Brain reward circuitry:The overlapping neurobiology of trauma and substance use disorders

Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community samples.The possibility of a shared aetiology remains an important question in translational neuroscience.Advancements in genetics,basic science,and neuroimaging have led to an improved understanding of the neural basis of these disorders,their frequent comorbidity and high rates of relapse remain a clinical challenge.This project aimed to conduct a review of the field’s current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD.A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders,and is summarized in detail,including evidence from both animal and clinical studies.Upon summarizing the relevant literature,this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues.It provides an overview of brain reward circuitry and its relation to the neurobiology,symptomology,and phenomenology of trauma and substance use.This review provides clinical insights and implications of the proposed theory,including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology.Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.

Attachment Styles and Traumatic Responses: Exploring the Impact of Parental Interaction on Child Development and Coping Mechanisms

This article explores the intricate relationship between attachment styles formed during early childhood and the subsequent responses to traumatic events, particularly the death of a parent. Drawing on the theoretical framework of attachment theory and incorporating contemporary research, the paper discusses how parental interactions shape the neural circuitry of infants and children, influencing their ability to form secure or insecure attachments. These attachment styles, in turn, play a critical role in determining the child’s coping mechanisms when faced with trauma. This paper focuses on trying to understand how attachment theory is connected to the reaction to trauma with a highlight on the four major styles of attachments which are secure, anxious, avoidant, and disorganized to mention but a few, and how they influence stress and adversity in children. Attachment theory holds that human beings’ ability to form affectional bonds in infancy determines their patterns of relatedness across the life cycle. The type of attachment that is secure usually supports healthy adaptation and good coping mechanisms regardless of the trauma in the childhood of the child. While secure attachment mostly facilitates favorable trauma-related outcomes, anxious or avoidant attachment can exacerbate or alter the responses. The caregiving system that is avoidant attachment has implications of autonomous self-functioning which has features of suppression of the emotional response and poor search for emotional support during stress. From the principles of developmental psychology and trauma theory, the paper also focuses on the major significance of the child’s early caregivers’ interactions that define the resilience and vulnerability factor. This knowledge is therefore critical in designing specific interventions based on the improvement of coping behaviors and emotional regulatory systems of children who have been exposed to trauma. Finally, we have the synthesis of new knowledge about the role of secure attachment relationships as its fundamental element in shaping adaptive traumatization and psychological development. The article also delves into the physiological processes involved in emotional regulation and the role of cortisol in disrupting attachment. Finally, the implications of these findings for therapeutic interventions and the challenges of addressing prolonged grief and traumatic responses in clinical settings are considered.

Translational bioengineering strategies for peripheral nerve regeneration:opportunities,challenges,and novel concepts

Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.

Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica

In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanfi （ST36） and Yanglingquan （GB34）. In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold （paw withdrawal latency） was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanfi and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.

The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.

High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells.Therefore,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities.On gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours.The offspring were weaned at 28 days and subjected to the Morris water maze test.The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day（P） 0,14 and 28.Vascular endothelial growth factor（VEGF） and phosphoinositide 3-kinase（PI3 K）/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay.Exposure to high-concentration（3.5%） sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing times.At 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling（TUNEL）-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring.At 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT（p-AKT） levels were decreased in the fetal brain.These changes were not observed in animals given low-concentration（2%） sevoflurane exposure.Together,our findings indicate that exposure to a high concentration of sevoflurane（3.5%） in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring.

Preparation of rabbit anti-rat LRRN3 polyclonal antibody and study of its expression

BACKGROUND： Studies have shown that the Repeat superfamily, could be related to neural LRRN3, a member of the Neuron Leucine-Rich development, differentiation, information transmission, and other functions, but most studies have focused on nucleic acid levels and few have reported on LRRN3 protein levels. OBJECTIVE： To prepare rabbit anti-rat LRRN3 polyclonal antibody and to observe protein tissue expression profiles. DESIGN, TIME AND SEI-rlNG： In vitro, molecular, biological experiments were performed from October 2007 to April 2009 in Laboratory of Neurobiology at Xiangya School of Medicine, Central South University. MATERIALS： Immunization antigen, namely rat MaI-LRRN3C-His recombinant protein, was provided by the Laboratory of Neurobiology at Xiangya School of Medicine, Central South University. METHODS： Rat Mal-LRRN3C-His recombinant protein was used to immunize male, New Zealand rabbits, and rabbit anti-rat LRRN3 polyclonal antibody was prepared. MAIN OUTCOME MEASURES： Antibody purification was conducted using Protein A affinity chromatography, and the LRRN3 anti-serum titer was identified using enzyme-linked immunosorbent assay. Immunohistochemical techniques and Western blot preliminary tests were used to determine LRRN3 protein expression profiles in adult rats. RESULTS： A highly purified rabbit anti-rat LRRN3 polyclonal antibody was obtained. Western Blot results from rat brain total protein revealed a band at 79 kD, which was consistent with the size of LRRN3. Immunohistochemistry results showed that protein was mainly expressed in the central nervous system, and no significant positive signals were observed in other tissues. Positive cells included neurons of cerebral cortex and hippocampal dentate gyrus granule cell layer, and cerebellar Purkinje cells. There was no positive expression in glial cells. CONCLUSION： Rabbit anti-rat LRRN3 polyclonal antibody was successfully prepared at a high purity from the prokaryotic-expressed MaI-LRRN3C-His recombinant protein, which served as an antigen. Rat LRRN3 protein was primarily expressed in cerebral cortex neurons, hippocampal dentate gyrus granule cell layer neurons, and cerebellar Purkinje cells.

Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring

Mild intrauterine hypoperfusion(MIUH)is a serious pathological event that affects the growth and development of fetuses and offspring.MIUH can lead to growth restriction,low birth weight,neurodevelopmental disorders,and other adverse clinical outcomes.To study the effects of MIUH on learning and memory function in offspring,a model of MIUH was established by placing a coil(length 2.5 mm,diameter 0.24 mm)on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17).Next,120 mg/kg lithium chloride(the MIUH+Li group)or normal saline(the MIUH group)was injected intraperitoneally into these rats.In addition,120 mg/kg lithium chloride(the Li group)or normal saline(the SHAM group)was injected intraperitoneally into pregnant rats without coil placement.The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth.In the MIUH group,the escape latency and journey length before reaching the platform were both increased,and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group.Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins)expression was significantly downregulated in the MIUH group compared with the SHAM group.Furthermore,western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats,and revealed that glycogen synthase kinase 3β(GSK3β)expression was upregulated andβ-catenin expression was downregulated in the MIUH group compared with the SHAM group.In addition,compared with the MIUH group,the expression levels of p-GSK3βandβ-catenin were upregulated in the MIUH+Li group.These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3βsignaling pathway.The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018 PS07 K)in June 2018.

Current understanding of the neuropathophysiology of pain in chronic pancreatitis

Chronic pancreatitis(CP) is a chronic inflammatory disease of the pancreas. The main symptom of patients with CP is chronic and severe abdominal pain. However, the pathophysiology of pain in CP remains obscure.Traditionally, researchers believed that the pain was caused by anatomical changes in pancreatic structure. However, treatment outcomes based on such beliefs are considered unsatisfactory. The emerging explanations of pain in CP are trending toward neurobiological theories. This article aims to review current evidence regarding the neuropathophysiology of pain in CP and its potential implications for the development of new treatments for pain in CP.

Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats

Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.

Expression of acetylated histone 3 in the spinal cord and the effect of morphine on inflammatory pain in rats

In this study, a rat model of inflammatory pain was produced by injecting complete Freund’s adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using immunohistochemical staining. One day following injection, there was a dramatic decrease in acetylated histone 3 expression in spinal cord dorsal horn neurons. However, on day 7, expression recovered in adjuvant-injected rats. While acetylated histone 3 labeling was present in dorsal horn neurons, it was more abundant in astrocytes and microglial cells. The recovery of acetylated histone 3 expression was associated with a shift in expression of the protein from neurons to glial cells. Morphine injection significantly upregulated the expression of acetylated histone 3 in spinal cord dorsal horn neurons and glial cells 1 day after injection, especially in astrocytes, preventing the transient downregulation. Our results indicate that inflammatory pain induces a transient downregulation of acetylated histone 3 in the spinal cord dorsal horn at an early stage following adjuvant injection, and that this effect can be reversed by morphine. Thus, the downregulation of acetylated histone 3 may be involved in the development of inflammatory pain.

Understanding the Etiology and Treatment Approaches of Schizophrenia: Theoretical Perspectives and Their Critique

This paper reviewed genetic, neurodevelopmental, and neurobiological perspectives to understand the etiology and relevant treatment approaches of schizophrenia. Although genetic and neurodevelopmental theories provide a substantial contribution to the etiology of schizophrenia, neurobiological one has its dominant stance in which it can explain causative mechanisms of schizophrenia, identify targets for treatment, and predict outcomes well. According to the neurobiology, onset and course of schizophrenia are well supported by the alterations in neurotransmitters such as dopamine or serotonin. Based on this mechanism, antipsychotics have been widely used as one of the treatment approaches for schizophrenia. By following up the degree of patients’ responses to antipsychotics, treatment outcomes could be evaluated or predicted. Although neurobiology seldom provides information about identification or prevention of risk factors about schizophrenia compared to genetic and neurodevelopmental approaches, it has well-established scientific foundations, ability to guide treatment, applicability across age and culture, and usefulness as a research framework.

Fractal description and quantitative analysis of normal brain development in infants

We examined the fractal pattern of cerebral computerized tomography images in 158 normal infants aged 0 3 years, based on the quantitative analysis of chaotic theory. Results showed that the fractal dimension of cerebral computerized tomography images in normal infants remained stable from 1.86-1.91. The normal distribution range in the neonatal period, 1-2 months old infants, 1-2 year old infants, and of 2-3 year old infants was 1.88 1.90 （mean： 1.891 3 ± 0.006 4）, 1.89-1.90 （mean： 1.892 7 ±0.004 5）, 1.86-1.90 （mean： 1.886 3 ± 0.008 5）, and 1.88-1.91 （mean： 1.895 8±0.008 3）, respectively. The spectrum width of the multifractal spectrum （△α） in normal infants was 1.4618. These data suggest that the spectral width parameters of the multifractal spectrum and the fractal dimension criteria in normal children may be useful as a practical specific parameter for assessing the fractal mode of brain development in normal infants.

Tumor necrosis factor-alpha in experimental autoimmune neuritis

Tumor necrosis factor-α （TNF-α） plays a key role in the pathogenesis of experimental autoimmune neuritis （EAN） as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.

N-methyl-D-aspartate receptor subtype 3A promotes apoptosis in developing mouse brain exposed to hyperoxia

In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling （TUNEL）/neuron-specific nuclear protein （NeuN） and 5-bromo-2＇-deoxyuridine （BrdU）/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL＋/NeuN＋ and BrdU＋/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.

Cyclic patterns of incidence rate for skin malignant melanoma:association with heliogeophysical activity

Background： Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma （SMM; ICD9, Dx： 172） in the Czech Republic （period T=7.50～7.63 years）, UK （T= 11.00 years） and Bulgaria （T= 12.20 years）. Incidences com- pared with the sunspot index Rz （lag-period dT=＋2, ＋4, ＋6, ＋ 10 or ＋ 12 years） have indicated that maximal rates are most likely to appear on descending slopes of the ;ll-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity （HGA） components exhibiting similar cyclicity. Methods： Annual incidences of SMM from 5 countries （Czech Republic, UK, Bulgaria, USA and Canada） over various time spans during the years 1964-1992 were analyzed and their correlations with cyclic Rz （sunspot number） and aa （planetary geomagnetic activity） indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results： Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA （T=8.63 years, P〈0.05） and Canada （Ontario, T=9.91 years, P〈0.10）. Also, various ＇hypercycles＇ were established （T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively） describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz （dT=＋6 and ＋7 years, respectively） and aa （dT=-10 and ＋9 years, respectively） was described. Possible interactions of cyclic non-photic influences （UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations） with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion： The above findings on cyclicity and temporal association of SMM with cyclic environmental factors could not only allow for better forecasting models but also lead to a better understanding of melanoma aetiology.

Neurobiological mechanisms underlying delayed expression of posttraumatic stress disorder:A scoping review

BACKGROUND The capacity of posttraumatic stress disorder(PTSD)to occur with delayed onset has been documented in several systematic reviews and meta-analyses.Neurobiological models of PTSD may provide insight into the mechanisms underlying the progressive increase in PTSD symptoms over time as well as into occasional occurrences of long-delayed PTSD with few prodromal symptoms.AIM To obtain an overview of key concepts explaining and types of evidence supporting neurobiological underpinnings of delayed PTSD.METHODS A scoping review of studies reporting neurobiological findings relevant to delayed PTSD was performed,which included 38 studies in the qualitative synthesis.RESULTS Neurobiological mechanisms underlying PTSD symptoms,onset,and course involve several interconnected systems.Neural mechanisms involve the neurocircuitry of fear,comprising several structures,such as the hippocampus,amygdala,and prefrontal cortex,that are amenable to time-dependent increases in activity through sensitization and kindling.Neural network models explain generalization of the fear response.Neuroendocrine mechanisms consist of autonomic nervous system and hypothalamic-pituitary-adrenocortical axis responses,both of which may be involved in sensitization to stress.Neuroinflammatory mechanisms are characterized by immune activation,which is sometimes due to the effects of traumatic brain injury.Finally,neurobehavioral/contextual mechanisms involve the effects of intervening stressors and mental and physical disorder comorbidities,and these may be particularly relevant in cases of long-delayed PTSD.CONCLUSION Thus,delayed PTSD may result from multiple underlying neurobiological mechanisms that may influence the likelihood of developing prodromal symptoms preceding the onset of full-blown PTSD.

Biochemical and Neurobiological Study of Moroccan Autists

Autism spectrum disorder (ASD) is a range of complex neurodevelopment disorders, characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. Its diagnosis is very difficult and consists of only clinical criteria. The aim of this study is to confirm autism disorder, among three children (2 girls and 1 boy), recruited in a social association of children in a precarious situation, located in Rabat, Morocco, and to evaluate some biological and neurobiological parameters among these children. The confirmation of autistic status is realized using Questionnaire (E2) and the evaluation of biological parameters (organic acids, urinary peptides, toxic metals and essential elements) is done in urine and hair of these children. Obtained children’s scores of E2 Questionnaire, is found in the favor of autism. Moreover, abnormal levels of urinary organic acids, urinary peptides, toxic and essential metals are observed.

Biological Trajectory for Psychosocial Risk Factors in Psychiatric Disorders—A Concept Based Review

Current understanding of mental disorders is based upon “biopsychosocial model”. Research also suggests what biological changes take place in a particular disorder as well as nature of risk which arises from psychological, social and environmental conditions. However it remains unclear how these psychosocial and environmental risk factors interact with biological factors which lead to clinical syndromes. This paper examines interrelationship of psychosocial and environmental risk and biological changes observed in mental disorders and tries to identify the possibility of a pathway of the psychopathology of psychiatric disorders. The review aims to demonstrate that significant advances in the fields of psychosocial, cultural, anthropological and neurobiological research provide novel insights into the etiology of mental disorders. There are neurochemical, functional and structural neurobiological, neurocognitive, immunological findings and findings from gene-environment interaction that appears promising. However these findings are in an isolated manner. Comprehensive studies examining major biological changes together in relation to psychosocial risk factors are lacking. Every individual reacts differently to the same environmental risk while there tends to be similarities in individual outcome in response to such stressors. The findings though robust independently, remain very preliminary to suggest a sequential trajectory for developing a clear pathway for pathogenesis. It is currently unclear whether there is a differential psychopathological impact of psychosocial stressors in different cultures despite the extensive variability both between and within major social groups and societies. Further research investigating modifiable and non-modifiable risk factors in context of prevailing socio-economic conditions is urgently needed to plan effective interventions.

Autism Spectrum Disorder:The Dilemma of Untimely Recognition,Intervention and Diagnostic Scales Obtainable at Indian Sub-continent

The increasing prevalence of Autism Spectrum Disorder makes it as considerable issue worldwide.Recent studies addresses the hot topic of Mirror Neuronal System(MNS)confers behind the ASD.However,the cause is uncertain,Indian population prone to varied prenatal and postnatal factors of the condition.Indian parents and professional still be at the initial awareness phase of the spectrum.Years of delay in identification and intervention while comparing with world standards due to various Indian socio-economic and socio-cultural factors.Less availability of screening and diagnostic tools headed to relay on culturally irrelevant and expensive international tools.Government funded research initiatives developed ISAA,INDT-ASD,CASI and AIIMS Modified INDT-ASD as culturally relevant indigenous tools and available on practice.So far,the tools have their own advantages and limitations,requires further research and progression.Owing to scarcity of trained professionals for a wide population range,home based parent-mediated therapies be the most preferred mode of therapy.However,the therapeutic options vary with people.The study aimed to ascertain the present Indian scenario,look upon the awareness about the condition,availability of screening and diagnostic facilities,the early identification and timely intervention program.In addition,the study briefly confers the biological and clinical background of ASD.