) levels had even higher NT3 level (F = 5.41; p = .022). The concentration of NT3 was positively associated with the (BMI) (admission R = .36; p = .004; discharge R = .33; p = .001), and the obese patients had 3 to 5 times higher NT3 concentration than the others. Low-density lipoprotein (LDL) concentration levels were found to positively correlate with NT3 concentration levels (admission R = .025; p = .015 discharge R = .24; p = .23).ConclusionOther than expected, the levels of NT3 and to a lesser extent BDNF levels, were found to be significantly increased in acute alcohol abuse. Alcohol deprivation did not significantly change the serum neurotrophin levels at admission. NT3 levels were positively correlated with the BMI and LDL levels. Because of expected difference between genders, we recommend investigating these correlations further in patients of both genders.