The 712A/G polymorphism of Brain-derived neurotrophic factor is associated with Parkinson's disease but not Major Depressive Disorder in a Chinese Han population

Background: Overlaps in clinical, pathological and molecular characteristics of Parkinson’s disease (PD) and Major Depressive Disorder (MD-D) have promoted association studies in search of common genetic risk factors that may predispose or modify this spectrum of disorders. Experimental and clinical data suggest that genetic variations in Brain-derived neurotrophic factor (BDNF) gene may increase the risk for PD and MD-D. Methods: Two hundred and sixty-six PD, 83 MD-D and 400 controls were recruited for this study, assessed using a battery of neuropsychological tests, and genotyped for 11757C/G, 712A/G, 196A/G, and 270C/T in BDNF gene. Results: 712A/G was associated with 2.50-fold time risk of PD. By combining genotypes AG/AA with 712 GG genotype as reference (OR = 1) in stratification analysis, AG/AA genotypes were associated with PD (OR = 2.94, 95% CI = 1.88–4.61). Accordingly, the A allele was significantly overrepresented in PD compared with the G allele (OR = 3.16, 95% CI = 2.08–4.81). This distribution in females and males were similar. Conclusion: Our results suggested a novel association between BDNF 712A/G AG/AA genotypes and PD in a Chinese Han population.     

Post-traumatic Stress Disorder in children and adolescents: from Sigmund Freud's "trauma" to psychopathology and the (Dys)metabolic syndrome.

Post-traumatic Stress Disorder (PTSD) is an anxiety syndrome that develops after exposure to traumatic life events. Symptoms include re-experience of the initial trauma, avoidance of stimuli associated with the trauma and symptoms of excessive arousal. Neuroendocrine studies in adults with PTSD have demonstrated that basal cerebrospinal fluid (CSF) CRH levels are elevated and urinary cortisol levels are variable--low in the majority of cases--whereas other studies demonstrate no differences in urinary and plasma cortisol concentrations. Urinary catecholamine excretion is higher in PTSD patients than those of control subjects and other psychiatric disorders. Children may differ from adults in their psychologic and physiologic responses to severe stressors. Also, exposure to stress during critical periods of development may have irreversible effects on behavioral maturation and may affect specific vulnerable brain areas, altering CNS development. Similar to findings in adult studies, PTSD in children is characterized by increased sympathetic nervous system (SNS) activity, as indicated by elevated norepinephrine levels in the periphery. High cortisol levels in urine or saliva have been reported in most studies of childhood PTSD, while prospective longitudinal studies concerning the natural history of neuroendocrine changes in pediatric PTSD after an acute stressor are limited. The identification of neurobiologic changes in response to early adverse experiences is of major importance for the prognosis, prevention, management, and treatment of children and adolescents at risk for or suffering from PTSD.     

Genetic studies in children with intellectual disability and autistic spectrum of disorders

Autism is one of the five disorders that falls under the umbrella of Pervasive Developmental Disorders (PDD) or Autism Spectrum Disorder (ASD), a category of neurological disorders characterized by "severe and pervasive impairment in several areas of development." ASD is characterized by varying degrees of impairment in communication skills, social interaction and restricted, repetitive stereotyped patterns of behavior. The five disorders under PDD are autistic disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder and PDD-not otherwise specified. ASD can often be reliably detected by the age of 3 years and, in some cases, as early as 18 months. The appearance of any warning signs of ASD is reason to have the child evaluated by a professional specializing in these disorders.     

Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder

Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception).Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate).We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.     

Body Dysmorphic Disorder: Contraindication or Ethical Justification for Female Genital Cosmetic Surgery in Adolescents

Is Female Genital Cosmetic Surgery for an adolescent with Body Dysmorphic Disorder ever ethically justified? Cosmetic genital surgery (specifically labioplasty) for adolescent girls is one of the most ethically controversial forms of cosmetic surgery and Body Dysmorphic Disorder is typically seen as a contraindication for cosmetic surgery. Two key ethical concerns are (1) that Body Dysmorphic Disorder undermines whatever capacity for autonomy the adolescent has; and (2) even if there is valid parental consent, the presence of Body Dysmorphic Disorder means that cosmetic surgery will fail in its aims. In this article, we challenge, in an evidence‐based way, the standard view that Body Dysmorphic Disorder is a contraindication for genital cosmetic surgery in adolescents. Our argument gathers together and unifies a substantial amount of disparate research in the context of an ethical argument. We focus on empirical questions about benefit and harm, because these are ethically significant. Answers to these questions affect the answer to the ethical question. We question the claim that there would be no benefit from surgery in this situation, and we consider possible harms that might be done if treatment is refused. For an adolescent with Body Dysmorphic Disorder, the most important thing may be to avoid harm. We find ourselves arguing for the ethical justifiability of cosmetic labioplasty for an adolescent with Body Dysmorphic Disorder, even though we recognize that it is a counter intuitive position. We explain how we reached our conclusion.     

Avoidant Personality Disorder versus Social Phobia: The Significance of Childhood Neglect

Objectives

Avoidant personality disorder (AvPD) and social phobia (SP) are common disorders both in the community and in clinical settings. Whether the two disorders represent different severity levels of social anxiety disorder is currently in dispute. The relationship between AvPD and SP is probably more complex than previously assumed. Several environmental, temperamental, and constitutional factors may play a role in the etiology of AvPD and SP. Better knowledge about childhood experiences may shed light on similarities and differences between the two disorders. The aim of this study was to compare self-reported childhood experiences in AvPD and SP patients.

Design

This is a cross-sectional multi-site study of 91 adult patients with AvPD and/ or SP. We compared patients with AvPD with and without SP (AvPD group) to patients with SP without AvPD (SP group).

Methods

The patients were examined using structured diagnostic interviews and self-report measures, including Child Trauma Questionnaire, Parental Bonding Instrument, and Adult Temperament Questionnaire.

Results

Both AvPD and SP were associated with negative childhood experiences. AvPD patients reported more severe childhood neglect than patients with SP, most pronounced for physical neglect. The difference between the disorders in neglect remained significant after controlling for temperamental factors and concurrent abuse.

Conclusions

The study indicates that childhood neglect is a risk factor for AvPD and may be one contributing factor to phenomenological differences between AvPD and SP.     

A systems biological study on the comorbidity of autism spectrum disorders and bipolar disorder

Autism Spectrum Disorder (ASD) is a "spectrum" of disorders, characterized by varying degrees of symptoms ranging from mild to severe. Among Psychiatric disorders, Autism Spectrum Disorders have the strongest evidence for a genetic basis, yet the search for specific genes contributing to these often devastating developmental syndromes has proven extraordinarily difficult. Bipolar Disorder (BP) is a manic-depressive disorder whose symptoms are characterized by extremities in moods. It is also called as the "Mood disorder". BP, like, ASD also has a strong genetic basis and identification of the candidate genes still remains an ongoing effort. Literature studies point to the hypothesis that ASD and BP have good chances of comorbidity and that they may share common pathways for their manifestation. But this hypothesis has not been worked on in depth. Thus, the study focuses on identifying the chances of their comorbidity by identifying their common pathways and the genes involved in the pathways and also discuss the degree of chances of their comorbidity based on the genes involved in the common pathways. Networks for the genes are also constructed to represent their commonness or uniqueness for the disorders.     

全球变化影响下的生态系统风险的相关理论及联系

全球变化深刻影响着全球生态系统,全球变化胁迫超过一定程度则会导致生态系统恢复力下降,极端事件频发,从而使生态系统服务功能退化甚至丧失.量化全球变化的风险,进而制定恰当的人为适应策略是目前应对全球变化的重要途径.全球变化可能降低生态系统的恢复力,从而导致生态系统脆弱性升高,引发生态系统退化风险.目前,相关研究多依托基于星...     

Influence of Timed Nutrient Diet on Depression and Light Sensitivity in Seasonal Affective Disorder

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall‐winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO‐rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO‐ or protein‐rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM‐IV‐diagnosed depressed women with SAD (n=22, 19–63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating ～1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH‐SAD (with 21‐item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21‐HDRS score (mean±SD) decreased from 19.6±6.4 to 14.4±7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.     

Metabolomics in Schizophrenia and Major Depressive Disorder

Defining pathophenotype, a systems level consequence of a disease genotype, together with environmental and stochastic influences, is an arduous task in psychiatry. It is also an appealing goal, given growing need for appreciation of brain disorders biological complexity, aspiration for diagnostic tests development and ambition to identify novel drug targets. Here, we focus on the Schizophrenia and Major Depressive Disorder and highlight recent advances in metabolomics research. As a systems biology tool, metabolomics holds a promise to take part in elucidating interactions between genes and environment, in complex behavioral traits and psychopathology risk translational research.     

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma,cholangiocarcinoma and hepatocellular carcinoma

The NOTCH signalling pathway is one of the key molecular pathways of embryonic development and adult tissues homeostasis in mammals. Mammals have four NOTCH receptors and various ligands that modulate their activity. Many cell disorders, whose genesis involves the NOTCH signalling pathway, have been discovered, including cancer. The mechanisms by which these receptors and their ligands affect liver cell transformation are not yet well understood, and they seem to behave as both oncogenes and tumour‐suppressor proteins. In this review, we discuss the published data regarding the role of these proteins in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma malignancies. The alteration of the NOTCH signalling pathway may be one of the main drivers of hepatic neoplastic growth. However, this signalling pathway might also modulate the development of specific liver tumour features. The complexity of the function of NOTCH receptors and their ligands may be due to their interactions with many other cell signalling pathways. Furthermore, the different levels of expression and activation of these receptors could be a reason for their distinct and sometimes contradictory effects.     

War and Bereavement: Consequences for Mental and Physical Distress

Background

Little is known about the long-term impact of the killing of a parent in childhood or adolescence during war on distress and disability in young adulthood. This study assessed current prevalence rates of mental disorders and levels of dysfunction among young adults who had lost their father due to war-related violence in childhood or adolescence.

Methods

179 bereaved young adults and 175 non-bereaved young adults were interviewed a decade after experiencing the war in Kosovo. Prevalence rates of Major Depressive Episode (MDE), anxiety, and substance use disorders, and current suicide risk were assessed using the Mini–International Neuropsychiatric Interview. The syndrome of Prolonged Grief Disorder (PGD) was assessed with the Prolonged Grief Disorder Interview (PG-13). Somatic symptoms were measured with the Patient Health Questionnaire. General health distress was assessed with the General Health Questionnaire.

Findings

Bereaved participants were significantly more likely to suffer from either MDE or any anxiety disorder than non-bereaved participants (58.7% vs. 40%). Among bereaved participants, 39.7% met criteria for Post-Traumatic Stress Disorder, 34.6% for PGD, and 22.3% for MDE. Bereaved participants with PGD were more likely to suffer from MDE, any anxiety disorder, or current suicide risk than bereaved participants without PGD. Furthermore, these participants reported significantly greater physical distress than bereaved participants without PGD.

Conclusion

War-related loss during middle childhood and adolescence presents significant risk for adverse mental health and dysfunction in young adulthood in addition to exposure to other war-related traumatic events. Furthermore, the syndrome of PGD can help to identify those with the greatest degree of distress and dysfunction.     

Time Domain Analysis of Heart Rate Variability Signals in Valence Recognition for Children with Autism Spectrum Disorder (ASD)

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental condition that is characterized by various social impairments. Children with ASD have major difficulties in expressing themselves, resulting in stress and meltdowns. Understanding their hidden feelings and needs may help in tackling and avoiding such strenuous behaviors.ObjectiveThis research aims to aid the parents and caretakers of children with ASD to understand the hidden and unexpressed emotional state by using physiological signals obtained from wearable devices.MethodsHere, electrocardiogram (ECG) signals pertaining to two valence states (‘like’ and ‘dislike’) were recorded from twenty children (10 Control and 10 children with ASD). The heart rate variability (HRV) signals were then obtained from the ECG signals using the Pan-Tompkins's algorithm. The statistical, higher order statistics (HOS) and geometrical features which were statistically significant were trained using the K Nearest Neighbor (KNN) and Ensemble Classifier algorithms.ResultsThe findings of our analysis indicate that the integration of major statistical features resulted in an overall average accuracy of 84.8% and 75.3% using HRV data for the control and test population, respectively. Similarly, geometrical features resulted in a maximum average accuracy of 84.8% and 74.2% for control and test population respectively. The decreased HRV in the test population indicates the presence of autonomic dysregulation in children with ASD when compared to their control peers.     

Endophenotypes as a measure of suicidality

Suicide is thought to result from the harmful interaction of multiple factors that have social, environmental, neurobiological, and genetic backgrounds. Recent studies have suggested that genetic predisposition to suicidal behavior may be independent of the risk of suicide associated to mental disorders, such as affective disorders, schizophrenia, or alcohol dependence. Given the suicidal behavior heterogeneity and its hereditary complexity, the need to find demonstrable intermediate phenotypes that may make it possible to establish links between genes and suicide behaviors (endophenotypes) seems to be necessary. The main objective of this review was to consider the candidate endophenotypes of suicidal behaviors. Due to the recent advances in neuroimaging, we also characterize brain regions implicated in vulnerability to suicide behavior that are influenced by gene polymorphisms associated with suicidal behavior.     

Obsessive-Compulsive Disorder and Autism Spectrum Disorders: Longitudinal and Offspring Risk

Background

Despite substantial similarities and overlaps in the pathophysiology of obsessive-compulsive disorders (OCD) and autism spectrum disorders, little is known about the clinical and etiologic cohesion of these two disorders. We therefore aimed to determine the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders.

Methods

In a prospective study design we explored the effect of a prior diagnosis of OCD in patients and parents on the susceptibility to autism spectrum disorders and vice versa. Analyses were adjusted for sex, age, calendar year, parental age and place at residence at time of birth. As measures of relative risk incidence rate ratios (IRR) and accompanying 95% confidence intervals (CIs) were employed.

Results

The risk of a comorbid diagnosis of OCD in individuals with autism spectrum disorder and aggregation of autism spectrum disorders in offspring of parents with OCD were increased. Individuals first diagnosed with autism spectrum disorders had a 2-fold higher risk of a later diagnosis of OCD (IRR = 2.18, 95% CI = 1.91–2.48), whereas individuals diagnosed with OCD displayed a nearly 4-fold higher risk to be diagnosed with autism spectrum disorders (IRR = 3.91, 95% CI = 3.46–4.40) later in life. The observed associations were somewhat stronger for less severe types of autism spectrum disorders without a comorbid diagnosis of mental disabilities.

Conclusions

The high comorbidity, sequential risk, and shared familial risks between OCD and autism spectrum disorders are suggestive of partially shared etiological mechanisms. The results have implications for current gene-searching efforts and for clinical practice.     

Inhibition in Adults with Attention Deficit/Hyperactivity Disorder: Event-Related Potentials in the Stop Task

The core deficit in Attention Deficit/Hyperactivity Disorder (ADHD) may be a deficiency in executive functions, particularly the processes that are associated with the inhibition of predominant responses. To test this notion in the adult population, healthy undergraduate volunteers and students with ADHD symptoms performed a visual Stop Signal Task (Logan et al. J Exp Psychol: Hum Percept Perform 10:276–291, 1984) while Event-Related brain Potentials were recorded. The two groups did not differ on behavioral measures of performance, but there was a significant difference in the N2–P3 component. These results underline the robustness of an N2–P3 difference between healthy adults and people with ADHD symptoms that have persisted into young adulthood.     

Psychophysiological markers of vulnerability to psychopathology in men with an extra X chromosome (XXY)

Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY) is one of the most common sex chromosomal aneuploidies (1 in 650 male births) and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three "classic" psychophysiological markers of psychosis in Klinefelter syndrome (KS): smooth pursuit eye movements (SPEM), prepulse inhibition (PPI) and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control) as well as PPI and P50 suppression (reflecting sensory gating) were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI) (effect size 1.6). No abnormalities were found in suppression of the P50 (effect size 0.6). We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into "at risk" pathways to psychopathology.