Classifying the manner of death in drug/ethanol overdose in equivocal cases: a suggested future tool for medical examiners using neuroanatomical markers

The purpose of the present thesis was to propose a guideline to differentiate between an accidental or suicide manner of death when dealing with a drug/ethanol overdose in which all available medical and investigational evidence, including a psychological autopsy, is inconclusive, thereby resulting in an undetermined manner of death. An in-depth literature review was conducted in the field of neuroscience, psychiatry, and pharmacology to discover neuroanatomical markers indicative of suicidal behavior in the context of two major risk factors of suicide, stress and depression, and two hypotheses behind the cause of suicidal behavior, impulsive aggression and neuronal plasticity. The neuroanatomical markers of suicidal behavior, as indicated by the experimental evidence of various studies in suicide subjects, included serotonergic dysfunction, hypothalamic-pituitary-adrenal axis hyperactivity, brain-derived neurotrophic factor deficiency, and the associated anatomical changes in the v brain. Upon consideration of the forensic applicability of analyzing these neuroanatomical markers indicative of suicidal behavior, a guideline was generated to differentiate between an accidental and suicide manner of death by showing suicide subjects had significantly decreased messenger ribonucleic acid and protein levels of presynaptic serotonin receptors along with significantly increased messenger ribonucleic acid and protein levels of postsynaptic serotonin receptors in the prefrontal cortex, significantly decreased serum brainderived neurotrophic factor levels, and significantly decreased messenger ribonucleic acid and protein levels of brain-derived neurotrophic factor and tyrosine kinase B receptors in the prefrontal cortex and hippocampus when compared to the levels of both depressed non-suicidal individuals and healthy controls. Given the significant difference observed between suicide subjects and controls, these differences in neuroanatomical markers may play an important role in the pathophysiology of suicidal behavior and have the potential to be used in establishing the intention of an individual in an overdose death to distinguish between an accidental or suicidal manner of death.