ABSTRACT
The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition.
Subject(s)
Alleles , Amidohydrolases/genetics , Combat Disorders/genetics , Genetic Predisposition to Disease/genetics , Head Injuries, Penetrating/genetics , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide/genetics , Stress Disorders, Post-Traumatic/genetics , Veterans/psychology , Vietnam Conflict , Adolescent , Adult , Aged , Child , Child Abuse/psychology , Combat Disorders/diagnosis , Combat Disorders/epidemiology , Combat Disorders/psychology , Cross-Sectional Studies , Defense Mechanisms , Genotype , Head Injuries, Penetrating/diagnosis , Head Injuries, Penetrating/epidemiology , Humans , Image Interpretation, Computer-Assisted , Life Change Events , Male , Mental Recall/physiology , Middle Aged , Prefrontal Cortex/injuries , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Tomography, X-Ray ComputedABSTRACT
In recent years, an increasing number of neuroimaging studies have sought to identify the brain anomalies associated with mood and anxiety disorders. The results of such studies could have significant implications for the development of novel treatments for these disorders. A challenge currently facing the field is to assimilate the large and growing corpus of imaging data to inform a systems-level model of the neural circuitry underlying the disorders. One prominent theoretical perspective highlights the top-down inhibition of amygdala by ventromedial prefrontal cortex (vmPFC) as a crucial neural mechanism that may be defective in certain mood and anxiety disorders, such as major depression and post-traumatic stress disorder. In this article, we provide a critical review of animal and human data related to this model. In particular, we emphasize the considerable body of research that challenges the veracity (or at least completeness) of the predominant model. We propose a framework for constructing a more comprehensive model of vmPFC function, with the goal of fostering further progress in understanding the neuropathophysiological basis of mood and anxiety disorders.
Subject(s)
Anxiety Disorders/pathology , Mood Disorders/pathology , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Animals , Disease Models, Animal , Humans , Models, Biological , Neural Pathways/physiology , NeuroimagingABSTRACT
In recent years, an increasing number of neuroimaging studies have sought to identify the brain anomalies associated with psychopathy. The results of such studies could have significant implications for the clinical and legal management of psychopaths, as well as for neurobiological models of human social behavior. In this article, we provide a critical review of structural and functional neuroimaging studies of psychopathy. In particular, we emphasize the considerable variability in results across studies, and focus our discussion on three methodological issues that could contribute to the observed heterogeneity in study data: (1) the use of between-group analyses (psychopaths vs non-psychopaths) as well as correlational analyses (normal variation in 'psychopathic' traits), (2) discrepancies in the criteria used to classify subjects as psychopaths and (3) consideration of psychopathic subtypes. The available evidence suggests that each of these issues could have a substantial effect on the reliability of imaging data. We propose several strategies for resolving these methodological issues in future studies, with the goal of fostering further progress in the identification of the neural correlates of psychopathy.
Subject(s)
Antisocial Personality Disorder/pathology , Antisocial Personality Disorder/physiopathology , Brain/pathology , Brain/physiopathology , Antisocial Personality Disorder/diagnosis , Brain Mapping/methods , Humans , Magnetic Resonance Imaging/methods , Reproducibility of ResultsABSTRACT
Ascending and descending procedures were used to obtain speech reception thresholds from 32 normal-hearing subjects whereas digits and spondee words were used as test materials. Comparisons of thresholds were made for the two procedures and materials. Results indicated that slightly lower (less SPL) speech thresholds resulted from the use of a descending procedure with both types of material. In addition, digit material was found to yield generally lower threshold values than spondees. Advantages to the use of the two procedures and materials are discussed.
