A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.

https://www.pnas.org/content/pnas/110/24/9950.full.pdf

Circadian patterns of gene expression in the human brain and disruption in major depressive disorder

The olfactory system in the brain plays key roles in the daily lives of humans and animals. This chapter briefly sketches the recent rapid progress in understanding the structure and function of the olfactory system and some unsolved important questions regarding this system. Olfactory perception occurs in discrete respirations (sniffs), and this chapter underscores the intimate relationship between the function of the olfactory system and the sniff rhythm. In addition, this chapter provides basic knowledge about the unique characteristics of the olfactory neural circuits, starting from olfactory sensory neurons in the nose through the olfactory bulb and olfactory cortex up to the orbitofrontal cortex and olfactory tubercle.

The Olfactory System

Forensic quest for age determination of bloodstains.

A thorough understanding of the physical and chemical changes that occur in the body after death is critical for accurate interpretation of gross and microscopic pathology at autopsy. Furthermore, knowledge of the postmortem processes and the factors that affect them will aid in the estimation of the postmortem interval (PMI). The estimation of the PMI is important in many human and animal death investigations. Despite many decades of research, accuracy in estimation of the time of death has not significantly improved, and no single method can be reliably used to accurately estimate the time of death. Great care should be taken when formulating such an estimate, for it is dependent on multiple circumstantial and environmental factors, and the accuracy and precision of the estimate decrease as the PMI increases. The majority of the research in the field has been conducted on human bodies, but many relevant conclusions may be drawn regarding the expected postmortem changes in animals and the estimation of the PMI. The veterinary pathologist must use great caution when attempting to extrapolate data and apply formulas designed for use in humans. Methods reviewed include gross changes, microscopic changes, temperature-based methods, postmortem chemistry, molecular methods, microbial assay, ocular changes, radiography, entomology, and others. Although only several of these methods are currently practical for use in the workup of cases, it is expected that future research will result in improved techniques with enhanced accuracy in the estimation of the PMI, which will benefit both human and veterinary forensic investigations.

https://journals.sagepub.com/doi/pdf/10.1177/0300985816629720

Postmortem Changes in Animal Carcasses and Estimation of the Postmortem Interval.

Forensic biochemistry for functional investigation of death: Concept and practical application

Estimation of the time of death based on the assessment of post mortem processes with emphasis on body cooling

This is a case report of a 30-year-old man found dead in his flat lying on the floor with multiple stab wounds over the body, surrounded by an extensive volume of blood. Examination of the scene of death showed a secure flat, locked from inside. A blood-stained knife was present close to the body and two unstained notes left on the sofa at the locus. A small plastic bag containing white powder (which following toxicological examinations appeared to be cocaine) and an almost full bottle of beer were present on a table. Autopsy revealed more than 40 stab wounds to neck, chest, and abdomen arranged in isolated groups within which the wounds showed similar directions and had a transverse orientation. Together with hesitation marks located on the neck and wrists these characteristics allowed to interpret this case as a suicide.

Multiple Self-Inflicted Stab Wounds to Neck, Chest and Abdomen as a Unique Manner of Suicide

In stressful situations, many animals release alarm pheromones to warn conspecifics of impending danger. The authors sought to establish experimental conditions for a larger study aimed at identifying alarm pheromones emitted by the rat. They placed rats in a specially designed chamber and exposed them to aversive tactile, visual and acoustic stimuli over the course of a few days. The researchers observed rats' behavior and analyzed air samples taken from their immediate environment under the following conditions: (i) when rats were unstressed; (ii) immediately after rats were exposed to aversive stimuli; and (iii) when rats were left alone in the chamber after being conditioned to fear imminent aversive stimuli. Stressed rats emitted several substances that are known to function as alarm pheromones in insects. When previously unstressed control rats were exposed to these same substances, they had a distinct behavioral fear response.

A preliminary study for identifying olfactory markers of fear in the rat.

Diagnostic problems with functional causes of death: analytical approaches and procedures.

The experiment was performed in pigs during which the postmortem body temperature was continuously measured. The study was focused on a period of time starting 0.5 hours after the animals' termination and consisted in computer recording of the cooling process of the eyeball (vitreous humor), orbit soft tissues, muscles, and the rectum. The experiment revealed the absence of a plateau phase of temperature decrease in eyeball and orbit soft tissues contrary to muscles and rectum, what demonstrates that temperature measurements in the eye could become an alternative method of determining the time of death during the initial phase of postmortem cooling. During this early postmortem period determination of the time of death based on measurements of the rectum or muscles temperatures due to existing plateau is not possible.

Gerhard Kernbach-Wighton

Papers

Estimation of the time of death based on the assessment of post mortem processes with emphasis on body cooling

Multiple Self-Inflicted Stab Wounds to Neck, Chest and Abdomen as a Unique Manner of Suicide

A preliminary study for identifying olfactory markers of fear in the rat.

Diagnostic problems with functional causes of death: analytical approaches and procedures.

The potential use of the eye temperature decrease in determining the time of death in the early postmortem period: studies in pigs.