M.T. Bascarán

Quality of life and disability in patients with obsessive-compulsive disorder

UNLABELLED The aim of this study is to describe the situation of Spanish obsessive-compulsive disorder (OCD) patients and compare it to that of the general population and other patient groups. METHODS Thirty-six OCD patients on maintenance treatment were evaluated using the Y-BOCS, SF-36, and DAS-S. Their SF-36 scores were compared to Spanish norms and to those obtained from U.S. OCD patients, schizophrenic outpatients, depressed outpatients, heroin dependents, patients on hemodialysis, and kidney transplant recipients. RESULTS Sixty-one percent of the patients had severe or extremely severe symptoms. Their quality of life was worse when compared with the Spanish norms in all SF-36 areas, but especially with respect to mental health. In contrast to U.S. OCD patients, social functioning is more impaired in the Spanish OCD patients. OCD patients reported the same quality of life as schizophrenics in the areas of mental health, but better in the areas of physical health. Compared with heroin dependents and depressed patients, their quality of life was worse. On mental health scales, OCD patients scored worse than somatic patients. CONCLUSIONS OCD in the Spanish population was shown to be associated with worse quality of life than for any other patient group (including physical groups), except schizophrenics.

Association study between obsessive-compulsive disorder and serotonergic candidate genes.

BACKGROUND To date, research examining the relationship between serotonergic genes and obsessive-compulsive disorder (OCD) has yielded conflicting results. The purpose of this study is to investigate the association between four serotonergic polymorphisms (STin2 VNTR and 5-HTTLPR of the SLC6A4 gene, and A-1438G (rs6311) and T102C (rs6313) of the HTR2A gene) and OCD. METHODS 99 OCD patients, 456 non-OCD psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS All groups showed Hardy-Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms were in complete linkage disequilibrium. OCD patients showed an excess of STin2.12 carriers (12/12, 12/10, and 12/9 genotypes) compared with healthy controls (chi(2) (1)=7.21, corrected p=0.021; OR=3.38, 95% CI=1.32-8.62) and non-OCD psychiatric patients (chi(2) (1)=6.70, corrected p=0.030; OR=3.24, 95% CI=1.27-8.26). However, no differences were found between non-OCD patients and healthy controls (chi(2) (1)=0.05, corrected p>1; OR=1.04, 95% CI=0.72-1.51). No significant differences were found with respect to A-1438G and 5-HTTLPR polymorphisms. CONCLUSIONS Our data provide supporting evidence of an association between the STin2 VNTR polymorphism of the SLC6A4 gene and OCD.

Maintenance treatment with depot opioid antagonists in subcutaneous implants: an alternative in the treatment of opioid dependence.

A report is presented of treatment of 156 patients (male 98%) with opioid dependence (ICD‐10 criteria) using a maintenance programme with depot opioid antagonists (naltrexone) as subcutaneous implants, started after an outpatient rapid antagonization regimen. The retention index in the treatment was from 80% in the sixth month, and 65% after one year. The patients were followed‐up for 1 year after discharge. For 6 months after discharge 55.4% were still returning for follow‐up visits and 20.8% after 1 year, all of them remaining abstinent to opioids. It is concluded that the programme is safe for the patients and shows a better retention index than programmes using oral antagonists, with an improved compliance (negative urine analysis) compared to the latter.

Differential role of serotonergic polymorphisms in alcohol and heroin dependence

BACKGROUND Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence. METHODS 165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups. CONCLUSIONS Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.

Use of MDMA and other illicit drugs by young adult males in northern Spain: A five-year study

Aim: To measure the prevalence of 3,4-methylenedioxymethamphetamine (MDMA) and other drug use in young males entering compulsory military service in Asturias (northern Spain) and to define trends in MDMA use in this group during the period from 1995 to 1999. We also sought to determine whether MDMA users have distinct personality features or higher levels of sensation seeking. Methods: 3,634 conscripts [mean age (SD) = 20.19 years (2.52)] who entered military service during the period between 1995 and 1999 were evaluated using the World Health Organization (WHO) questionnaire for drug consumption, the Eysenck Personality Questionnaire-A (EPQ-A), and the Zuckerman Sensation Seeking Scale. Results and Conclusions: The prevalence of lifetime, previous year and previous month MDMA use among military recruits between 1995 and 1999 was 10.9, 7.8 and 4.5%, ranking fifth among illicit drugs ever used. Once individuals used MDMA for the first time, they were likely to use it again, with 71% of individuals who had ever used MDMA reporting that they had used it during the past year (ranking second only to hallucinogens), and 41% reporting having used it in the last month. Compared to recruits who had never used MDMA (but who may have used other illicit drugs), MDMA users had a more extensive drug abuse history. Recruits who had used MDMA during the year prior to study had significantly higher scores on the Neuroticism and Psychoticism Subscales of the EPQ-A, and reported higher levels of sensation seeking.

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: data from an association study.

OBJECTIVE To investigate the association between dopaminergic polymorphisms [DRD2 -141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia. METHODS Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD)=36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD)=40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS There was a significant difference in genotype distribution for the DRD2 -141C Ins/Del polymorphism [(chi(2) (2)=12.35, corrected p=0.012]. The -141C Del allele was more common in patients than in controls [0.19 vs. 0.13; chi(2) (1)=9.14, corrected p=0.018, OR (95% CI)=1.57 (1.17-2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald=9.56 (4), p=0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR=0.51 (95% CI=0.30-0.89), p=0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR=2.45 (95% CI=1.16-5.17), p=0.019] and Gly/Gly [OR=3.80 (95% CI=1.24-11.63), p=0.019]. CONCLUSIONS This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.

Impact of substance use on the physical health of patients with bipolar disorder

Garcia‐Portilla MP, Saiz PA, Benabarre A, Florez G, Bascaran MT, Díaz EM, Bousoño M, Bobes J. Impact of substance use on the physical health of patients with bipolar disorder.

Association between the A-1438g polymorphism of the serotonin 2a receptor gene and nonimpulsive suicide attempts

Objective To investigate the association between four serotonergic polymorphisms [A-1438G (rs6311) and T102C (rs6313) of the serotonin 2A receptor gene, and STin2 VNTR and 5-HTTLPR of the SLC6A4 gene] and suicidal behavior. Participants and methods One hundred and ninety-three suicide attempters (SA) and 420 unrelated healthy controls from Asturias (Northern Spain) were genotyped using standard methods. Results A-1438G and T102C polymorphisms were in complete linkage disequilibrium in our population. Genotype and allele distributions showed no differences between SA and control participants. In nonimpulsive suicide attempts, however, we found an excess of the -1438A allele as compared with impulsive suicide attempts and the control group [χ2(2)=11.92, corrected P=0.021]. No other differences were found with regard to the impulsivity of the attempt. An excess of short allele carriers were found in the group of SA with high clinical lethality as compared with the low-lethality group [χ2(1)=4.93, P=0.026, not significant after Bonferroni correction]. The haplotype analysis showed no association between suicide attempt and haplotype distribution [likelihood ratio test (5)=4.40, P=0.493]. Conclusion Our findings suggest that the -1438A allele may predispose for nonimpulsive suicidal behavior.

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

OBJECTIVE To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior. SUBJECTS AND METHODS 227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS There were no differences in genotype frequencies between the three groups. The -1438A/G [χ(2) (df)=9.80 (2), uncorrected p=0.007] and IL-1α -889C/T [χ(2) (df)=8.76 (2), uncorrected p=0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of -1438G/G or IL-1α -889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df)=6.84 (2), p=0.033] and between the polymorphisms APOE and IL-1RA (86bp)(n) [LRT (df)=12.21 (4), p=0.016] in relation to suicide attempt lethality. CONCLUSION These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.

Use of cocaine by secondary school students in northern Spain.

Aim: To describe the prevalence of cocaine and other drug use in secondary school students in Oviedo (Asturias, Northern Spain) and determine the personality features and levels of sensation seeking in cocaine users. Methods: 2,862 secondary school students (mean age ± SD = 15.87 ± 1.48 years; 50.6% males) were interviewed during the 1998–1999 academic year. For evaluation, the World Health Organization questionnaire for drug consumption, the Eysenck Personality Questionnaire (EPQ) for adults and the Zuckerman Sensation Seeking Scale were used. Results: The prevalence of lifetime, previous year and previous month cocaine use among secondary school students was 6.1, 4.9 and 2.7%, respectively. Cocaine ranked sixth among illicit drugs ever used by this population. Once individuals had used cocaine for the first time, they were likely to use it again (44.8% of those who had ever used cocaine reported that they had done so in the previous month). Compared to students who had never used cocaine (but who may have used other substances), cocaine users had a more extensive drug abuse history. Students who had used cocaine at some point during their lifetime scored significantly higher on the EPQ psychoticism subscale and reported higher levels of sensation seeking. Conclusions: There is a significant rate of cocaine consumption amongst secondary school students of both sexes. Cocaine users are polyconsumers of other substances, both legal and illicit. Those who consume cocaine have a different psychological profile, characterized by high sensation seeking and high levels of psychoticism.