Patients with mental disorders are at an elevated risk for developing aggressive behavior. In the last 19 years, the psychopharmacological treatment of aggression has changed dramatically because of the introduction of atypical antipsychotics into the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.Using a translational medicine approach, this review (part 1 of 2) examines the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis, namely, serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid, and also their respective receptors. The preclinical and clinical pharmacological studies concerning the role of these neurotransmitters have been reviewed, as well as research using transgenic animal models. The complex interaction among these neurotransmitters occurs at the level of brain areas and neural circuits such as the orbitoprefrontal cortex, anterior cortex, amygdala, hippocampus, periaqueductal gray, and septal nuclei, where the receptors of these neurotransmitters are expressed. The neurobiological mechanism of aggression is important to understand the rationale for using atypical antipsychotics, anticonvulsants, and lithium in treating aggressive behavior. Further research is necessary to establish how these neurotransmitter systems interact with brain circuits to control aggressive behavior at the intracellular level.

Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

Medial temporal lobe epilepsy (TLE), a condition known to affect the integrity and function of medial temporal lobe structures such as the hippocampus, has been shown to disrupt memory for real-life episodes. Here, patients with unilateral TLE, patients who received a unilateral temporal lobe resection to cure TLE, and healthy controls produced free narratives of autobiographical memories (AMs). To assess temporal resolution, narratives were segmented into bits of information, or details, which were classified according to how precisely they could be located within the time course of the AM. Categories included details corresponding to the entire AM, to parts or subevents within the AM, and to actions taking place within seconds to minutes. The number of details per category was tallied and compared between patients and controls. Temporal order was assessed by determining the correct (internally consistent) chronological order of the sequence of events within the narrative. Results indicate that while patients' memory for the parts or subevents of personal episodes was intact, as was their temporal order, their memory for the minute-by-minute unraveling of the episode was impaired. We believe this loss of temporally specific details may contribute to the reduced vividness of AM recollection in TLE patients. Our findings provide further evidence that patients with hippocampal damage retrieve skeletal AMs for which the gist of the memory is maintained, but the specific details are lost.

The normal range for the BUN:creatinine ratio (BCR) has not been determined for infants and children. The objectives of this study were to: (1) test the hypothesis that the BCR is higher in young children; and (2) establish normal BCR ranges for children of various ages. In this retrospective single-center review, 482 patients evaluated in an ambulatory setting were studied. The mean BCR declined significantly with age (P<0.0001). There was an inverse relationship between BCR and age, BMI, and serum creatinine and a direct relationship with BUN and GFRe. Based on our findings, we conclude that BCR values in adult patients are inapplicable to children below 10 years of age. We suggest that BCR greater than 60 in children ≤10 years and greater than 30 in children >10 years be considered abnormal. Application of age-specific pediatric criteria will ensure the proper application of the BCR in evaluating acutely ill children (word count: 150)