Association of cannabinoid receptor genes (CNR1 and CNR2) polymorphisms and panic disorder.

Background and objectives: Panic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks along with sudden onset of apprehension, fear or terror. The endocannabinoid system (ECS) has a role in stress recovery, regulating anxiety. The aim of this study was to analyze potential genetic alterations in key ECS targets in patients suffering from panic disorders.Design and methods: We analyzed single nucleotide polymorphisms (SNPs) of the cannabinoid receptors (CNR1; CNR2) and the endocannabinoid hydrolytic enzyme fatty acid amide hydrolase (FAAH) genes in 164 Spanish PD patients and 320 matched controls.Results: No significant differences were observed in the SNPs of the CNR2 and FAAH genes tested. However, when analyzing genotype-by-sex interaction at A592G (rs2501431) and C315T (rs2501432) in the CNR2 gene, the presence of the G-allele in males was associated with a protective haplotype. Genotyping analysis revealed that variants in CNR1 confer vulnerability to PD, with a significantly increased risk associated with the G-allele (rs12720071) and C-allele (rs806368). This finding was consistent when analyzing genotype-by-sex interaction, where females presented a greater PD risk.Conclusions: Polymorphisms at the CNR1 gene may be a risk factor for PD contributing to sex-specific dysfunction in females.

Role of serotonergic polymorphisms in the clinical severity of the panic disorder.

OBJECTIVES: To investigate the association between three serotonergic polymorphisms (A-1438G [rs6311] of the HTR2A gene, STin2 VNTR and 5-HTTLPR of the SLC6A4 gene) and the severity of panic and depression symptomatology among mental health outpatients with diagnosis of panic disorder (PD). METHODS: 92 unrelated PD outpatients (DSM-IV criteria) from a homogeneous Spanish Caucasian population (mean age±SD, 35.9±12.4 years; 28 [30.4%] males) were assessed using the Panic and Agoraphobia Scale (PAS), and the Hamilton Depression Rating Scale (HDRS), and genotyped using standard methods. RESULTS: Age of onset of PD varied by STin2 VNTR genotype (F=3.21; p=0.045). On average, onset of PD occurred earlier for those with the 10/10 than for those with the 12/12 genotype (25.1 νs 33.3; p=0.043). No relationship was found between A-1438G, 5-HTTLPR, and STin2 VNTR genotypes and PAS or HDRS total scores. Variation in scores on the HDRS Anxiety subscale by A-1438G genotype almost reached statistical significance (F=3.03; p=0.053). Post hoc pairwise comparisons showed higher anxiety levels among A/G than among A/A carriers (4.1 νs 2.9; p=0.043). Finally, variation in scores on the Preoccupied with Health subscale of the PAS by 5-HTTLPR genotype approached statistical significance (F=2.56; p=0.083). Post hoc pairwise comparisons showed higher scores among L/S than among L/L carriers (2.4 νs 1.4; p=0.078). CONCLUSIONS: Our data provide support of an involvement of the serotonin system, particularly, the HTR2A gene in the severity of PD.

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.

Interleukin-1 gene complex in schizophrenia: an association study.

The aim of this study is to investigate the association between three polymorphisms of the interleukin-1 (IL-1) gene complex and schizophrenia. We genotyped 228 outpatients with schizophrenia (DSM-IV criteria) and 419 unrelated healthy controls. The following polymorphisms were analyzed: IL-1alpha -889 C/T, IL-1beta +3953 C/T, and IL-1RA (86 bp)n. No significant differences in genotype or in allelic distribution of the Il-1alpha, IL-1beta, and IL-1RA polymorphisms were found. Estimated haplotype frequencies were similar in both groups. Our data do not suggest that genetically determined changes in the IL-1 gene complex confer increased susceptibility for schizophrenia.

Instrumentos de evaluación de la dependencia de heroína / Evaluation instruments in heroin dependence

En el momento actual no existen pruebas específicas para el diagnóstico de la dependencia de heroína, de modo que una correcta anamnesis y la exploración clínica adecuada constituyen el pilar básico del mismo. No obstante existen una serie de instrumentos que abordan aspectos relevantes de esta patología, tales como la gravedad de la dependencia y la gravedad del síndrome de abstinencia, que pueden resultar de gran ayuda, al clínico, a la hora de establecer estrategias terapéuticas. La elevada prevalencia de comorbilidad psiquiátrica (sobre todo trastornos de la personalidad) detectada en estos pacientes hace necesario un abordaje comprehensivo de los mismos, siendo recomendable una evaluación detallada para descartar éstas u otras patologías psiquiátricas. Recordar, por último, que la dependencia de heroína se acompaña de gran discapacidad, siendo conveniente la valoración de su impacto. En líneas generales, se recomienda la utilización de instrumentos que cuenten con propiedades psicométricas reconocidas y que hayan sido adaptados y validados en castellano (AU)

No specific tests currently exist for the diagnosis of heroin dependence. Thus, diagnosis has to be based on an anamnesis and complete clinical examination. However, several questionnaires which embrace relevant aspects of this pathology exist. Assessment of the severity of addiction and the withdrawal syndrome can be a great help for the clinician at the time of establishing therapeutic approaches. The high prevalence of psychiatric comorbidity (personality disorders above all) detected in these patients makes necessary a comprehensive approach, and a careful evaluation is recomended to rule out these or other psychiatric disorders. Finally, as heroin dependence brings considerable disability, the evaluation of the impact of it is highly necessary. The employment of instruments with well known psychometric properties, and which have been validated and adapted for use in Spain, is recommended (AU)

Tratamiento farmacológico. Psicofármacos / Pharmacological treatment. Psychopharmacs

La terapia sustitutiva de nicotina ha sido, durante varios años, el único tratamiento farmacológico de primera línea en la cesación del hábito tabáquico. En el momento actual, existe otra sustancia que ha demostrado eficacia: bupropión. El bupropión fue desarrollado e introducido inicialmente en Estados Unidos (pero no en España) como antidepresivo atípico y, posteriormente, se observó su capacidad para reducir la urgencia de fumar y el craving, existiendo ensayos clínicos que han demostrado que es un fármaco efectivo en el abandono del tabaquismo. Los fármacos de primera línea para la cesación del hábito tabáquico (terapias sustitutivas de nicotina y bupropión) son útiles en el tratamiento de muchos fumadores, pero se muestras inefectivos en otro porcentaje importante de ellos. Evidencias procedentes de estudios preclínicos y clínicos ponen de manifiesto que diversos neurotransmisores (dopamina, noradrenalina, serotonina, opioides endógenos, entre otros) están implicados en la dependencia de nicotina y podrían contribuir tanto al mantenimiento del consumo de tabaco como a las recaídas. En los últimos años se han ensayado en el tratamiento de la dependencia de nicotina, con mayor o menor éxito, numerosos fármacos ya existentes como la mecamilamina, clonidina, naltrexona, antidepresivos, buspirona y selegilina. De igual modo, se están desarrollando e investigando nuevas aproximaciones terapéuticas como el rimonabant (bloqueante selectivo de receptores cannabinoides tipo 1) o las técnicas de inmunización activa y pasiva (AU)

Nicotine replacement therapies has been the first line drugs treatment for smoking cessation for many years. Currently other drug of proved efficacy is also available: bupropion. Bupropion was developed and initially introduced in the United States (but not in Spain) as an atypical antidepressant but was subsequently noted to reduce the urges to smoke and craving, and shown in clinical trials to be effective in smoking cessation. However, although some cigarette smokers are able to quit, many are not, and first line medications to assist in smoking cessation (nicotine replacement therapies and bupropion) are ineffective in many remaining smokers. Evidence from preclinical and clinical studies indicates thar several neurotransmitter systems mediate the neurobiology of nicotine dependence and might contribute to the process of smoking maintenance and relapse, including dopamine, noradrenaline, serotonine, endogenous opioids, etc. Several existing medications (mecamylamine, clonidine, naltrexone, antidepressants, buspirone, selegiline) are being tested as treatments for nicotine dependence. Furthermore, novel investigational agents (rimonabant –a selective cannabinoid-1 receptor antagonist- and pasive and active immunization) are under development as effective treatment for nicotine dependence (AU)

Complicaciones psicopatológicas asociadas al consumo de drogas recreativas / Psychopathological complications associated to recreational drug consumption

Esta revisión pretende evaluar las evidencias empíricas existentes en relación a las secuelas psicológicas persistentes asociadas al uso recreativo de MDMA. Numerosos casos clínicos sugieren que el uso regular de MDMA puede asociarse con trastornos psiquiátricos crónicos (psicosis, crisis de pánico, despersonalización, depresión, flashbacks) que persisten tras el cese del consumo. Es difícil determinar si el consumo de MDMA es el responsable directo de estos cuadros o es una asociación casual. Estudios comparativos entre usuarios regulares de MDMA y controles sugieren que la MDMA puede generar alteración selectiva de la memoria episódica, memoria de trabajo, y de la atención. Evidencias preclínicas apoyan dichos hallazgos: depleción serotoninérgica en usuarios importantes de MDMA, relación dosis-respuesta entre consumo de MDMA y gravedad del deterioro cognitivo. Hay que ser cautos al establecer relaciones de causalidad entre consumo de MDMA y trastornos mentales, usando datos procedentes de estudios transversales, ya que el uso de MDMA se asocia a patrón de policonsumo y, además, el comienzo del trastorno mental podría en muchas ocasiones preceder al uso de la sustancia (AU)

The aim of this review is to evaluate recent empirical evidence concerning the persistent psychological sequelae of recreational MDMA use. Clinical case reports suggest that regular MDMA use can be associated with chronic psychiatric disorders (psychosis, panic attacks, despersonalisation, depression, flashbacks) which persist after the cessation of drug use. However, it is difficult to determine whether MDMA use is directly responsible or is incidental. Neuropsychological comparisons of regular MDMA users and controls suggest that MDMA may be associated with selective impairment of episodic memory, working memory, and attention. Preclinical evidence supports these data: depletion of serotonin in heavy MDMA users, dose-response relationships between the extent of exposure to MDMA and the severity of cognitive impairment. Care should be taken in cross sectional studies in interpreting mental disorders merely as a consequence of MDMA use, as MDMA use might be associated with the use of multiple substances, and the onset of mental disorder might precede rather than follow the use of MDMA (AU)