Psychiatric comorbidity in alcohol use disorders: results from the German S3 guidelines.

Alcohol use disorders (AUD) have a high comorbidity with mental disorders. Vice versa, alcohol consumption plays an important role in affective disorders, anxiety disorders, ADHD, schizophrenic psychosis, and other mental disorders. In developing the current interdisciplinary, evidence-based treatment guideline on screening, diagnostics, and treatment of AUD, available research on comorbid mental diseases in AUD has been compiled to generate recommendations for treatment. The guideline was prepared under the responsibility of the German Association for Psychiatry, Psychotherapy, and Psychosomatics (DGPPN) and the German Association for Addiction Research and Therapy (DG-Sucht). To meet the methodological criteria for the highest quality guidelines ("S3-criteria") as defined by the Association of Scientific Medical Societies in Germany (AWMF), the following criteria were employed: (1) a systematic search, selection, and appraisal of the international literature; (2) a structured process to reach consensus; and (3) inclusion of all relevant representatives of future guideline users. After assessing and grading the available literature, the expert groups generated several recommendations for the screening, diagnosis, and treatment of comorbid mental disorders. These recommendations were subdivided into psycho-, pharmaco-, and combination therapies. These are the first guidelines ever to make specific treatment recommendations for comorbid mental diseases in AUD. The recommendations extend to different treatment approaches including diagnostics and settings to present available effective and state-of-the-art treatment approaches to clinicians. Hitherto, many clinical constellations have not been addressed in research. Therefore, recommendations for future research are specified.

[On the legalization debate of non-medical cannabis consumption : Position paper of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Zur Legalisierungsdebatte des nichtmedizinischen Cannabiskonsums : DGPPN-Positionspapier.

Calls are increasing for the legalization of cannabis. Some legal experts, various politicians, political parties and associations are demanding a change in drug policy. The legalization debate is lively and receiving wide coverage in the media. The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) comments on the most important questions from a medical scientific perspective: can cannabis consumption trigger mental illnesses, what consequences would legalization have for the healthcare system and where is more research needed?

[Mental comorbidities of alcohol-related disorders]. / Psychische Komorbiditäten bei alkoholbedingten Störungen.

BACKGROUND: Alcohol-related disorders have a high comorbidity with mental disorders and vice versa, alcohol consumption plays an important role in affective disorders and schizophrenic psychoses. In developing the current S3 guidelines evidence-based knowledge on the rate and significance of comorbid disorders in alcohol use disorders has been compiled to generate recommendations for treatment. METHODS: In preparation for the guidelines, previous international guidelines and a systematic literature search were taken into consideration. Recommendations for various and specific clinical situations were derived from these sources based on evidence grading. Evidence and recommendations were subdivided into psychotherapy, pharmacotherapy and combination therapy, each having differential efficacies in the treatment of psychiatric symptoms and alcohol consumption behavior. Furthermore, a separate treatment pathway was developed for a stepwise approach to affective disorders for both comorbidities. CONCLUSION: Appearing for the first time in guidelines are specific treatment recommendations for comorbid mental diseases in alcohol use disorders. These recommendations extend to different treatment approaches including diagnostics and settings, affording clinicians more pragmatic relevance.

Assessing and treating alcohol relapse risk in liver transplantation candidates.

In Europe between 30 and 50% of all liver transplantations (LTX) are done within the context of chronic end-stage alcoholic liver disease (ALD). However, post-operatively 20-25% of these patients lapse or relapse into heavy alcohol use. Thus, assessment of alcohol relapse risk before enlisting and therapeutic follow-up during and after LTX is of utmost importance. However, as yet there are enormous differences between European countries and between transplant centers, with regard to the assessment methods and criteria and the implementation of therapeutic follow-up. Only the so-called '6-month abstinence' rule is widely used. However, there are not much scientific data validating its use in predicting relapse. Thus, there is a clear need of a more homogeneous approach, which was the focus of a symposium of the European Federation of Addiction Societies during the 14th conference of the European Society for Biomedical Research on Alcoholism, 2013 (ESBRA), entitled 'Liver transplantation: A European perspective'. In a follow-up on this symposium, the authors aim to sum up the evidence of psychiatric assessment criteria and psychiatric treatment interventions relevant in the context of patient selection and patient follow-up within ALD transplantation procedures. Based upon these findings, we propose elements of a procedure that can serve as a first step toward a model of good practice regarding addiction-specialist input within the pre- and post-transplantation period.

Dimensionality and stages of severity of DSM-5 criteria in an international sample of alcohol-consuming individuals.

INTRODUCTION: The DSM-5 alcohol use disorder (AUD) criteria proposal contains 11 criteria that include most of the DSM-IV abuse and dependence criteria plus craving. The aims of the current study in a large and international alcohol-consuming sample were to confirm the dimensionality of the DSM-5 AUD criteria and to differentiate grades of severity of DSM-5 AUD in subjects who pass the proposed DSM-5 diagnostic threshold of two criteria. METHOD: We used the World Health Organization (WHO)/International Society on Biomedical Research on Alcoholism (ISBRA) Study on State and Trait Markers of Alcohol Use and Dependence dataset. Subjects included in the analyses were aged ≥ 18 years and were recruited in five countries: Australia, Brazil, Canada, Finland and Japan. Assessment of AUD and additional characteristics was conducted using an adapted version of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS). Dimensionality of the DSM-5 criteria was evaluated using factor analysis and item response theory (IRT) models. The IRT results led to the classification of AUD patients into three severity groups. External validators were used to differentiate statistically across subgroups. RESULTS: A total of 1424 currently drinking individuals were included in the analyses. Factor and IRT analyses confirmed the dimensional structure of DSM-5 AUD criteria. More than 99% of the subjects could be allocated to one of the suggested severity subgroups. The magnitude of the external validators differed significantly across the severity groups. CONCLUSIONS: The results confirm the dimensional structure of the proposed DSM-5 AUD criteria. The suggested stages of severity (mild, moderate and severe) may be useful to clinicians by grouping individuals not only in the mild but also in the moderate to severe spectrum of DSM-5 AUD.

Prevalence of suicide attempts in pathological gamblers in a nationwide Austrian treatment sample.

BACKGROUND: For pathological gambling (PG), a 12-month prevalence rate of up to 0.66% has been reported. Multiple financial, occupational and relationship problems and losses, humiliation of the person and the environment are possible side effects and may lead to hopelessness, suicidal ideation and suicidal behavior. Suicide attempt rates among pathological gamblers of between 4% and 40% and suicidal ideation of between 12% and 92% have been reported. AIM: This study aims at assessing the prevalence of suicide attempts in PG and at elucidating differences between the patients with and without suicide attempt history (SAH) in a large nationwide Austrian sample. METHODS: Between 2002 and 2011, the Austrian Society for the Research of Non-Substance Related Addiction collected 862 questionnaires of pathological gamblers undergoing outpatient and inpatient treatment for PG in Austria. RESULTS: (a) Of all pathological gamblers, 9.7% had an SAH. (b) The SAH group suffered significantly more from a comorbid disorder and was more often in previous inpatient treatments. (c) The SAH patients had a longer time of an abstinence period in their PG career. DISCUSSION: One in 10 pathological gamblers has an SAH, demonstrating the relevance of suicidality in this population. Significant differences for several parameters were found for PG with and without SAH. However, a regression analysis only explained 15% of the variance. This suggests that suicidality must be considered in pathological gamblers in general.

Efficacy and safety of Ginkgo biloba extract EGb 761 in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebo-controlled, double-blind, multi-center trial.

OBJECTIVE: The study was conducted to explore the effects of EGb 761 (Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany) on neuropsychiatric symptoms (NPS) and cognition in patients with mild cognitive impairment (MCI). METHODS: One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory (NPI) were enrolled in this double-blind, multi-center trial and randomized to receive 240 mg EGb 761 daily or placebo for a period of 24 weeks. Effects on NPS were assessed using the NPI, the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale. Further outcome measures were the Trail-Making Test (A/B) for cognition and global ratings of change. Statistical analyses followed the intention-to-treat principle. RESULTS: The NPI composite score decreased by 7.0 ± 4.5 (mean, standard deviation) points in the EGb 761-treated group and by 5.5 ± 5.2 in the placebo group (p = 0.001). Improvement by at least 4 points was found in 78.8% of patients treated with EGb 761 and in 55.7% of those receiving placebo (p = 0.002). Superiority of EGb 761 over placebo (p < 0.05) was also found for the State-Trait Anxiety Inventory score, the informants' global impression of change, and both Trail-Making Test scores. There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients' global impression of change. Adverse events (all non-serious) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo. CONCLUSIONS: EGb 761 improved NPS and cognitive performance in patients with MCI. The drug was safe and well tolerated.

Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci.

We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus,showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P=1.17 × 10(-31); AAs: Arg369Cys, P=6.33 × 10(-17)) and ADH1C in AAs (Thr151Thr, P=4.94 × 10(-10)), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P=2.63 × 10(-11)), PDLIM5 in EAs (P=2.01 × 10(-8)), and METAP in AAs (P=3.35 × 10(-8)). We also identified a novel GWS association (1.17 × 10(-10)) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits.

Association of functional DBH genetic variants with alcohol dependence risk and related depression and suicide attempt phenotypes: results from a large multicenter association study.

OBJECTIVE: Dopamine-beta-hydroxylase (DBH) metabolizes the conversion of dopamine to noradrenaline. DBH, located on chromosome 9q34.2 has variants with potential functional consequences which may be related to alterations of neurotransmitter function and several psychiatric phenotypes, including alcohol dependence (AD), depression (MD) and suicidal behavior (SA). The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to investigate the role of DBH SNPs and haplotypes in AD risk and associated phenotypes (AD with MD or SA). METHOD: 1606 inpatient subjects with DSM-IV AD from four addiction treatment centers and 1866 control subjects were included. Characteristics of AD, MD and SA were obtained using standardized structured interviews. After subjects were genotyped for 4 DBH polymorphisms, single SNP case-control and haplotype analyses were conducted. RESULTS: rs1611115 (near 5') C-allele and related haplotypes were significantly associated with alcohol dependence in females. This association with female alcohol dependence also accounts for the significant relationship between this variant and comorbid conditions and traits. CONCLUSIONS: This study presents evidence for a potentially functional DBH variant influencing the risk for alcohol dependence while other comorbid conditions are not independently influenced by this SNP. However, the study also supports the possible role of the dopamine system in the etiology of female alcohol dependence.

A 24-week, multicentre, open evaluation of the clinical effectiveness of the rivastigmine patch in patients with probable Alzheimer's disease.

BACKGROUND: Cholinesterase inhibitors form the mainstay of treatment for persons with mild-to-moderate Alzheimer's disease (AD). The rivastigmine patch may increase compliance and the proportion of patients maintaining an efficacious dose compared with oral cholinesterase inhibitors. OBJECTIVE: To investigate the proportion of patients who reached and maintained the target rivastigmine patch dose compared with the target rivastigmine capsule dose reported in clinical trials. METHODS: This was a multicentre, 24-week, open-label study in persons with probable AD and a Mini-Mental State Examination (MMSE) score of ≥ 10 and ≤ 26. The primary outcome was the proportion of patients (ITT population) treated with 9.5 mg/24 h rivastigmine patch for at least 8 weeks at week 24. Secondary outcomes included week 24 MMSE, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), Trail Making Test Part A (TMT-A) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores. RESULTS: Overall, 208 participants received treatment and 155 (74.5%) completed the study. Within the ITT population, 147/182 patients (80.8%; 95% CI 75.0-86.5%) were treated for at least 8 weeks with the 9.5 mg/24 h rivastigmine patch; 135/182 patients (74.2%; 95% CI 67.8-80.5%) were treated for at least 8 weeks and completed the study. The most common adverse events were nausea (10.1% of patients), erythema (8.7%), pruritus (8.2%) and vomiting (7.2%). At week 24, patients treated with the rivastigmine patch showed improvements on MMSE, ADCS-ADL, ADCS-CGIC and TMT-A scores. Caregivers reported acceptance, preference and satisfaction with the patch. CONCLUSION: Transdermal delivery may allow more patients to reach and maintain therapeutic doses of rivastigmine compared with oral rivastigmine.

Short-term prospective comparison of prepulse inhibition between schizophrenic patients and healthy controls.

INTRODUCTION: The prepulse inhibition (PPI) of acoustic startle reflex is impaired in schizophrenic individuals compared to normal controls, and has been suggested to be a biomarker for sensorimotor gating. In fact, some cross-sectional studies suggest a different type of effect on PPI changes depending on the kind of antipsychotic treatment but few prospective studies have been conducted to investigate the short-term course of PPI alterations during the first few weeks of treatment. This study aimed to investigate schizophrenic subjects and controls over 4 weeks to analyze the course of PPI changes between groups at baseline and during follow-up, to determine whether potential PPI alterations are influenced by type of antipsychotic medication and whether these alterations are accompanied by changes in psychopathology. METHODS: 39 schizophrenic patients and 39 controls were enrolled into this open prospective trial. Acoustic startle response (PPI) measurements and clinical (PANSS) performance were obtained shortly after admission and every 14 days for a 4-week follow-up period (T1 to T3). RESULTS: Patients were treated with first and/or second generation antipsychotics in an open-label design. At baseline (T1) significant deficits were detected between schizophrenic subjects and controls for several PPI conditions. Neither was a relationship between type of antipsychotic treatment and PPI measures detected at baseline and during follow-up, nor was any association with PANSS psychopathology found. DISCUSSION: The results of our study confirm previous research on PPI deficits in schizophrenic subjects. As with previous prospective PPI studies in schizophrenic subjects, initial PPI deficits were not observed during the follow-up period, independent of the kind of antipsychotic treatment and severity of psychopathology. These findings may indicate that PPI serves as a biological marker of schizophrenic psychosis and sensorimotor gating independent of type of antipsychotic administered or severity of psychotic symptoms.

[Response and remission in schizophrenic subjects]. / Response und Remission bei an Schizophrenie erkrankten Patienten.

BACKGROUND: This naturalistic study investigates in detail symptom reduction during acute inpatient treatment (response), long-term symptom improvement in the post-acute phase (remission) and the rate of re-hospitalisations. MATERIAL AND METHODS: A total of 183 patients were enrolled. Criteria for response were PANSS total score and syndrome reductions of 20, 30, 40 and 50%. Remission criteria employed were based on recommendations from Andreasen et al. RESULTS: The average length of stay was 45.6 days (SD 42.7). PANSS total score response rates were found to be 63.9% for the 20% level and were reduced in the following consecutive levels by approximately 15%. Only 10.3% of the patients remitted during a 1-year follow-up period. At least one re-hospitalisation was reported for 43.9% of the subjects. CONCLUSION: Compared to previous randomised and controlled trials, the rates of response and remission are significantly lower. In daily inpatient care, the chronic course of schizophrenia is far commoner than expected from previous reports.

Alcohol consumption and expectations of its effects in the border region of Pomerania: comparison of German and Polish adolescents.

The study focused on expectations of alcohol effects and patterns of consumption in German and Polish adolescents in the border region of Pomerania. In 2005/2006 a cross-sectional study was conducted in various schools. Adolescents with an average age of 14 from one German town (Greifswald) and two Polish towns (Szczecin and Kolobrzeg) were assessed using the ESPAD (European School Project on Alcohol and Other Drugs) questionnaire. Altogether 757 (444 Polish and 313 German) students in their 7th and 8th grades were assessed. Differences between alcohol consumption patterns and expectations between Germany and Poland, and relationships between alcohol consumption and anticipated alcohol effects were tested. There is a difference in patterns of consumption between the two countries. Among all adolescents, expectations of positive alcohol effects dominated, and the negative effects were estimated to be less likely. In a country-specific comparison, German students estimated the occurrence of positive as well as negative effects to be likely. Adolescents who consumed a lot of alcohol in both countries estimated the positive effects to be stronger. Adolescents are more focused on short-term experiences than the long-term consequences of alcohol consumption. The results show potential targets for prevention and intervention of future risky consumption and alcohol use disorders.

No association of alcohol dependence with HOMER 1 and 2 genetic variants.

Several lines of evidence indicate that alterations of the central cortico-accumbens glutamate pathway are involved in the development and maintenance of alcohol- and substance-use disorders. The HOMER protein family is encoded by 3 genes HOMER (1-3) which are components of the excitatory postsynaptic density complex and function to modulate synaptic activity by the regulation of glutamate signaling. HOMER 1 and 2 have been reported to contribute to chronic alcohol-induced long-term neurochemical changes in the endogenous reward system. Data from animal models suggest a potential role of the Homer protein family in the development of alcohol and substance use. The aim of this study is to assess potential associations between HOMER 1 and 2 genetic variants in a larger sample of alcohol-dependent individuals and unrelated controls. Five genetic variants of HOMER 1 and 3 of HOMER 2 were genotyped in a multi-site sample of 1,923 German healthy controls and 2,039 alcohol-dependent subjects. Neither single SNP nor haplotype analysis could detect significant associations with alcohol dependence (AD) and related phenotypes. While most of the HOMER 1 and 2 SNPs are in low-to-moderate linkage disequilibrium, three major haplotypes of HOMER 1 and 4 haplotypes of HOMER 2 are present in the majority of alcohol-dependent and control subjects. In conclusion, our results suggest that single SNPs, respectively, haplotypes of the HOMER 1 and 2 genes are unlikely to play a major role in the pathophysiology of AD.

Cannabis withdrawal severity and short-term course among cannabis-dependent adolescent and young adult inpatients.

OBJECTIVE: While previous studies questioned the existence of a cannabis withdrawal syndrome (CWS), recent research provided increasing evidence of a number of clinical symptoms after cessation of frequent cannabis consumption. The aim of this study is to prospectively assess the course of CWS in a sample of cannabis-dependent inpatients and to provide an estimate of the proportion of subjects experiencing CWS. METHODS: 118 subjects, aged 16-36 years, diagnosed with a cannabis dependence (DSM-IV, assessed by SCID I) were enrolled in the study. CWS was assessed prospectively over 10 days using a modified version of the Marijuana Withdrawal Checklist. Personality dimensions were assessed with the NEO-FFI. RESULTS: 73 subjects (61.3%) completed all assessments over the observation period. Most symptoms peaked on day 1. Model-based analyses revealed a high and low intensity CWS group. Less than half of the patients belonged to the high intensity craving, psychological, or physical withdrawal symptoms group. Symptom intensity decreased almost linearly over time. Indicators of cannabis consumption intensity as well as personality dimensions, but not recalled withdrawal were related to membership in the high intensity CWS group. DISCUSSION: A clinically relevant CWS may only be expected in a subgroup of cannabis-dependent patients. Most subjects with an elevated CWS experience physical and psychological symptoms. The small to negligible associations between recalled and prospectively assessed symptoms raise questions about the validity of the former approach.

Personality disorders in alcohol-dependent individuals: relationship with alcohol dependence severity.

The rate of axis II disorders in alcohol-dependent individuals is suggested to be high. The aim of this investigation is to assess the rate of DSM-IV axis II diagnoses in alcohol-dependent inpatients and their correlation with clinical characteristics of alcohol dependence (AD). 1,079 inpatients with DSM-IV AD from three inpatient addiction treatment centers ('qualified detoxification', open psychiatric university hospital wards) were included. Characteristics of AD were obtained using standardized structured interviews. Diagnoses of DSM-IV personality disorders (PDs) were generated with SCID-II-PQ and SCID-II interviews. Alcoholism severity was measured using the number of DSM-IV criteria endorsed and age at first drinking. Approximately 60% of the sample had at least one PD. However, rates of Axis II disorders differed significantly across centers. The most frequent PDs were obsessive-compulsive, borderline, narcissistic and paranoid PD. Diagnosis of any PD was related to a more severe clinical profile of AD. Regression analyses revealed that obsessive-compulsive PD was related to the number of DSM-IV criteria endorsed while antisocial PD was related to early age at first drinking. The majority of alcohol-dependent individuals had one or more comorbid axis II disorders. Univariate and multivariate analyses indicate that different PDs are related to age at first dinking and alcoholism severity.

[Depressive disorders in dementia and mild cognitive impairments: is comorbidity a cause or a risk factor?]. / Depressive Störungen bei Demenzen und milder kognitiver Beeinträchtigung: Komorbidität, Ursache oder Risikofaktor?

Both depression and dementia occur by themselves or together in elderly subjects aged 65 and above. The aim of this review is to discuss several hypotheses which try to explain the frequent co-occurrence exceeding chance alone, based on a systematic literature search. A series of studies revealed potential biological similarities between both disorders which, however, were not found in all investigations. Lifetime history of depression can be considered as a distant risk factor for dementias. Depression occurs most frequently within one year before and after the onset of dementia, in which the association between both disorders is probably strongest. In a subgroup of subjects with more "cognitive reserve", depression was found to be a consequence of patient's realisation of beginning cognitive deficits. Several studies indicate that depression in Alzheimer and other dementia forms can be considered as a separate disease entity, as the clinical syndrome differs from depression in earlier periods of life. Studies on the therapy of depression in dementia have aroused increasing interest in recent years. Herewith, certain guidelines in the treatment of older patients with antidepressants must be followed.

[Personality disorders in a clinical sample of Cannabis dependent young adults]. / Persönlichkeitsstörungen bei einer klinischen Stichprobe von cannabisabhängigen jungen Erwachsenen.

INTRODUCTION: Cannabis addiction with comorbid personality disorders (PDs) is associated with a heavier individual burden of disease. Most previous studies focussed on singular disorders like borderline or antisocial PD, there is little data available on the full range of PD. Even less is known about the prevalence of PD with cannabis addiction in inpatient settings. The aim of this study is to investigate the frequency of PD and their relevance in treatment of young adult Cannabis-dependent inpatients. METHODS: 99 adolescents and young adults diagnosed with Cannabis dependence according to DSM I, were investigated during their detoxification treatment in an addiction treatment ward. Personality disorders were assessed using the SCID II questionnaire. RESULTS: The intensity of personality disorder traits was high in this inpatient sample. The probands showed a higher burden of disease from PDs other than the antisocial and Borderline PDs previously reported. Almost 90% of the subjects received the diagnosis of an antisocial PD, more than half had a paranoid and more than a third suffers from a Borderline PD. More than 35% of the sample had more than three PDs. There were no consistent relationships between PDs and concurrent consumption of other drugs, severity of drug addiction or delinquency. CONCLUSION: There is evidence of PDs in almost all inpatient Cannabis-dependent adolescents and young adults. Diagnosis and treatment of these subjects has to provide not only addiction-specific approaches but also strategies to improve dysfunctional behaviour caused by personality disorder characteristics.

5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder.

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine(1A) receptor (5-HTR(1A)) gene C -1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program 'BRAINS'. Patients who have the 5-HTR(1A) gene G allele had significantly smaller amygdala volumes than C/C genotype carriers (P = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR(1A) genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression (P = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR(1A) gene C -1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.

Citalopram neuropharmacological challenge in alcohol-dependent patients and controls: pharmacogenetic, endocrine and psychobehavioral results.

AIM: Alcoholism has been associated with long-lasting alterations in LHPA (limbic-hypothalamus-pituitary-adrenal) axis function, related to a dysfunction of the serotonergic neurotransmission. Functional polymorphisms of the serotonin system were previously reported to have significant influence on serotonin-induced neuroendocrine response. The aim of the study is to investigate in a double-blind, placebo-controlled approach, whether citalopram (a selective serotonin reuptake inhibitor, SSRI) would affect LHPA axis function as measured with ACTH (adrenocorticotrophic hormone) levels representing endocrine responsivity in 11 alcohol-dependent individuals compared to 12 controls. Furthermore we wanted to know whether functional polymorphisms (5-HTTLPR and 5HT2C Ser23Cys), have any influence on this responsivity. PATIENTS AND METHODS: Alcohol-dependent inpatients aged 36.45+/-7.7 years who were detoxified, without comorbid psychiatric/medical disorders or concurrent psychotropic medications, and 12 age-matched healthy controls aged 32.50+/-6.4 years were enrolled. Subjects also reported their subjective experiences like anxiety, craving and intoxication using visual analogue scales (VAS), side-effects were assessed by the serotonin syndrome scale (SSS). Measurements were taken at 8 timepoints at 30 mins interval, from -2 (60 mins pre-application) to +6 (180 mins post-application). Patients had a mean duration of illness of 8.91+/-3.4 years, consumed a mean of 326.36+/-220.8 g alcohol/day whereas control subjects consumed a mean of 32.50+/-41.4 g alcohol/day. A 0.4 mg citalopram/kg body weight dose was administered intravenously to patients (31.96+/-4.45 mg), and to controls (34.22+/-7.65 mg). RESULTS: ACTH levels were higher for both groups in the verum compared to placebo administrations across timepoints. 5HT2C Ser23 alleles effected significantly higher ACTH responses under placebo administration but attenuated the responses under citalopram administration. Considering both groups together, no influence of 5-HTTLPR alleles was found on ACTH levels in either group under either regimen. While citalopram administration did not reduce craving in alcohol-dependent patients, it increased anxiety in patients and controls compared to placebo administration. CONCLUSION: Despite the small differences in endocrine and subjective responses between alcoholic patients and controls, the effect of SSRI on endocrine response with respect to 5HT2C functional alleles deserves further investigation in larger samples to clarify whether this genetic variant constitutes a potential risk factor for changes in neuroendocrine functioning and subsequent psychiatric disorders.