Ankyrin Repeat and Kinase Domain Containing 1 Gene, and Addiction Vulnerability.

The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.

Psychiatric comorbidity and plasma levels of 2-acyl-glycerols in outpatient treatment alcohol users. Analysis of gender differences. / Comorbilidad psiquiátrica y valores plasmáticos de 2-acilgliceroles en consumidores de alcohol en tratamiento ambulatorio. Análisis de las diferencias de género.

Alcohol addiction is associated with high psychiatric comorbidity. Objective stratification of patients is necessary to optimize care and improve prognosis. The present study is designed to gain insights into this challenge by addressing the following objectives: a) to estimate the prevalence of psychiatric comorbidities in a sample of outpatients seeking treatment for alcohol use disorder, b) to describe the existence of gender differences and c) to validate 2-acyl-glycerols as biomarkers of alcohol use disorder and/or psychiatric comorbidity. One hundred and sixty-two patients were recruited and evaluated with the semi-structured interview PRISM. The presence of psychopathology was associated with a greater number of criteria for alcohol abuse and dependence according to DSM-IV-TR. We found gender differences in psychiatric comorbidity, e.g., mood disorder, as well as in comorbid substance use disorders. The prevalence of lifetime psychiatric comorbidity was 68.5%, with mood disorders the most frequent (37%), followed by attention deficit disorder (24.7%) and anxiety disorders (17.9%). Substance-induced disorders were more frequent in mood and psychotic disorders, whereas the primary disorders were more prevalent in patients with comorbid anxiety disorders. We found that 2-acyl-glycerols were significantly decreased in comorbid anxiety disorders in alcohol dependent patients in the last year, which makes them a potential biomarker for this psychopathological condition.

La adicción al alcohol se asocia con una elevada comorbilidad psiquiátrica que complica el tratamiento, siendo necesaria una fenotipación clínica objetiva de estos pacientes para optimizar la atención y mejorar el pronóstico. El presente estudio aborda este problema mediante los siguientes objetivos: a) estimar la prevalencia y tipos de comorbilidad psiquiátrica de una muestra de pacientes que buscan tratamiento por uso de alcohol, b) describir las diferencias de género en su presentación y c) analizar los valores plasmáticos de 2-acilgliceroles (incluyendo el endocannabinoide 2-araquidonilglicerol), estudiando su posible valor como biomarcador de alcoholismo y/o comorbilidad psiquiátrica. Para ello se reclutaron 162 pacientes evaluados con la entrevista semiestructurada PRISM, para evaluar la presencia de comorbilidad y su carácter primario o inducido. Los resultados obtenidos indican que la presencia de psicopatología se asoció a un mayor número de criterios de abuso y dependencia de alcohol Se encontraron diferencias de género tanto en la comorbilidad psiquiátrica, especialmente en trastornos del estado de ánimo. La prevalencia de comorbilidad psiquiátrica encontrada a lo largo de la vida fue del 68,5%, destacando los trastornos del estado ánimo (37%), y seguidos por el trastorno por déficit de atención (24,7%, monitorizado específicamente por la entrevista WURS) y los trastornos de ansiedad (17,9%). Entre los trastornos del estado de ánimo y psicóticos fueron más frecuentes los inducidos, mientras que en los trastornos de ansiedad los primarios fueron más prevalentes. Además, se encontraron concentraciones disminuidas significativamente de 2-acilgliceroles en pacientes con trastornos de ansiedad comórbidos diagnosticados en el último año.

Startle-response based tasks and laboratory measures of impulsivity in abstinent alcoholic patients.

AIMS: It is well known that impulsivity is a risk factor for the development of Addictive Disorders, and more specifically Alcohol Use Disorders (AUD). Recently, the Startle-Response Based Tasks (SRBT) and its different forms of plasticity have been found to be impaired in the alcoholic population. This is the first study to explore the correlation between impulsivity laboratory tasks and the SRBT test, in order to determine whether impulsivity and startle response (SR) could be related and in turn, explain their association with Alcohol Dependence (AD). SUBJECTS: 40 men, who met DSM-IV criteria for AD and had been abstinent for at least one month. Impulsivity was assessed using three laboratory tests: Continuous Performance Test (CPT), Stop-Signal Task (SST) and Differential Reinforcement for Low-Rate Responding (DRL6). Patients also underwent the SR test. They were compared to 40 matched controls. RESULTS: Impulsivity laboratory measures tasks (SST and commissions of the CPT) correlated positively with the magnitude of SR (P < 0.05) and with habituation (P < 0.05). Scores on DRL6 correlated negatively with the magnitude of SR (P < 0.05). This was not found in the control group. CONCLUSIONS: The fact that impulsivity laboratory measures and the SR are correlated in patients but not in controls, could imply the existence of a common link for these two measures in alcoholic patients. Our findings support the hypothesis of the existence of two different vulnerability pathways for the development of AUD: anxiety and disinhibitory behaviour.

Clinical and Demographic Characteristics of Binge Drinkers Associated with Lack of Efficacy of Brief Intervention and Medical Advice.

UNLABELLED: Brief Counseling Intervention (BCI) and Medical advice (MA) are psychotherapeutic approaches used for the treatment of binge drinkers in Primary Care. Although binge drinking is a common pattern of alcohol misuse in Europe and in the US, no studies have evaluated those subjects who do not respond to Brief Counseling Interventions or Medical Advice. OBJECTIVE: To determine the clinical and demographic characteristics of binge drinkers in whom BCI or MA are not effective in reducing harmful alcohol use. METHODS: This is a secondary analysis of data from a randomized alcohol brief intervention trial with a 12-month follow-up period. A total of 674 subjects (89%) participated right through to the end of the study. The primary outcome measure was change in harmful alcohol use from baseline to 12 months. RESULTS: The strongest baseline predictors of harmful alcohol use during follow-up were educational status, young adults, and high number of cigarettes smoked, present family history of alcoholism, treatment condition and number of drinks per episode of binge drinking. CONCLUSIONS: Binge drinkers are a heterogeneous group that responds to brief intervention or MA but in a subgroup of them these interventions fail to prevent harmful alcohol use. Other interventions should be implemented for these subjects.

La Intervención Breve (IB) y el Consejo Médico simple (CM) son intervenciones psicoterapéuticas usadas para el tratamiento del consumo de alcohol por atracones en Atención Primaria. A pesar de la frecuencia de este patrón de abuso en Europa y en los Estados Unidos, ningún estudio ha evaluado las características de los sujetos que no responden a esas dos técnicas. Objetivo. Determinar las características demográficas y clínicas de los bebedores por atracones en los que la IB y el CM no son efectivos para la reducción del consumo perjudicial de alcohol. Métodos. Se trata de un análisis secundario de los datos obtenidos en un ensayo aleatorizado de intervención breve en alcohol con un período de seguimiento de 12 meses. Un total de 674 sujetos (89%) participaron durante todo el estudio hasta el final. La variable principal fue el cambio en el uso perjudicial de alcohol tras 12 meses de seguimiento. Resultados. Para ambos grupos de tratamiento las variables que predecían la continuidad en el consumo perjudicial tras el seguimiento eran: bajo nivel educativo, ser jóvenes, el número de cigarrillos fumados, la historia familiar de alcoholismo y la gravedad del consumo de alcohol basalmente. Conclusiones. Las características clínicas y sociodemográficas de los sujetos con un patrón de consumo de alcohol por atracones atendidos en Atención primaria influyen en el pronóstico de las Intervenciones breves y del Consejo Médico.

Dried human amniotic membrane as an antiadherent layer for intraperitoneal placing of polypropylene mesh in rats.

BACKGROUND: Intraabdominal peritoneal onlay polypropylene (PP) mesh repair of incisional hernia has the potential risk of adhesions, bowel obstructions, and intestinal fistulae. Fresh or cryopreserved human amniotic membrane (HAM) has been tested as an antiadherent layer in animals, with excellent outcomes. However, it has disadvantages: it is difficult to handle, and it is expensive to store. Another processing method is available: drying in a laminar flow hood and gamma irradiation. Because this method impairs the membrane's cell viability, it may affect its antiadherent properties. However, such properties may also result from the collagen matrix and its basement membrane, which remain after drying. The aim of the present study was to asses dried irradiated HAM in adhesion prophylaxis in rats. METHODS: Twenty-four female rats were randomized into two groups. In the first group (control group), PP meshes were placed in the intraabdominal space, and in the second group (treatment group), PP meshes coated with HAM were used. Animals were killed on day 30 after surgery. Adhesions and parietal prosthetic incorporation were assessed macroscopically and expressed as the average percentage of the covered area. The portion of the abdominal wall was then resected for histological testing. RESULTS: The treatment group had a significantly higher percentage of adhesions and parietal incorporation compared with the control group (p = 0.003). Histological testing showed a higher inflammatory response in the treatment group, with an intense foreign body reaction. CONCLUSIONS: Dried irradiated HAM does not prevent adhesion formation in intraabdominal peritoneal onlay PP mesh repair in rats. Any use of this biomaterial in adhesion prophylaxis must be undertaken respecting graft cell viability as much as possible.

[Integration of self-guidance groups for relatives in a public program of alcoholism treatment]. / Integración de los grupos de autoayuda para familiares en un programa público de tratamiento del alcoholismo.

Interventions with relatives of alcohol-dependent patients have shown effectiveness in engaging unmotivated patients into treatment. The Federation of ex-alcoholics, in the Community of Madrid, has a network of self-help centers (Centers to Promote Psychosocial Alternatives against Addictions, CPAA) spread throughout the Madrid's region where alcohol-dependent patients and their families receive attention. The aim of this study was to demonstrate that the integration of these facilities could improve the psychological condition of the relatives and the outcome on the patients' treatment. 188 patients attending the treatment program at "Hospital 12 de Octubre" and their relatives were randomized into two groups: Group A (n=94) (Standard program for patients and relatives delivered at our facility) and Group B (n=94) (where patients were treated with the standard program in our facilities and relatives attended a family group intervention at the CPAA) After 12 weeks, the CPAA conditions were significantly more effective than our standard program in improving psychological distress of relatives and in engaging patients into treatment. Patients belonging to group B had fewer drinking days during the treatment period. Our results support that psychological interventions delivered at CPAA centers are useful in improving psychological conditions of alcoholic patients' relatives than when undertaking the public alcoholism program. This intervention also improves outcome of alcoholic patients. The integration of these centers within public alcoholism treatment programs could provide a new way to treat alcoholism, based on collaboration of public facilities and patient associations.

Impairments of prepulse inhibition of the startle response in abstinent alcoholic male patients.

AIMS: Prepulse inhibition (PPI) of the startle reflex, which refers to the ability of innocuous sensory events to reduce the startle reflex, has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but experience is lacking in addictions and alcoholism. The aim of this study was to examine the existence of impairments in the startle response and PPI in abstinent alcoholic men. METHODS: Testing for PPI was conducted on 60 abstinent alcoholic men aged 18-65 years (mean 46.37) who met DSM-IV criteria for alcohol dependence and had been abstinent for more than a month at the time of testing. The comparison group were compared with 37 sex- age- and education-matched controls without alcohol dependence. RESULTS: Magnitudes of the startle reflex were lower in patients than in controls. The differences were statistically significant (P < 0.05) in trials with prepulses presented 30 and 120 ms before the onset of the startle stimulus. There was also a statistically significant (P < 0.05) reduced percentage of PPI when the prepulse was presented 30 ms before the startle stimulus. CONCLUSIONS: These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders could indicate the existence of a common vulnerability marker and explain the high degree of comorbidity between alcoholism and other mental illnesses.

[Cesarean birth: justifying indication or justified concern?]. / Operación cesárea: Indicación justificante o preocupación justificada?

BACKGROUND: Caesarean section is the most common surgery performed in all hospitals of second level of care in the health sector and more frequently in private hospitals in Mexico. OBJECTIVE: To determine the behavior that caesarean section in different hospitals in the health sector in the city of Aguascalientes and analyze the indications during the same period. MATERIAL AND METHOD: A descriptive and cross in the top four secondary hospitals in the health sector of the state of Aguascalientes, which together account for 81% of obstetric care in the state, from 1 September to 31 October 2008. Were analyzed: indication of cesarean section and their classification, previous pregnancies, marital status, gestational age, weight and minute Apgar newborn and given birth control during the event. RESULTS: were recorded during the study period, 2.964 pregnancies after 29 weeks, of whom 1.195 were resolved by Caesarean section with an overall rate of 40.3%. We found 45 different indications, which undoubtedly reflect the great diversity of views on the institutional medical staff to schedule a cesarean section. CONCLUSIONS: Although each institution has different resources and a population with different characteristics, treatment protocols should be developed by staff of each hospital to have the test as a cornerstone of labor, also request a second opinion before a caesarean section, all try to reduce the frequency of cesarean section.

Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia.

Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of dopamine levels by the enzyme catechol-O-methyltransferase (COMT). Here, we investigate the role of DRD1 and its interaction with the COMT gene in schizophrenic patients. In two gender-limited independent patient and control samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1. The DRD1 SNP and haplotype associations, as well as interaction effects with the Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses identified the T-A-T-C-T variant related to a protective effect (P = 0.008) and the G-G-T-C-C variant that showed a tendency to be a risk factor for the disorder (P = 0.012). A logistic regression analysis revealed a significant pattern of interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and rs11749676 (P = 4.5 x 10(-5)) SNPs. DRD1-associated haplotypes were exclusively related to schizophrenia in the Val homozygous subgroup of patients (T-A-T-C-T: P = 0.003; G-G-T-C-C: P = 0.006). In females, none of the DRD1 SNPs were linked to the disorder. Our genetic data suggest that DRD1 and COMT are epistatically associated with protection against and the risk of developing schizophrenia in a gender-dependent fashion, and support the role of dopamine dysfunction at the PFC in the pathophysiology of this disorder.

Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients.

The functional Val158Met polymorphism (rs4680) located at the gene that codes for the catechol-O-methyltransferase (COMT) has been extensively investigated in schizophrenia although current data are still controversial. Since COMT activity is sexually dimorphic, we carried out two independent studies in homogeneous samples of male and female Spanish schizophrenic patients. In males, we found an association between the homozygous Val genotype and the disorder, which resembled a recessive model (P = 0.022; odds ratio [OR] = 1.67). This Val homozygotes overrepresentation is produced at the expense of the heterozygous individuals decrease, whilst the Met homozygotes showed no differences when compared controls and patients. As a consequence, the heterozygous genotype in this sample had a protective effect (P = 0.03; OR = 0.65) and a strong deviation from Hardy-Weinberg equilibrium in male cases was observed (P = 0.006). In addition, a 2-SNP haplotype analysis (rs4818-Val158Met) confirmed there is an overrepresentation of the different homozygous Val genotypes in the male schizophrenic sample. Regarding females, we did not find any statistically significant association between COMT SNP and schizophrenia. In the light of this we suggest that the Val158Met SNP is involved in risk and protective genotypes for the vulnerability to schizophrenia in Spanish male population.

The role of behavioral impulsivity in the development of alcohol dependence: a 4-year follow-up study.

BACKGROUND: Although many studies have established a close relation between impulsivity and alcohol use disorders, little is known about the role of behavioral impulsivity in the development of these disorders. OBJECTIVES: To determine the role of 2 laboratory paradigms of impulsivity in the development of alcohol use disorders. METHODS: Follow-up study carried out with 471 participants diagnosed as heavy drinkers (HD) and followed-up for 4 years. Initially, they were compared with a healthy control group. Assessment of behavioral impulsivity was carried out with the Continuous Performance Test (CPT), and the Stop-Signal Task (SST) assessed behavioral inhibitory control. Differential reinforcement for low-rate responding (DRLR) was used to evaluate the delay reward dimension. The Structured Clinical Interview (SCID-DSM-IV) was used to diagnose alcohol dependence. RESULTS: The HD performed worse than the control group in all the behavioral tests of impulsivity. Performance in DRLR was the only behavioral impulsivity test that classified the HD correctly compared to controls. Logistic regression analysis indicated that performance on SST was a significant predictor [odds = 1.52(CI = 1.08-2.31)] of developing alcohol dependence. CONCLUSIONS: Our results support the relation between behavioral impulsivity and alcohol use disorders. The paradigm related to delay of reward may be a factor associated with the use of alcohol and the incapacity to control inhibition as dependence develops.

[Dual diagnosis in psychiatric inpatients: prevalence and general characteristics]. / Patología dual en pacientes psiquiátricos hospitalizados: prevalencia y características generales.

Comorbidity between a substance use disorder (SUD) and another psychiatric disorder is known as dual diagnosis. It is of great relevance due to its important clinical consequences and costs of care. There are practically no published studies on dual diagnosis prevalence in patients admitted to psychiatric hospitalization units in general hospitals (PHUGH) in our country. The objectives were to estimate the prevalence of dual diagnosis in psychiatric inpatients admitted consecutively to a Psychiatric Hospitalization Unit (Hospital Universitario 12 de Octubre, Madrid, Spain) in one year, to compare clinical and sociodemographic variables between the dual diagnosis group (DD group) and the group with a psychiatric disorder but no SUD (PD group), and to study the types of substances used. This is a retrospective study, based on the review of the clinical charts of the 257 patients admitted to this PHUGH in one year. The results showed that, excluding nicotine dependence, 24.9% of our inpatients had a SUD as well as another psychiatric disorder. A statistically significant predominance of men was found in the DD group, as well as a younger age at the time of the study, at the beginning of their psychiatric attention and on their first psychiatric admission, and they had received diagnoses of schizophrenia or related psychoses more often than the PD group, who had mostly affective disorders. The substances most frequently used in the DD group were alcohol (78.1%), cannabis (62.5%), and cocaine (51.6%). Due to the high prevalence and repercussions of dual diagnosis, it would be advisable to have specialized therapeutic programs for its treatment.

From dopaminergic genes to psychiatric disorders.

Individual vulnerability to develop neurological and psychiatric disorders is associated with both genetic and environmental factors. Association studies in patients have explored the contribution of gene variants in the dopaminergic system in these disorders. This system is involved in motor control, endocrinological function, the reward system and cognition. The diverse physiological functions of dopamine are mediated by five different dopamine receptors, encoded by the genes DRD1, DRD2, DRD3, DRD4 and DRD5. These genes have various types of polymorphisms that can produce changes in the genetic product or expression levels. In recent years, the development of new technologies for genetic analysis, and a wider comprehension of the genetic sequences of these genes have increased our understanding of the implications of the dopaminergic system in both health and pathological states. It has also allowed the identification of genetic variants that may represent risk or protection factors for a variety of psychiatric disorders.

Association in alcoholic patients between psychopathic traits and the additive effect of allelic forms of the CNR1 and FAAH endocannabinoid genes, and the 3' region of the DRD2 gene.

Little is known about the genetic factors that underlie the comorbidity between alcohol use disorder and antisocial personality disorder. Previous studies have associated both, dopaminergic and endocannabinoid systems to severe alcoholism with non-adaptive disrupted behaviours. In this work we have examined some gene variants involved in such systems in a sample of alcoholic patients to test whether there is a relationship with antisocial traits. The genetic analysis involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located nearby the DRD2 gene, the 10-repeat allele of a variable number tandem repeats (VNTR) of the SLC6A3 gene, the C385A FAAH SNP and the 3'-UTR microsatellite of CNR1 gene. The clinical study was performed in 137 Spanish alcohol dependent males. Antisocial Personality Disorder (DSM-IV) diagnosis was made by applying the International Personality Disorder Examination, and psychopathic traits were evaluated by the Hare's Psychopathy Checklist revised (PCL-R). The genotype distribution indicates there is a relationship between the TaqIA SNP, CNR1 and FAAH genes and PCL-R's Factor 1 in alcoholic patients. This relationship seems to be additive and independent and might be responsible for 11.4% of the variance in this PCL-R subscale. Our results suggest the implication of the dopaminergic and endocannabinoid systems in those processes leading to the comorbidity of alcoholism and antisocial behaviour.

[COMT Val158Met polymorphism and schizophrenia in a series of Spanish patients]. / Polimorfismo Val158Met de COMT y esquizofrenia: estudio de asociación en una muestra de pacientes españoles.

BACKGROUND AND OBJECTIVE: Catecol-O-methyl transferase (COMT) enzyme plays a significant role in the regulation of the dopaminergic system in the prefrontal cortex. Several studies have assessed the association between modifications of the COMT activity and schizophrenia, but without consistent results. COMT gene contains a single nucleotide functional polymorphism which produces the change of a valine for a methionine at position 158. The effect of this aminoacid change is a modification of COMT enzymatic activity: valine-COMT displays a significantly higher capacity of postsynaptic dopamine degradation than methionine-COMT. The objective of this study is to carry out a genetic association study of the functional polymorphism Val158Met in a sample of Spanish schizophrenic patients and healthy controls. PATIENTS AND METHOD: This is a case-control study made up of 177 patients and 141 healthy controls. All patients -115 males and 62 females, with ages between 27 and 49 years; mean (standard deviation) of 38 (10.7) years- were being treated in the outpatient Psychiatric Clinic of the Hospital Universitario 12 de Octubre, and fulfilled the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria for schizophrenia (n = 162) or schizoaffective disorder (n = 15). Control subjects -92 males and 49 females, with ages between 26 and 47 years; mean of 36 (9.4) years- were free from medical and psychiatric disorders. Genotype identification was done by means of human genetic molecular techniques coupled to ADN polymerase chain reaction and single strand conformational polymorphism (SSCP) of the COMT Val158Met polymorphism. RESULTS: No statisticaly significant differences were found in the allele frequencies for this polymorphism between patient and control samples. Nevertheless, in genotype analysis and when a model of recessive inheritance (Val/Val vs Val/Met and Met/Met) was assumed, a possible tendency towards statistical significance was observed. Our results do not allow to confirm the possible COMT gene variants contribution to schizophrenia etiopathogenesis, but they offer some evidence which would point to its implication in some patients subgroups. CONCLUSIONS: With the results obtained in this study a possible contribution of the COMT gene in schizophrenia etiopathogenesis cannot be ruled out. The issue of the possible effect of the COMT Val158Met polymorphism in schizophrenia would remain to be open and calls for the need to replicate this kind of studies in greater samples that will allow stratificate analysis by patients subgroups.

Psychological symptomatology and impaired prepulse inhibition of the startle reflex are associated with cannabis-induced psychosis.

BACKGROUND: Cannabis-induced psychotic disorder (CIPD) is a psychiatric disorder induced by cannabis consumption. The psychological and psychophysiological features of this disorder are still unknown. We aimed to examine the psychological, personality and psychophysiological features of patients with CIPD. This study is an analytical extension of our previously published data, which previously found prepulse inhibition (PPI) deficits in the CIPD group used in this current paper. METHODS: We used a sample of 45 patients with CIPD. After 9 months of follow up, these patients were assessed with a Symptom Checklist-90-R (SCL-90-R) questionnaire of psychopathology, with the Eysenck Personality Questionnaire, and with a psychophysiological paradigm of inhibition of the startle reflex (PPI). These results were compared with a group of patients with schizophrenia and cannabis abuse (SCHZ) ( n = 54); patients with cannabis dependence (CD) ( n = 21); and healthy controls ( n = 50). RESULTS: CIPD patients obtained significant higher scores in the SCL-90-R subscale of neuroticism. These patients showed PPI percentages similar to SCHZ patients within early attentional levels (30 ms). The variables with greater correlation, and that appeared in the CIPD group were interpersonal sensitivity, depression and phobia. CONCLUSIONS: Neurotic symptomatology and difficulties in inhibition of the startle reflex might be risk factors for developing CIPD.

The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors.

The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in murine brain after dopaminergic treatments. We found that Ankk1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon Ankk1 mRNA (1.004 ± 0.580-fold; t: 0.015, df: 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant Ankk1 mRNA downregulation (0.606 ± 0.057-fold; t: 2.786, df: 10, P = 0.02 and 0.588 ± 0.130-fold; t: 2.394, df: 11, P = 0.036, respectively). With respect the Ankk1 proteins profile, no effects were found after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of Ankk1 by specific pathways.

Plasma Chemokines in Patients with Alcohol Use Disorders: Association of CCL11 (Eotaxin-1) with Psychiatric Comorbidity.

Recent studies have linked changes in peripheral chemokine concentrations to the presence of both addictive behaviors and psychiatric disorders. The present study further explore this link by analyzing the potential association of psychiatry comorbidity with alterations in the concentrations of circulating plasma chemokine in patients of both sexes diagnosed with alcohol use disorders (AUD). To this end, 85 abstinent subjects with AUD from an outpatient setting and 55 healthy subjects were evaluated for substance and mental disorders. Plasma samples were obtained to quantify chemokine concentrations [C-C motif (CC), C-X-C motif (CXC), and C-X3-C motif (CX3C) chemokines]. Abstinent AUD patients displayed a high prevalence of comorbid mental disorders (72%) and other substance use disorders (45%). Plasma concentrations of chemokines CXCL12/stromal cell-derived factor-1 (p < 0.001) and CX3CL1/fractalkine (p < 0.05) were lower in AUD patients compared to controls, whereas CCL11/eotaxin-1 concentrations were strongly decreased in female AUD patients (p < 0.001). In the alcohol group, CXCL8 concentrations were increased in patients with liver and pancreas diseases and there was a significant correlation to aspartate transaminase (r = +0.456, p < 0.001) and gamma-glutamyltransferase (r = +0.647, p < 0.001). Focusing on comorbid psychiatric disorders, we distinguish between patients with additional mental disorders (N = 61) and other substance use disorders (N = 38). Only CCL11 concentrations were found to be altered in AUD patients diagnosed with mental disorders (p < 0.01) with a strong main effect of sex. Thus, patients with mood disorders (N = 42) and/or anxiety (N = 16) had lower CCL11 concentrations than non-comorbid patients being more evident in women. The alcohol-induced alterations in circulating chemokines were also explored in preclinical models of alcohol use with male Wistar rats. Rats exposed to repeated ethanol (3 g/kg, gavage) had lower CXCL12 (p < 0.01) concentrations and higher CCL11 concentrations (p < 0.001) relative to vehicle-treated rats. Additionally, the increased CCL11 concentrations in rats exposed to ethanol were enhanced by the prior exposure to restraint stress (p < 0.01). Concordantly, acute ethanol exposure induced changes in CXCL12, CX3CL1, and CCL11 in the same direction to repeated exposure. These results clearly indicate a contribution of specific chemokines to the phenotype of AUD and a strong effect of sex, revealing a link of CCL11 to alcohol and anxiety/stress.

The ANKK1/DRD2 locus is a genomic substrate for affective priming and recognition of angry faces.

INTRODUCTION: Ankyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion-related cognitive phenomena are associated with Taq IA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene. METHODS: We performed a genetic association analysis in 94 self-reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, Taq IA and C957T SNPs were genotyped. RESULTS: We found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the Taq IA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5' UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive-emotional processing. CONCLUSIONS: These results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.

The addiction-related gene ANKK1 in Parkinsonian patients with impulse control disorder.

Impulse control disorders (ICDs) comprise a wide spectrum of abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian treatment. Some ICDs share several essential features with substance use disorders. In this work, we have studied the addiction-related gene ankyrin repeat and kinase domain containing I (ANKK1) in a sample of PD patients involved in a multicenter study on ICD. We carried out the TaqIA ANKK1 single-nucleotide polymorphism (SNP) genotyping in PD patients. Clinical assessment of ICD was performed using the Questionnaire for impulsive-compulsive disorders in PD. We found no association between TaqIA SNP and ICD in PD patients (p = 0.565). However, when PD patients were grouped according the diagnosis of any ICD with a potentially addictive reinforcement (ICDARs), A1- TaqIA genotype showed significant association (p = 0.036). No association was found for the presence of punding in PD patients (p = 0.289). A logistic regression analysis confirmed the independent effect of the A1- genotype upon ICDARs (OR 8.76, 95 % CI 1.3-57.8, Wald = 5.805, p = 0.024). The TaqIA genotype A1- is associated to ICDAR in our sample and it may differentiate two types of disorders which are part of the ICD definition in PD patients.