Genetic predisposition to alcohol dependence: The combined role of polygenic risk to general psychopathology and to high alcohol consumption.

BACKGROUND: High alcohol consumption and alcohol dependence are only partly genetically correlated and they differ considerably in their correlations with other traits. The existence of genetic correlation among alcohol dependence and psychiatric disorders may be attributed to the presence of a general psychopathology factor, the p factor. This study investigates the relationship of polygenic risk to general psychopathology and to high alcohol consumption on alcohol dependence. METHODS: Participants were 524 alcohol-dependent patients and 729 controls. Polygenic risk scores (PRS) were computed for alcohol consumption (drinks per week) and nine psychiatric disorders. Principal component analysis (PCA) applied to the psychiatric PRS was used to calculate the first principal component as a proxy of the polygenic p factor. RESULTS: Both the polygenic p factor and the drinks per week PRS were associated with alcohol dependence in our sample. Both variables are only weakly correlated, contributing additively to the risk for alcohol dependence. Sensitivity analyses showed that the polygenic p factor was also associated with alcohol dependence in the subset of patients without any psychiatric or substance use comorbidity. CONCLUSIONS: Polygenic risk for alcohol dependence can be split at least into two components, involved in general psychopathology and high alcohol consumption. The first component of PCA based on PRS for different psychiatric disorders allows estimation of the contribution of the polygenic p factor to alcohol dependence. The pleiotropic effects of genetic variants across psychiatric disorders are mainly manifested as alcohol dependence in some patients.

Relationships between substance abuse/dependence and psychiatric disorders based on polygenic scores.

Genetic susceptibility to substance use disorders (SUDs) is partially shared between substances. Heritability of any substance dependence, estimated as 54%, is partly explained by additive effects of common variants. Comorbidity between SUDs and other psychiatric disorders is frequent. The present study aims to analyze the additive role of common variants in this comorbidity using polygenic scores (PGSs) based on genome-wide association study discovery samples of schizophrenia (SCZ), bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, major depressive disorder and anxiety disorders, available from large consortia. PGSs were calculated for 534 patients meeting DSM-IV criteria for dependence of a substance and abuse/dependence of another substance between alcohol, tobacco, cannabis, cocaine, opiates, hypnotics, stimulants, hallucinogens and solvents; and 587 blood donors from the same population, Iberians from Galicia, as controls. Significance of the PGS and percentage of variance explained were calculated by logistic regression. Using discovery samples of similar size, significant associations with SUDs were detected for SCZ PGS. SCZ PGS explained more variance in SUDs than in most psychiatric disorders. Cross-disorder PGS based on five psychiatric disorders was significant after adjustment for the effect of SCZ PGS. SCZ PGS was significantly higher in women than in men abusing alcohol. Our findings indicate that SUDs share genetic susceptibility with SCZ to a greater extent than with other psychiatric disorders, including externalizing disorders such as attention-deficit/hyperactivity disorder. Women have lower probability to develop substance abuse/dependence than men at similar PGS probably because of a higher social pressure against excessive drug use in women.

Genome wide analysis of rare copy number variations in alcohol abuse or dependence.

Genetics plays an important role in alcohol abuse/dependence. Its heritability has been estimated as 45-65%. Rare copy number variations (CNVs) have been confirmed as relevant genetic factors in other neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, epilepsy, or Tourette syndrome. In the present study, we analyzed the role of rare CNVs affecting exons of coding genes in a sample from Northwest Spain genotyped using the Illumina Infinium PsychArray Beadchip. After rigorous genotyping quality control procedure, 712 patients with alcohol abuse or dependence and 804 controls were used for CNV detection. CNV calling was performed using PennCNV and cnvPartition, and analyses were restricted to CNVs of at least 100 kb and including at least 10 single nucleotide polymorphisms. Logistic regression was used to test for the effect of CNV as well as number of genes affected by CNVs on case/control status, after adjustment for demographic and experimental covariates. We have found an excess of deletions (p = 0.008) and genes affected by deletions (p = 0.017) in cases. This effect was restricted to the 14.8% of affected genes that are intolerant to loss-of-function mutations (gene count p = 0.009). The importance of this subset of genes is emerging in other psychiatric disorders of neurodevelopmental origin, suggesting that disturbance in neurodevelopment mediated by genetic alterations may be a risk factor for alcohol use disorder.

Psychiatric Comorbidity in Patients from the Addictive Disorders Assistance Units of Galicia: The COPSIAD Study.

UNLABELLED: The objective of this study is to assess the prevalence of psychiatric comorbidity in patients under treatment within the addictive disorders assistance units of Galicia (Spain). MATERIAL AND METHODS: A total of 64 healthcare professionals performed clinical diagnosis of mental disorders (on DSM IV-TR criteria) in 2300 patients treated throughout March 2010 in 21 addictive disorders assistance units. RESULTS: 56.3% of patients with substance abuse/dependency also showed some other mental disorder, 42.2% of patients suffering from at least an Axis I condition and 20.2% from some Axis II condition. Mood and anxiety disorders and borderline and antisocial personality disorders were the most frequent disorders in both axes. CONCLUSIONS: A high comorbidity was found between mental and substance use disorders (SUD) in patients seen at the addictive disorders assistance units of Galicia.

[Psychometric performance of the 6th version of the Addiction Severity Index in Spanish (ASI-6)]. / Rendimiento psicométrico de la sexta versión del Addiction Severity Index en español (ASI-6).

This work analysed the psychometric properties of the 6th version of the Addiction Severity Index (ASI-6) translated and adapted to the Spanish language. A multicentre, observational and prospective design was used. A total of 258 participants were included, 217 were patients (35 stable patients and 182 unstable patients), and 41 were controls. The results show satisfactory psychometric performance of the ASI-6. The degree of the internal consistency of the standardized objective scores ranged between .47 and .95. As for test-retest reliability, the values were acceptable, varying from .36 to 1. The study of the internal structure revealed a good fit to a unidimensional solution for all scales taken independently. Regarding convergent-discriminant validity, the correlations between the primary and secondary scales of the ASI-6 and the Clinic Global Impression score were low, with values from .01 to .26. Likewise, 8 of the 15 scales differentiated between controls and unstable patients. The psychometric properties of the ASI-6 Spanish version seem to be acceptable, though it is necessary to carry out new studies to test metric quality with independent samples of patients.

Rendimiento psicométrico de la sexta versión del Addiction Severity Indez en español (ASI-6) / Psychometric performance of the 6th version of the Addiction Severity Index in Spanish (ASI-6)

El presente estudio examinó las propiedades psicométricas del Addiction Severity Index-6 (ASI-6) en su versión traducida y adaptada al español. Se realizó un estudio multicéntrico, observacional y prospectivo donde participaron un total de 258 sujetos, siendo 217 pacientes (35 estables y 182 inestables) y 41 controles. Los resultados muestran que el ASI-6 presentó un buen comportamiento psicométrico. Los niveles de consistencia interna de las puntuaciones objetivas estandarizadas de las escalas del ASI-6 oscilaron entre 0,47 y 0,95. Por su parte, los valores de fiabilidad test-retest fueron aceptables, oscilando entre 0,36 y 1. El estudio de la estructura interna del ASI-6 informó que todas las escalas, considerándolas de forma independiente, se ajustaron a una solución esencialmente unidimensional. En cuanto a la obtención de evidencias de validez convergente-discriminante, las correlaciones entre las escalas primarias y secundarias del ASI-6 y las puntuaciones en la Impresión Clínica Global de Gravedad fueron bajas, oscilando entre 0,01 y 0,26. Asimismo, ocho de las quince escalas del ASI-6 lograron diferenciar entre controles y pacientes inestables. La versión española del ASI-6 presenta propiedades psicométricas que pueden ser consideradas aceptables, aunque sería necesario llevar a cabo nuevos estudios que continúen examinando su calidad métrica en muestras independientes de pacientes(AU)

This work analysed the psychometric properties of the 6th version of the Addiction Severity Index (ASI-6) translated and adapted to the Spanish language. A multicentre, observational and prospective design was used. A total of 258 participants were included, 217 were patients (35 stable patients and 182 unstable patients), and 41 were controls. The results show satisfactory psychometric performance of the ASI-6. The degree of the internal consistency of the standardized objective scores ranged between .47 and .95. As for test-retest reliability, the values were acceptable, varying from .36 to 1. The study of the internal structure revealed a good fit to a unidimensional solution for all scales taken independently. Regarding convergent-discriminant validity, the correlations between the primary and secondary scales of the ASI-6 and the Clinic Global Impression score were low, with values from .01 to .26. Likewise, 8 of the 15 scales differentiated between controls and unstable patients. The psychometric properties of the ASI-6 Spanish version seem to be acceptable, though it is necessary to carry out new studies to test metric quality with independent samples of patients(AU)