Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome.

Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical areas implicated in psychosis, the dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuron-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-Lys4 (H3K4me3) and H3-acetyl-Lys27 (H3K27ac). Differences between neuronal and neuron-depleted chromatin states were the major axis of variation in histone modification profiles, followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci were identified in neuronal and neuron-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly over-represented in neuronal H3K4me3 and H3K27ac landscapes. Our Resource, sponsored by PsychENCODE and CommonMind, highlights the critical role of cell-type-specific signatures at regulatory and disease-associated noncoding sequences in the human frontal lobe.

Grupos de alta para pacientes con distimia crónica: una propuesta psicoterapéutica orientada al fin de tratamiento / Groups of discharge for patients with chronic distimia: a psychotherapeutic proposal orientated to the end of treatment

La intención del autor en este artículo es reflexionar desde la teoría psicoanalítica y desde la experiencia clínica y proponer un planteamiento terapéutico para los pacientes con distimia crónica resistente a los tratamientos. Este trabajo incluye las siguientes formulaciones 1- Los pacientes tratados durante mucho tiempo en las Unidades de Salud Mental Comunitarias y que se cronifican en sus mecanismos patogénicos han de tener una ineludible fecha final de tratamiento 2- Se justifica la psicoterapia de grupo como una posible última fase de su tratamiento en salud mental 3- Se hace la hipótesis de que el alta mejorará la posición de resistencia al cambio psicológico. En este recorrido se revisan los textos freudianos Análisis Terminable e Interminable, Más Allá del Principio de Placer y el concepto de Técnica Activa propuesto por Ferenczi. A lo largo del artículo se presenta el diseño de los tres grupos terapéuticos realizados, la metodología seguida, los resultados obtenidos, las conclusiones y las preguntas finales (AU)

The intention of the author in this article is to think from the psychoanalytic theory and from the clinical experience. and propose a therapeutic plan for patients with distimia chronicle resistants to the treatments. This work includes the following formulations: 1-The patients treated for a long time in the Community Mental Health Units who become chronic in their pathogenic mechanisms have to have an unavoidable final date of treatment 2-we justify the group psychotherapy itself as a last possible phase of the treatment 3- it’s done the hypothesis that the discharge will improve the position of resistance to a psychological change. We review the Freudian texts: Analysis Terminable and Interminable, Beyond the Pleasure Principle and the concept 'active technique' proposed by Ferenczi. Along the article it is presented the design of the three group psychotherapies done, the followed methodology, the obtained results, the conclusions and the final questions (AU)

Regional gray matter volume and anxiety-related traits interact to predict somatic complaints in a non-clinical sample.

Somatic complaints can be important features of an individual's expression of anxiety. Anxiety-related traits are also risk factors for somatic symptoms. However, it is not known which neuroanatomical mechanisms may be responsible for this relationship. In this study, our first step was to use voxel-based morphometry (VBM) approaches to investigate the neuroanatomical basis underlying somatic complaints in a large sample of healthy subjects. We found a significant positive correlation between somatic complaints and parahippocampal gyrus (PHG) volume adjacent to the entorhinal cortex. Further analysis revealed that the interaction between PHG volume/entorhinal cortex and neuroticism-anxiety (N-Anx) predicted somatic complaints. Specifically, somatic complaints were associated with higher N-Anx for individuals with increased PHG volume. These findings suggest that increased PHG volume and higher trait anxiety can predict vulnerability to somatic complaints in the general population.

Comentario al trabajo de Alessandra Lemma "El psicoanálisis en tiempos de la tecnocultura: algunas reflexiones sobre el destino del cuerpo en el espacio virtual" / No disponible

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Pathological gambling: update on decision making and neuro-functional studies in clinical samples.

Given the importance and the burden of pathological gambling (PG) and its effect on gamblers and their relatives, better comprehension of the phenomena involved in its development and persistence is needed. The present paper describes the previous 5 years of studies on decision making and magnetic resonance imaging in people with PG. Twenty-six studies (456 participants with PG) were included. Perseveration in monetary tasks was associated with PG despite intact executive planning abilities. PG was linked with impairment in decision making under uncertainty. Hyperactivation of the reward pathway was repeatedly found. PG was also linked with neural hyperactivation of the reward pathway during high-risk conditions and hypoactivation in low-risk conditions. Furthermore, in PG, near misses activated the brain regions related to wins. Numerous similarities were found between PG and substance use disorders, highlighting the scientific basis of the recent reclassification of PG in the spectrum of addictive disorders.

Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders.

Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.

The five factors of personality and regional cortical variability in the Baltimore longitudinal study of aging.

Although personality changes have been associated with brain lesions and atrophy caused by neurodegenerative diseases and aging, neuroanatomical correlates of personality in healthy individuals and their stability over time have received relatively little investigation. In this study, we explored regional gray matter (GM) volumetric associations of the five-factor model of personality. Eighty-seven healthy older adults took the NEO Personality Inventory and had brain MRI at two time points 2 years apart. We performed GM segmentation followed by regional analysis of volumes examined in normalized space map creation and voxel based morphometry-type statistical inference in SPM8. We created a regression model including all five factors and important covariates. Next, a conjunction analysis identified associations between personality scores and GM volumes that were replicable across time, also using cluster-level Family-Wise-Error correction. Larger right orbitofrontal and dorsolateral prefrontal cortices and rolandic operculum were associated with lower Neuroticism; larger left temporal, dorsolateral prefrontal, and anterior cingulate cortices with higher Extraversion; larger right frontopolar and smaller orbitofrontal and insular cortices with higher Openness; larger right orbitofrontal cortex with higher Agreeableness; larger dorsolateral prefrontal and smaller frontopolar cortices with higher Conscientiousness. In summary, distinct personality traits were associated with stable individual differences in GM volumes. As expected for higher-order traits, regions performing a large number of cognitive and affective functions were implicated. Our findings highlight personality-related variation that may be related to individual differences in brain structure that merit additional attention in neuroimaging research.

[Role of various risk factors in the development and diagnosis of recurrent pain in adolescents--students of cadet corps].

Randomized single-blind case--control study is performed. In total, the cadet corp students with recurrent functional abdominal pain and headaches are examined. The paper shows the role of various risk factors in the occurrence of these states. Diagnostic validity is evaluated. Multifactorial genesis of the studied pathology is proved. The essential role in the formation of the psychological characteristics of personality, neurotic states and autonomic dysfunction is shown. Several constitutional characteristics of the organism were not diagnostically significant.

[Comorbide somatic pathology in servicemen with neurotic disorders].

Prevalence and structure of comorbidity a somatic pathology in military men with neurotic disorders was studied. It was established that 40,4% of surveyed noted concomitant somatic pathology, the structure of which was dominated by gastro-intestinal tract (26,8%), and pathology of the cardiovascular system (21,6%). It is shown that concomitant somatic pathology provided aggravating effect on clinic neurotic disorders in serviceman, making it difficult to diagnose mental disorders. The greatest risk concomitant a somatic pathology was marked in patients with depressive and somatoform disorders. Indicates the need for specialized standards of care for persons with comorbid mental and somatic disorders.

The cerebellum link to neuroticism: a volumetric MRI association study in healthy volunteers.

Prior research suggests an association between reduced cerebellar volumes and symptoms of depression and anxiety in patients with mood disorders. However, whether a smaller volume in itself reflects a neuroanatomical correlate for increased susceptibility to develop mood disorders remains unclear. The aim of the present study was to examine the relationship between cerebellar volume and neurotic personality traits in a non-clinical subject sample. 3T Structural magnetic resonance imaging scans were acquired, and trait depression and anxiety scales of the revised NEO personality inventory were assessed in thirty-eight healthy right-handed volunteers. Results showed that cerebellar volume corrected for total brain volume was inversely associated with depressive and anxiety-related personality traits. Cerebellar gray and white matter contributed equally to the observed associations. Our findings extend earlier clinical observations by showing that cerebellar volume covaries with neurotic personality traits in healthy volunteers. The results may point towards a possible role of the cerebellum in the vulnerability to experience negative affect. In conclusion, cerebellar volumes may constitute a clinico-neuroanatomical correlate for the development of depression- and anxiety-related symptoms.

[Peculiarities of clinical manifestations in children with the irritable bowel syndrome].

The article is devoted to the problem of clinical manifestation of irritated bowels syndrome among children. It is stated that the leading symptom of suffering - abdominal pian - is combined with the psychopathologic symptomatology such as various neurosis-like disorders, which should be taken into consideration while developing therapeutic measures among such patients.

Serotonin receptors of type 6 (5-HT6): what can we expect from them?

The serotonin (5-HT) receptors of type 6 (5-HT6) are relatively new. They are quite different from all other 5-HT receptors, as they are characterized by a short third cytoplasmatic loop and a long C-terminal tail, and contain one intron located in the middle of the third cytoplasmatic loop. After some initial controversies, the available findings are now apparently more congruent. Nevertheless, discrepancies still exist, such as those in binding affinity, effects of 5-HT6 ligands on brain catecholamines and behavioral syndromes mediated by them. Much interest in 5-HT6 receptors was triggered by the evidence that some antipsychotics could bind to them. Subsequently, despite the lack of complete information on metabolic patterns of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic and anti-obese drugs. In any case, the available information on both the pharmacology of 5-HT6 receptors is still quite scant. Therefore, with the present paper we aimed at reporting a comprehensive review on the status of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.

Vulnerability to stress, anxiety, and development of dementia in old age.

OBJECTIVE: To identify the components of the neuroticism trait most responsible for its association with cognitive decline and dementia in old age. DESIGN: Longitudinal clinical-pathologic cohort study. SETTING: Chicago metropolitan area. PARTICIPANTS: A total of 785 older persons without dementia completed standard self-report measures of six components of neuroticism and then had annual clinical evaluations for a mean of 3.4 years and brain autopsy in the event of death. MEASUREMENTS: Incidence of clinically diagnosed Alzheimer disease (AD), change in global and specific cognitive functions, and postmortem measures of plaques and tangles, cerebral infarction, and Lewy bodies. RESULTS: During follow-up, 94 individuals developed AD. Higher levels of anxiety and vulnerability to stress were associated with increased risk of AD and more rapid decline in global cognition, with no effects for the other four trait components. In analyses of specific cognitive systems, neuroticism subscales were related to decline in episodic memory, working memory, and perceptual speed, but not in semantic memory or visuospatial ability. No component of neuroticism was related to the neuropathologic lesions most commonly associated with late-life dementia. CONCLUSIONS: Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety and their correlation with decline in the ability to process and retain new information.

Voxel-based morphometry studies of personality: issue of statistical model specification--effect of nuisance covariates.

There are an increasing number of studies on the localization of personality using voxel-based morphometry. Due to the complex analytic challenge in volumetric studies, the specification and treatment of the nuisance covariate (such as age, gender, and global measures) is currently not consistent. Here, we present a study in which we conducted voxel-based morphometry with Five-Factor Model (FFM) of personality traits (extraversion, neuroticism, openness to experience, agreeableness, and conscientiousness) that aimed to test the influence of NC specification in the determination of the results. In this study, 62 healthy subjects underwent MRI investigation and completed a German version of the FFM personality questionnaire. Voxel-based morphometry was used to investigate the correlation between the FFM personality traits and subtle brain structure. Different NC combinations were used during the model specification. Significant clusters were found only under the condition of some of the NC combinations but not under the others. In addition, we use the structure equation modeling (automated specification search from AMOS) to narrow down the possible choices of NC combinations according to a set of goodness-of-fit indices to identify well-fitted statistic models. As a final step, theoretical implications of the results are discussed, before accepting the selected model.

Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder.

Cortical plasticity is thought to occur following continuous barrage of nociceptive afferent signals to the brain. Hence, chronic pain is presumed to induce anatomical and physiological changes in the brain over time. Inherent factors, some pre-dating the onset of chronic pain, may also contribute to brain abnormalities present in patients. In this study we used structural MRI to examine whether patients with chronic temporomandibular (TMD) pain have abnormalities in gray matter (GM) within brain areas implicated in pain, modulation and sensorimotor function. We found that patients with TMD have cortical thickening in the primary somatosensory cortex (S1), frontal polar and the ventrolateral prefrontal cortex (PFC). These findings provide a structural basis for previous findings of TMD pain and cognitive sluggishness in TMD. We then examined the contribution of TMD characteristics to GM abnormalities. We found that 1) GM in the sensory thalamus positively correlated to TMD duration, 2) cortical thickness in the primary motor (M1) and the anterior mid-cingulate cortices (aMCC) were negatively correlated to pain intensity, and 3) pain unpleasantness was negatively correlated to cortical thickness in the orbitofrontal cortex (OFC). These findings suggest that an individual's TMD pain history contributes to GM in the brain. Lastly, we examined the contribution of a potential pre-existing vulnerability due to neuroticism. In the TMD patients, we found that there was an abnormal positive correlation between neuroticism and OFC thickness, in contrast to the negative correlation found in the healthy controls. Therefore, neuroticism may contribute to TMD pathophysiology. In sum, our data suggest that GM in the brain of patients with chronic TMD pain can be shaped by both personality and pain characteristics.

Aspects of neuroticism and the amygdala: chronic tuning from motivational styles.

Recent research and theory has highlighted the dynamic nature of amygdala activation. Rather than simply being sensitive to a few limited stimulus categories, amygdala activation appears to be dependent on the goals of the perceiver. In this study, we extend this line of work by demonstrating that the means by which a person seeks to accomplish a goal also modulates the amygdala response. Specifically, we examine the modulatory effects of the aspects of neuroticism (volatility/withdrawal), a personality variable that has been linked to both generalized anxiety and differences in amygdala sensitivity. Whereas Neuroticism-Volatility is proposed to be associated with the fight-flight-freeze system (FFFS) and a sensitivity for any cues of negativity, Neuroticism-Withdrawal is proposed to be associated with the behavioral inhibition system (BIS) and a generalized tendency toward passive avoidance. During fMRI scanning, participants were presented with positive, negative, and neutral images and were required to approach (move perceptually closer) or avoid (move perceptually farther away) stimuli in different blocks of trials. Consistent with hypotheses proposing a dissociation between these two aspects of neuroticism, participants higher in Neuroticism-Volatility had increased amygdala activation to negative stimuli (regardless of whether they were approached or avoided), whereas participants higher in Neuroticism-Withdrawal had increased amygdala activation to all approached stimuli (regardless of stimulus valence). These data provide further support for the motivational salience hypothesis of amygdala function, and demonstrate that both the ends and means of goal pursuit are important for shaping a response.

[Pathomorphism of neurotic disorders among military servicemen].

There were analyzed changes in popularity, structure and clinical peculiarities of neurotic disorders among military servicemen for the period 1986-2006. There were used epidemiological, clinical-archival and clinical-psypathological methods. It was established, that that internosological pathomorphosis of neurosis came out in reduction of their rates in general structure of psychological pathology. Internosological pathomorphosis has found reflection in narrowing of syndromes spectrum and its drift from hypochondriac to anxiety and depressive pole. Dynamic pathomorphosis consisted of less favorable indices of course and outcomes of these disturbances in 1992-1999, and also in reduction of the period of the period from the beginning of illness to hospitalization to a specialized department.

Unna sleeve for neurotic excoriations.

Neurotic excoriations are self-induced skin lesions produced because of compulsive scratching or picking. We present the successful use of the venerable technique of an Unna boot used as an Unna sleeve for neurotic excoriations of the upper extremities.

Individual differences in personality predict how people look at faces.

BACKGROUND: Determining the ways in which personality traits interact with contextual determinants to shape social behavior remains an important area of empirical investigation. The specific personality trait of neuroticism has been related to characteristic negative emotionality and associated with heightened attention to negative, emotionally arousing environmental signals. However, the mechanisms by which this personality trait may shape social behavior remain largely unspecified. METHODOLOGY/PRINCIPAL FINDINGS: We employed eye tracking to investigate the relationship between characteristics of visual scanpaths in response to emotional facial expressions and individual differences in personality. We discovered that the amount of time spent looking at the eyes of fearful faces was positively related to neuroticism. CONCLUSIONS/SIGNIFICANCE: This finding is discussed in relation to previous behavioral research relating personality to selective attention for trait-congruent emotional information, neuroimaging studies relating differences in personality to amygdala reactivity to socially relevant stimuli, and genetic studies suggesting linkages between the serotonin transporter gene and neuroticism. We conclude that personality may be related to interpersonal interaction by shaping aspects of social cognition as basic as eye contact. In this way, eye gaze represents a possible behavioral link in a complex relationship between genes, brain function, and personality.

Neuroticism and psychopathy predict brain activation during moral and nonmoral emotion regulation.

Functional neuroimaging has identified brain regions associated with voluntary regulation of emotion, including the prefrontal cortex and amygdala. The neural mechanisms underlying individual differences in emotion regulation have not been extensively studied. We investigated the neural correlates of neuroticism and psychopathic personality traits in the context of an emotion regulation task. Results showed that amygdala activity elicited by unpleasant pictures was positively correlated with neuroticism and negatively correlated with a specific psychopathic trait related to emotional underreactivity. During active attempts to decrease emotional responses to unpleasant pictures, superior and ventrolateral prefrontal activity was positively correlated with psychopathy, but not with neuroticism. In contrast, dorsolateral prefrontal activity was positively correlated with neuroticism, but not with psychopathy. Psychopathy was also negatively correlated with medial prefrontal activity in response to pictures depicting moral violations, suggesting reduced emotional responses to moral stimuli in individuals with high levels of psychopathic traits. These results demonstrate dissociable influences of different personality traits on neural activity associated with responses to emotional stimuli and on the recruitment of regulation-related brain activity during the active down-regulation of responses to negative emotional stimuli. These results have implications for the etiology of trait-based psychopathology involving emotional dysregulation.