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Currently, genome editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), are predominantly used to model genetic diseases. This genome editing system can correct point or frameshift mutations in risk genes. Here, we analyze and discuss the advantages of genome editing, its current applications, and the feasibility of the CRISPR/Cas9 system in research on psychiatric disorders. These disorders produce cognitive and behavioral alterations and their etiology is associated with polygenetic and environmental factors. CRISPR/Cas9 may reveal the biological mechanisms of psychiatric disorders at a basic research level, translating a suitable clinical approach for use in the diagnosis and treatment of psychiatric disorders. Genetic diagnosis and treatment for these disorders have not yet been fully established in psychiatry due to the limited understanding of their heterogeneity and polygenicity. We discuss the challenges and ethical issues in using CRISPR/Cas9 as a tool for diagnosis or gene therapy.
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Abstract Introduction Impaired control over drinking has been frequently cited in diverse theoretical descriptions regarding harmful alcohol use and is considered a DSM criterion for alcohol use disorder. Differences in the frequency of endorsement of impaired control have been viewed as a reflection of the severity of the problem. Moreover, it has been posited that the ability to place a limit on alcohol consumption may be mediated through enhanced craving. Objective In this study, we addressed the relationship between impaired control, self-reported craving, and alcohol dependence severity among heavy drinkers. Method We conducted a latent class analysis of impaired control dimensions (perceived control, failed control, and attempted control) of 208 heavy drinkers. To determine whether the identified classes could represent different forms of severity of the disorder, the best-fit model was contrasted with scores on the Alcohol Dependence Scale. Furthermore, we assessed the relationship between impaired control criteria (using the Impaired Control Scale [ICS]) with alcohol craving. Results We identified a three-class solution based on impaired control severity. A graded increase of the craving scores and alcohol severity among the three classes was also identified. Only the ICS items comprising perceived control and partially those related to failed control, but not those evaluating attempted control, distinguished the gradient among the latent classes. Discussion and conclusion This study provides further support of the proposal of a unidimensional continuum of severity among heavy drinkers and strengthens the theoretical relationship between impaired control and alcohol craving.
Resumen Introducción El deterioro del control sobre el consumo del alcohol se ha mencionado con frecuencia en diversas descripciones teóricas relativas al uso nocivo y es un criterio clínico del DSM para el trastorno por uso de alcohol. Las diferencias en la frecuencia con que se admite el deterioro del control se han considerado como un reflejo de la gravedad del problema. Además, se ha postulado que la capacidad de poner un límite al consumo de alcohol puede estar mediada por el deseo de consumirlo (craving). Objetivo En este estudio se abordó la relación entre el deterioro del control, el autoreporte del craving y la gravedad de la dependencia del alcohol en un grupo de bebedores fuertes. Método Se realizó un análisis de clases latentes usando las dimensiones del deterioro del control (control percibido, control fallido e intento de control) de 208 bebedores fuertes. Para determinar si las clases identificadas podían representar diferentes formas de gravedad del trastorno se contrastó el modelo más adecuado con las puntuaciones de la Escala de Dependencia del Alcohol. Además, se evaluó la relación entre los criterios de deterioro del control (utilizando la Escala de Control Deficiente, ECD) y el craving. Resultados Identificamos una solución de tres clases basada en la gravedad del deterioro de control. En esa solución se identificó una relación con el aumento graduado de las puntuaciones de craving y la gravedad de la dependencia entre las clases. Sólo los elementos de la ECD que comprenden el control percibido y parcialmente los relacionados con el control fallido, pero no los que evalúan el intento de control, distinguieron el gradiente entre las clases latentes. Discusión y conclusión Este estudio proporciona más apoyo a la propuesta de un continuum unidimensional de gravedad entre los usuarios de alcohol y refuerza la relación teórica entre el fenómeno de deterioro del control y el craving.
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Abstract: A genetic epidemiology paradigm employed in the identification of genes associated with a disease depends on the comparison of the frequency of common genetic variants between groups of individuals who possess a relevant trait versus those who do not show the trait (i.e., cases vs. controls genetic association study). The adequate classification of groups of contrast is therefore of seminal importance for the identification of relevant genes. For psychiatric disorders, the careful clinical evaluation of particular symptoms is the basis for the classification of the "affected or disease group". However, in many psychiatric genetics studies the constitution of the "control" or "normal" group has been based only on the absence of an overt expression of symptoms, where no particular emphasis is given to the symptom evaluation to exclude the phenotype. The use of psychometric instruments can help to assess some behavioral traits of clinical relevance. In turn, these assessments could help in the diagnosis, prognosis and treatment of disorders. Moreover, quantitative assessments let determine if these traits belong to the normal range of variation in a population or could be a deviation of the trend. The Symptom Checklist 90 (SCL90) is a 90-item self-report inventory that assesses the level of distress recently experienced by the subject. It is comprised of nine dimensions: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism and a General Severity Index (GSI). Although the SCL 90 is a well-accepted and widely used instrument in research and clinical practice in many countries, we found a scarcity of relevant studies for Latin America and a lack of normative data for Mexican populations. The aim of the present report was to evaluate the reliability and construct validity of the SCL 90. Method Subjects A Spanish translation of the original SCL90 English version was administered to a group of 228 subjects, comprised by relatives of patients, members of a family parents association, medical and paramedical staff, and college students. The SCL90 was included within a battery of clinical and psychometric assessments of individuals participating at ongoing research protocols on the genetics of personality and creativity. An additional group of 30 ambulatory psychiatric patients from the Instituto Nacional de Psiquiatría Ramón de la Fuente (INPRF) was also analyzed. The instrument was applied by experienced qualified personal. Statistical analyses Statistical analyses were performed using SYSTAT 8.0. Reliability was evaluated by assessing the response consistency obtained from those items with similar questions. The Cronbach's alpha coefficient was used as the measure of the internal consistency for all nine subscales for this purpose. Construct validity was assessed using two complementary criteria: a) evaluating pre-conceptual hypotheses and b) analysing psychometric data. In the first case, and based on previous reports showing that the level of distress is a function of social-demographic, gender and clinical status, it was hypothesized that the mean scores should be higher in women, younger people and individuals affected with a psychiatric condition. ANOVA and F statistics were computed using the mean scores and standard deviations for the nine dimensions and GSI. In addition, the extent of correlation between individual items and its own subscale dimension should be higher than the other subscales, and the level of correlation between each item and the GSI should be positive. In this case, a Spearman rank correlation matrix was constructed for the SCL90 items and the nine subscales, as well as the GSI. Results Internal consistency All but two of the nine SCL90 dimensions showed good internal consistency values (Cronmbach's alphas >0.7-0.85); with only hostility and paranoid ideation subscales reaching an acceptable value (>0.6-<0.7). The overall Cronbach's alpha score obtained for the GSI was 0.96. Construct validity Fifty-six of the SCL90 items showed a Spearman rank correlation coefficient value (r > 0.5), 23 items showed a moderate value (r >0.25 and <0.5), and only one item showed a weak correlation with its own scale (r =0.2). Only in one case (item 80) the highest correlation value did not correspond with its particular dimension. Mean scores for all of the nine dimensions of the SCL90, as well as the GSI, were higher in women compared to men, and in subjects < 25 years old. The ANOVA showed statistically significant differences (p< 0.01) for somatization, depression, obsessive-compulsive, interpersonal sensitivity, anxiety, hostility dimensions as well as for the GSI. Likewise, an ANCOVA, using age as a covariable, showed an age effect for the last five dimensions (p < 0.005), and in lesser degree for paranoid ideation (p =0.014). Likewise, both men and women patients populations showed higher scores for each dimension compared to general population. Comparison between Mexican and Argentine populations Independent sample t test showed meaningful differences for three scales (obsessive compulsive, interpersonal sensitivity, anxiety, as well as for the GSI) in men and women. Somatization was statistically different only for women from Argentina. Percentiles calculated for each one of all dimensions and the GSI showed a general tendency to be higher for the Mexican population compared with data from Argentina. Discussion The SCL90 is a self-report inventory where the subject reflects his/her perception about the degree of distress that he/she is experiencing. It is used by clinicians and researchers to gather information about the mental health of subjects. In the mental health field, the SCL90 has been employed world-wide to monitor the quality of the medical-psychological interventions, as well as a screening tool to identify psychopathology symptoms. We examined certain psychometric properties of the Spanish version of the SCL90, as there is a lack of normative data for Mexico. The internal consistency reliability for the scale as a whole and for individuals subscales was in general terms adequate for the group of individuals examined. Validity was assured throughout the confirmation of expected differences of groups of comparison and by the good correlation agreement among specific items and their particular dimensions. Compared to the only Latin American study, the mean scores for Mexican population were higher than in Argentina and even higher compared with the USA normative sample. Among others putative factors, translation issues (e.g. use of double negative sentences) and /or cross-cultural differences (e.g. demographic characteristics, socioeconomic differences) should be taken into account to explain these differences; therefore caution should be applied when comparing data of different populations. Among the limitations of this study we must include the analysis of a non-population sample of modest size. Nonetheless, we can conclude that the SCL90 inventory shows good psychometric attributes that may be useful for research and/or clinical purposes. Percentiles rank data can be used as a starting reference for others researchers interested in evaluating in a fast and simple way the psychological distress status of a particular individual, underlying the necessity of developing on a short-term basis normative data for the Mexican population.