Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing and Analysis Consortium published in late 2005. Neuroevolutionary insights relevant to fear circuitry symptoms that primarily emerge overconsolidationally (especially Combat related Posttraumatic Stress Disorder) are presented. Also introduced is a human-evolution-based principle for clustering innate fear traits. The "Neuroevolutionary Time-depth Principle" of innate fears proposed in this article may be useful in the development of a neuroevolution-based taxonomic re-clustering of stress-triggered and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear circuits are proposed based on their time-depths: 1) Mesozoic (mammalian-wide) circuits hardwired by wild-type alleles driven to fixation by Mesozoic selective sweeps; 2) Cenozoic (simian-wide) circuits relevant to many specific phobias; 3) mid Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic circuits (arguably mostly related to stabilizing selection driven by gene-culture co-evolution). More importantly, the author presents evolutionary perspectives on warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational-Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time-depth Principle presented in this article may help explain the dissimilar stress-resilience levels following different types of acute threat to survival of oneself or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD rates following exposure to lethal inter-group violence (combat, warzone exposure or intentionally caused disasters such as terrorism) are usually 5-10 times higher than rates following large-scale natural disasters such as forest fires, floods, hurricanes, volcanic eruptions, and earthquakes. The author predicts that both intentionally-caused large-scale bioevent-disasters, as well as natural bioevents such as SARS and avian flu pandemics will be an exception and are likely to be followed by PTSD rates approaching those that follow warzone exposure. During bioevents, Amygdala-driven and locus-coeruleus-driven epidemic pseudosomatic symptoms may be an order of magnitude more common than infection-caused cytokine-driven symptoms. Implications for the red cross and FEMA are discussed. It is also argued that hospital phobia as well as dog phobia, bird phobia and bat phobia require re-taxonomization in DSM-V in a new "overconsolidational disorders" category anchored around PTSD. The overconsolidational spectrum category may be conceptualized as straddling the fear circuitry spectrum disorders and the affective spectrum disorders categories, and may be a category for which Pitman's secondary prevention propranolol regimen may be specifically indicated as a "morning after pill" intervention. Predictions are presented regarding obsessive-compulsive disorder (OCD) (e.g., female-pattern hoarding vs. male-pattern hoarding) and "culture-bound" acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook yong, suo yang, rok-joo, jinjinia-bemar, karoshi, gwarosa, Voodoo death). Also discussed are insights relevant to pseudoneurological symptoms and to the forthcoming Dissociative-Conversive disorders category in DSM-V, including what the author terms fright-triggered acute pseudo-localized symptoms (i.e., pseudoparalysis, pseudocerebellar imbalance, psychogenic blindness, pseudoseizures, and epidemic sociogenic illness). Speculations based on studies of the human abnormal-spindle-like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection-Injury Phobia." Finally, the author argues for a non-reductionistic fusion of "distal (evolutionary) neurobiology" with clinical "proximal neurobiology," utilizing neurological heuristics. It is noted that the value of re-clustering fear traits based on behavioral ethology, human-phylogenomics-derived endophenotypes and on ontogenomics (gene-environment interactions) can be confirmed or disconfirmed using epidemiological or twin studies and psychiatric genomics

Evolution of the human fear-circuitry and acute sociogenic pseudoneurological symptoms: The Neolithic balanced-polymorphism hypothesis

In light of the increasing threat of large-scale massacres such as terrorism against non-combatants (civilians), more attention is warranted not only to posttraumatic stress disorder (PTSD) but also to acute sociogenic pseudoneurological ("conversion") symptoms, especially epidemic sociogenic symptoms. We posit that conversion disorders are etiologically related to specific evolutionary pressures (inescapable threats to life) in the late stage of the human environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued that from the neuroevolutionary perspective, medically unexplained efferent vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in young otherwise healthy individuals, may be taxonomized as stress and fear-circuitry disorders. In the present article, we extend neuroevolutionary perspectives to acute pseudoneurological sociogenic ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these perplexing pseudoneurological stress-triggered symptoms, which constitute psychopathology in extant humans, are traceable to allele-variant polymorphisms which spread during the Neolithic EEA. During Neolithic warfare, conversive symptoms may have increased the survival odds for some non-combatants by visually (i.e., "non-verbally") signaling to predatory conspecifics that one does not present a danger. This is consistent with the age and sex pattern of conversive disorders. Testable and falsifiable predictions are presented; e.g., at the genome-transcriptome interface, one of the major oligogenic loci involved in conversive spectrum disorders may carry a developmentally sensitive allele in a stable polymorphism (balanced polymorphism) in which the gene expression mechanism is gradually suppressed by pleiotropic androgens especially dehydroxyepiandrosterone sulfate (DHEA-S). Taxonomic implications for the much-needed rapprochement between the forthcoming Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-V) and the International Classification of Diseases (ICD) are discussed

Dental fear, anxiety, and phobia; causes, diagnostic criteria and the medical and social impact

Despite technological advances in modern medical science and practice, many people still associate dental treatment with unpleasant emotional sensations and pain. According to the current literature, dental fear and anxiety are psychological barriers that negatively affect frequency of patient attendance which results in avoidant behavior and poorer oral health-related quality of life. This paper was therefore aimed at discussing basic theoretical aspects concerning diagnostic criteria, causes, and impacts of dental fear, anxiety, and phobia. Clarifying their differential diagnostic characteristics, clinical features and specific causes may play an important role in proper diagnosing, positive influencing, and management of this group of patients, thus providing the opportunity for increasing quality of dental healthcare services as well as improving patient’s dental health and self-perceived quality of life

Compassion and suppression in caregivers: twin masks of tragedy and joy of caring

Background: Compassionate caregiving is a critical skill for workers among the helping professions, but the degree of empathy required by caregivers can place high demands on their mental and emotional resources. While many professionals employ successful coping strategies to mitigate these stressors, others experience compassion fatigue or burnout from emotional exhaustion. The objective of this research was to evaluate the relationships between caregivers’ demographic/career variables, compassion satisfaction, compassion fatigue, and psychodynamic defense mechanisms such as suppression, repressive function, regression in the service of the Ego, and rationalization. Methods: Participants were 250 caregivers with 178 (71,2%) women and 72 men (28,8%) between 18 and 80 years old (Mean age = 41,37; SD = 13,78). Standardized instruments were used to assess compassion in its different meanings (Professional Quality of Life Measure, ProQOL-5) and deployment of defense mechanisms such as suppression (Suppression Mental Questionnaire, SMQ). Correlational analyses were performed. Results: Greater compassion satisfaction was positively associated with more years of study and inversely associated with increasing age and working days per week. Burnout was positively correlated with greater age, more working hours per week, and more working days per week. Higher secondary traumatic stress was associated with increasing age, higher working hours, and more working days per week, while it was inversely associated with more years of study. Regarding the psychological defense mechanisms, more years of study was inversely associated with lower deployment of the repressive function, regression in the service of the Ego, and rationalization. Advancing age was negatively correlated with repression and regression in the service of the Ego, while it was positively correlated with rationalization. A higher number of working days per week was associated with greater utilization of all defense mechanisms, and higher working hours per week was correlated with higher SMQ total scores and greater use of the repressive function. Greater deployment of nearly all defense mechanisms was associated with greater secondary traumatic stress, while compassion satisfaction was associated with less utilization of repression, rationalization, and lower total SMQ scores. Conclusions: Excessive reliance on psychodynamic defense mechanisms can increase caregivers’ risk for burnout or secondary traumatic stress. Compassion satisfaction might serve as one coping strategy to mitigate emotional exhaustion among professionals

DNA methylation of FKBP5 and response to exposure-based psychological therapy

Differential DNA methylation of the HPA-axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences, and may play a role in how well people respond to psychological treatments. Participants (n=111) received exposure-based CBT for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (β=-4.26, p=3.90x10-4), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p=0.045), but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences

Pyrogenic Cytokines Mediated Pathophysiology of Fever and Role of Mefenamic Acid in Pediatric Practice

While fever in most cases represents a normal physiological response to illness, many times it is a presenting sign of a more serious underlying condition. Hence, it is important to assess a child who may be suffering with a serious condition and may require treatment in terms of antipyretic agents. The use of antipyretic agents is usually guided by the degree of fever, and the discomfort caused by fever and associated pain. Paracetamol and, more recently, ibuprofen are the generally used over-the-counter drugs for antipyresis. However, of late, there is a trend of increased use of mefenamic acid as antipyretic. Mefenamic acid has shown better efficacy and tolerability as compared to the other nonsteroidal anti-inflammatory drugs (NSAIDs) in use. In this review, authors have assessed the existing literature on the role of mefenamic acid in pediatric fever. They have highlighted the role of mefenamic acid in pediatric febrile illness in terms of clinical uses, efficacy, comparison with other NSAIDs and its safety in pediatric patients. Its probable action in inflammatory fever and febrile seizure due to its inhibitory action on the NLRP3 inflammasome and potential antiviral actions in viral infections are also highlighted, respectively

The Journal of Undergraduate Research: Volume 06

This is the complete issue of the South Dakota State University Journal of Undergraduate Research, Volume 6

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 144

This bibliography lists 257 reports, articles, and other documents introduced into the NASA scientific and technical information system in July 1975

Complications Associated with Local Anesthesia in Oral and Maxillofacial Surgery

One of the important attempts in clinical oral surgery practice is to maintain safe and effective local anesthesia. Dental procedures are frequently performed under local anesthesia; thus, drug-related complications are often encountered. It is mandatory to have a preoperative evaluation of the patient and choosing the proper local anesthetic agent. Various complications including hypersensitivity, allergy, overdosage, toxicity, hematoma, trismus, paresthesia, or neuralgia can be observed during practice. Therefore, the practitioner should be aware of the possible complications and management methods. The aim of this chapter is to review the preoperative and postoperative complications associated with the local anesthetic in oral and maxillofacial surgery practice. The prevention of measures and treatment of the complications is also emphasized