Effects of Contingent and Non-Contingent Signals During Delay Interval on Response Acquisition by Rats

Research on delay of reinforcement effects under temporally defined schedulesof reinforcement suggests delay effects are diluted under short cycle durations.This conclusion is tentative because attempts to replicate the seminalstudy conducted by Weil (1984) differed from the original study in a number ofways. The present study attempted a more direct replication of Weil`s studyand also to extended the original manipulation to encompass two different signaleddelay of reinforcement procedures. Thirty-six naive rats were exposedto a repetitive time cycle of 32-s. The cycle was divided into two portions, td and t delta. A response during td produced food at the end of the cycle; responsesemitted during t delta had no programmed consequences. For someexperimental groups td was signaled by a response-produced signal; in othergroups a non-contingent signal occurred during td ; in still other experimentalgroups td was unsignaled. The placement of td was varied to produce twodifferent response-reinforcer temporal relations; td duration was also variedto assess the generality of the results. Response rates were considerablylower when td was at the beginning of the cycle than when the opportunityto respond was at its end. Non-contingent signals produced low rates of responding;in contrast response produced signals were associated with highresponse rates. In general the results show that delay of reinforcement hasdetrimental effects on response acquisition even under short reinforcementcycles. Both non-contingent and contingent signals have facilitative effects onthe response acquisition process, but the former favors low rates of respondingand the later favors high response rates

Lifetime Bipolar Disorder comorbidity and related clinical characteristics in patients with primary Obsessive Compulsive Disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

IntroductionBipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.MethodsWe assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.ResultsAmong primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).ConclusionThese findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.Peer reviewe

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Pobreza, recursos psicológicos y movilidad social

El presente estudio se realizó con el fin de explorar qué variables psicológicas y sociales (redes de apoyo social, depresión, autoestima, motivación al logro, bienestar subjetivo, estrategias de afrontamiento del estrés y escolaridad) son capaces de predecir la movilidad social (ascendente o descendente) de pobres extremos y no pobres, pertenecientes a una ?muestra de la Ciudad de México. La movilidad social se consideró como un constructo compuesto por indicadores como salario, puesto laboral, escolaridad y posesión de bienes materiales. Se utilizó un muestreo estratificado no probabilístico en el que participaron 346 pobres extremos y 312 no pobres, que habían experimentado una movilidad social positiva o negativa. Se realizaron análisis discriminantes que sugirieron, entre otras cosas, que no estar deprimido, tener un locusde control interno, estar satisfecho con la propia situación económica y ser crítico con el entorno social del país, predicen la pertenencia al grupo de movilidad social positiva. Se sugiere seguir la investigación sobre los aspectos psicosociales de la pobreza para propiciar un mejoramiento de las condiciones de vida de los pobres y con ello mayores tasasde crecimiento económico en el país

Personalized medicine in Psychiatric and substance use disorders

Tema del mesEl presente trabajo pretende instruir al lector en los diferentes avances que se han llevado a cabo en la genética de las enfermedades psiquiátricas y los trastornos por abuso de sustancias. Se mencionan los datos más recientes y relevantes en diferentes esferas abarcando los hallazgos de la medicina genómica en psiquiatría y adicciones. Concretamente, se discuten las asociaciones genéticas más importantes en las demencias (Alzheimer, corea de Huntington), los trastornos afectivos (depresión, trastorno bipolar), la esquizofrenia, el trastorno obsesivo compulsivo, el síndrome de Tourette y la dependencia a sustancias (alcohol, nicotina y otras drogas). El texto abarca las investigaciones que se han llevado a cabo en psiquiatría genética tanto a nivel global como en la población latina. Adicionalmente, se explican conceptos como el endofenotipo y la epigenética, puntos característicos para la comprensión de los padecimientos psiquiátricos y poligénicos. El concepto actual de medicina personalizada señala que la atención médica debe ser predictiva, preventiva, personalizada y participativa, estos puntos se analizan con un enfoque hacia la salud mental. Finalmente, se mencionan las contribuciones de la ciencia en el campo de la farmacogenética en medicamentos que actúan a nivel del sistema nervioso central.The aim of this paper is to instruct the reader in the various developments that have taken place in the genetics of psychiatric illnesses, and substance use disorders. The most recent and relevant data are listed in different areas covering the findings of genomic medicine in psychiatry and addictions. Specifically, the most important findings of the genetic associations of the following disorders are mentioned: dementia (Alzheimer's, Huntington's chorea), affective disorders (depression, bipolar disorder), schizophrenia, obsessive-compulsive disorder, Tourette 's syndrome and substance use disorders (alcohol, nicotine, and other drugs). The text covers the research that has been conducted in psychiatric genetics both globally and in the Latino population. In addition, concepts such as epigenetics and endophenotypes are addressed, as they are characteristic points for understanding psychiatric disorders and complex genetic diseases. The current concept of personalized medicine points out that medical care should be predictive, preventive, personalized and participatory. These topics are analyzed with a focus on mental health. Finally, the contributions of science in the field of pharmacogenetics on drugs acting on the central nervous system are discussed

Cigarette smoking in patients with obsessive compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS)

Obsessive compulsive disorder (OCD) showed a lower prevalence of cigarette smoking compared to other psychiatric disorders in previous and recent reports. We assessed the prevalence and clinical correlates of the phenomenon in an international sample of 504 OCD patients recruited through the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) network. Cigarette smoking showed a cross-sectional prevalence of 24.4% in the sample, with significant differences across countries. Females were more represented among smoking patients (16% vs 7%; p <.001). Patients with comorbid Tourette's syndrome (p <.05) and tic disorder (p <.05) were also more represented among smoking subjects. Former smokers reported a higher number of suicide attempts (p <.05). We found a lower cross-sectional prevalence of smoking among OCD patients compared to findings from previous studies in patients with other psychiatric disorders but higher compared to previous and more recent OCD studies. Geographic differences were found and smoking was more common in females and comorbid Tourette's syndrome/tic disorde

Epigenome-Wide Analysis Reveals DNA Methylation Alteration in <i>ZFP57</i> and Its Target <i>RASGFR2</i> in a Mexican Population Cohort with Autism

Autism Spectrum Disorders (ASD) comprise a group of heterogeneous and complex neurodevelopmental disorders. Genetic and environmental factors contribute to ASD etiology. DNA methylation is particularly relevant for ASD due to its mediating role in the complex interaction between genotype and environment and has been implicated in ASD pathophysiology. The lack of diversity in DNA methylation studies in ASD individuals is remarkable. Since genetic and environmental factors are likely to vary across populations, the study of underrepresented populations is necessary to understand the molecular alterations involved in ASD and the risk factors underlying these changes. This study explored genome-wide differences in DNA methylation patterns in buccal epithelium cells between Mexican ASD patients (n = 27) and age-matched typically developing (TD: n = 15) children. DNA methylation profiles were evaluated with the Illumina 450k array. We evaluated the interaction between sex and ASD and found a differentially methylated region (DMR) over the 5′UTR region of ZFP57 and one of its targets, RASGRF2. These results match previous findings in brain tissue, which may indicate that ZFP57 could be used as a proxy for DNA methylation in different tissues. This is the first study performed in a Mexican, and subsequently, Latin American, population that evaluates DNA methylation in ASD patients