Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer's disease.

Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this system, and especially of the SLC6A4 gene, may be associated with psychiatric disorders. In this study we aimed to evaluate the pleiotropic nature of SLC6A4 alterations and their association with the overall risk of brain diseases rather than disorder-specific. SLC6A4 variants, namely 5HTTLPR, STin2, rs2066713, rs25531, rs4251417, rs6354 and rs7224199 were investigated in 4 independent cohorts of subjects with specific psychiatric disorders, including Alcohol dependence disorder (ALC), Alzheimer disease (ALZ), Schizophrenia (SCZ) and Bipolar disorder (BPD). Other variables (biochemical parameters and Psychiatric scales scores) were also tested for association. SLC6A4 polymorphisms are not associated with the risk of developing major psychiatric disorders (SCZ and BPD); however some signals were detected in ALC (HTTLPR pd = 9.25 × 10-03, pr = 7.24 × 10-03; rs2066713 pd = 6.35 × 10-08; rs25531 pd = 2.95 × 10-02; rs4251417 pd = 2.46 × 10-03), and ALZ (rs6354 pr = 1.22 × 10-02; rs7224199 pd = 1.00 × 10-08, pr = 2.65 × 10-02) cohorts. Some associations were also observed on exploratory analyses. Our findings did not reveal any major influence on SCZ and BPD development; On the other hand, some alteration of the SLC6A4 sequence were associated with an increased risk of ALC and ALZ disorders, suggesting common pathways. The results of this study should be carefully interpreted since it suffers of some inherent limitations (e.g. cohort size, slight ethnic heterogeneity). Further analyses may provide better detail on the molecular processes behind SLC6A4 alterations.

Correction to: Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer's disease.

The following authors have double affiliations: Stefania Boccia, Marco Di Nicola and they should read.

A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.

BACKGROUND: Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. METHODS: Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. RESULTS: Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. CONCLUSIONS: The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels.

Factors associated with a negative outcome of medication-overuse headache: a 3-year follow-up (the 'CARE' protocol).

AIM: To evaluate factors associated with a negative outcome in a 3-year follow-up of subjects diagnosed with medication-overuse headache (MOH) (revised-ICHD-II criteria). METHODS: All consecutive patients entering the center's inpatient detoxification program were analyzed in a prospective, non-randomized fashion. All participants were assessed by a neurologist using an ad hoc patient record form. Personality was assessed using the Minnesota Multiphasic Personality Inventory (MMPI)-2, Chi-square test, one-way analysis of variance (ANOVA), and odds ratios (OR) were calculated as appropriate. RESULTS: One-hundred and fifty patients completed the follow-up (79.3% females, age 46.40 ± 11.31 years): 13 never stopped their drug overuse (A), 38 stopped their overuse, but relapsed at least once (B), and 99 stopped and never relapsed (C). The Group A patients differed from those in B + C as they were more frequently single (OR 0.134; P = 0.007) and unemployed (OR 3.273; P = 0.04), took a higher number of drug doses ( P < 0.001), and less frequently drank coffee (OR 3.273; P = 0.044). Personality profile: subjects in A scored higher than those in C on the following scales: Hypochondriasis ( P = 0.007), Depression ( P = 0.003), Paranoia ( P = 0.025), Fears ( P = 0.003), Obsessiveness ( P = 0.026), Bizarre Mentation ( P = 0.046), Social Discomfort ( P = 0.004), Negative Treatment Indicators ( P = 0.040), Repression ( P = 0.007), Overcontrolled Hostility ( P = 0.040), Addiction Admission ( P = 0.021), Social Responsibility ( P = 0.039), and Marital Distress ( P = 0.028). CONCLUSION: Disease outcome in MOH patients is influenced negatively by overuse severity and by specific psychological and socio-economic variables. Other possible modifier factors were voluptuary habits.

Differences in the personality profile of medication-overuse headache sufferers and drug addict patients: a comparative study using MMPI-2.

BACKGROUND: Medication-overuse headache (MOH) refers to headache attributed to excessive use of acute medications. The role of personality needs studies to explain the shifting from drug use to drug abuse. The main aim of this study is to study personality, according to Minnesota Multiphasic Personality Inventory, comparing MOH, episodic headache, substance addicts (SA) vs healthy controls. METHODS: Eighty-two MOH patients (mean age 44.5; 20 M, 62 F) and 35 episodic headache (mean age 40.2; 8 M, 27 F), were compared to 37 SA (mean age 32.5; 29 M, 8 F) and 37 healthy controls (mean age: 32.49; 20 M, 17 F). International Classification of Headache Disorders 2nd Edition criteria were employed. Chi-square test, Kruskal-Wallis test, and post hoc comparisons were used for statistics. RESULTS: MOH patients scored higher on Hypochondriasis, Depression (only females), Hysteria (only females) (P < .000). MOH did not show higher scores than episodic headache or healthy controls in dependency scales, while SA did. CONCLUSION: The data obtained show that MOH and SA do not share common personality characteristics linked to dependence. Although further studies are needed to understand if such a difference is related to instrumental characteristics or to yet undiscovered psychobiological characteristics of MOH patients; however, we hypothesize that the detected difference may rely on the fact that drug dependence in the 2 groups is promoted by entirely different needs: pleasure seeking in the SA group, pain avoidance in the MOH group.

AUTISM Spectrum Disorders and Suicidality.

The paper describes the suicidal ideation and behavior in a series of 26 adult psychiatric patients affected by Autism Spectrum Disorders (ASDs), the clinical features and the psychiatric comorbidity of patients presenting suicidal behavior, and the history of suicide or suicide attempt in their relatives. Two (7,7%) patients committed suicide. One (3.8%) patient attempted suicide twice, and one (3.8%) patient self-harmed by cutting his face and one finger of his hand with a razor. Eight (30.8%) patients presented suicidal ideation. Two (7.7%) patients had one relative who had attempted suicide, and two (7.7%) patients had one or more relatives who had committed suicide. Most patients with suicidal behavior or ideation presented psychotic symptoms. Although it is not clear whether the high suicidal risk is related with ASDs per se or with psychotic symptoms, a high index of suspicion is warranted in evaluating suicidal risk in patients affected by ASDs, whatever is their age, psychiatric comorbidity, and setting of visit.

Genetic variants associated with psychotic symptoms across psychiatric disorders.

BACKGROUND: Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis. METHODS: 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects. RESULTS: five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster. DISCUSSION: CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.

Genetic basis of psychopathological dimensions shared between schizophrenia and bipolar disorder.

Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity. Genome-wide analyses were performed at gene and gene set level, while 148 genome-wide significant loci previously associated with SCZ and/or BP were investigated. Each sample was analyzed separately then a meta-analysis was performed. SH3GL2 and CLVS1 genes were associated with suicidal ideation in SCZ (p = 5.62e-08 and 0.01, respectively), the former also in the meta-analysis (p = .01). SHC4 gene was associated with depressive symptoms severity in BP (p = .003). A gene set involved in cellular differentiation (GO:0048661) was associated with substance disorder comorbidity in the meta-analysis (p = .03). Individual loci previously associated with SCZ or BP did not modulate the phenotypes of interest. This study provided confirmatory and new findings. SH3GL2 (endophilin A1) showed a role in suicidal ideation that may be due to its relevance to the glutamate system. SHC4 regulates BDNF-induced MAPK activation and was previously associated with depression. CLVS1 is involved in lysosome maturation and was for the first time associated with a psychiatric trait. GO:0048661 may mediate the risk of substance disorder through an effect on neurodevelopment/neuroplasticity.

Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is potentially involved in the pathogenesis of anxiety. We carried out meta-analyses to evaluate the relationship between the BDNF Val66Met (valine, methionine) polymorphism and anxiety disorders (AD) or anxiety-related personality traits (ARPT). METHODS: Medline, Embase and PsycINFO were searched up to December 2007. We investigated 3 outcomes related to BDNF Val66Met polymorphisms: (1) clinically diagnosed cases of AD; (2) ARPT in subjects without psychiatric diagnoses, assessed either by the Neuroticism scale of NEO-Personality Inventory forms (NEO-PI, NEO-PI-R, NEO-FFI), or by (3) the Harm Avoidance (HA) scale of Tridimensional Personality Questionnaire (TPQ) or its extended version Temperament and Character Inventory (TCI). RESULTS: Seven case-control studies were selected for AD, including 1,092 cases and 8,394 controls, while 5 cross-sectional studies for Neuroticism (n = 1,633) and 4 for HA (n = 607). Both Met/Met and Val/Met individuals, as compared to Val/Val, showed a statistically significant lower Neuroticism score [SMD = -0.24 (95% CI: -0.44, -0.04), and -0.11 (95% CI: -0.22, -0.01), respectively]. No significant association was found between BDNF Val66Met polymorphism and AD [OR = 1.13 (95% CI: 0.85-1.52) for Met/Met versus Val/Val] or HA [SMD = 0.11 (95% CI: -0.19, 0.42) for Met/Met vs. Val/Val]. CONCLUSIONS: The low number of studies on this topic and their limited sample size, along with the inner limits in the definition of anxiety phenotypes, suggest caution in the interpretation of these results. Larger additional studies possibly investigating the interaction with other genes and environmental exposures are required to confirm these results.

Shorter telomere length in schizophrenia: Evidence from a real-world population and meta-analysis of most recent literature.

Schizophrenia is a severe, chronic mental disorder. Schizophrenia is visualized as an accelerated cellular aging syndrome characterized by early onset of cardiovascular disease causing premature mortality. In human aging involves alterations in telomere length (TL). To investigate the presence of TL shortening in schizophrenia and psychiatric syndromes associated, this condition was studied in leukocytes (LTL) of a sample of patients suffering from schizophrenia and other psychotic disorders, and compared with a group of non-psychiatric controls. We explored the relationship between LTL and age, gender, and smoking habit with the aim to control whether these potential confounding factors may influence the rate of telomeres shortening. We also performed a new comprehensive meta-analysis including studies on LTL in schizophrenia patients compared to healthy subjects published in the last two years and the results of the present study. Our results suggest that a diagnosis of schizophrenia, more than gender, age, cigarette smoking or alcohol drinking, is the most important condition responsible of the LTL shortening. A strong LTL shortening was observed in patients affected by schizophrenia, Schizoaffective disorder, and Psychosis not otherwise specified when they were younger than 50 years, while in the group of older subjects no major differences were observed. Additional evidence supporting the causal link of schizophrenia with accelerated telomeres shortening came from the analysis of the updated meta-analysis. The availability of a personalized profile of mechanistic pathways, risk factors, and clinical features may pose the basis for a rehabilitative treatment addressing individual needs of the psychiatric patients.

The challenge of psychiatric comorbidity to the public services for drug dependence in Italy: A national survey.

UNLABELLED: We evaluated the availability of resources and specific expertise for treating comorbidity at the Italian public Services for Drug Dependence (SerTs). A stratified sample of 100 SerTs was constructed and a specific questionnaire mailed to the clinical managers. The interview aimed at: characteristics of the respondent; theoretical knowledge of comorbidity; influence of dual diagnosis on clinical practice; general, human, and organisational resources; quality evaluation. MAIN RESULTS: (a) 90% of managers are medical doctors but <50% have a specialisation in psychiatry or qualification in psychotherapy; (b) about half of the managers have a fair knowledge of comorbidity; (c) the managers' estimate of prevalence is 25% for Axis I and 25-50% for Axis II comorbidity, and they consider the bad course of illness as the main cause of increased costs; (d) the SerTs' resources appear incomplete: psychiatric consultation and collaboration with therapeutic communities are available in about 90%, but routine assessment of psychopathology and day hospital or day care programs are lacking in over 50%; (e) about half of the managers declare themselves fairly satisfied about the treatments offered, but 80% complain about inadequate cooperation of the mental health services and >95% claim about inadequate education of their staff. The results were also analysed by factors of stratification: regional distribution, urban/rural location, and number of clients in care. In conclusion, the problem of comorbidity should be faced more effectively, particularly by means of improved organisational resources and continuing education of staff members.

Coping strategies in a sample of anxiety patients: factorial analysis and associations with psychopathology.

BACKGROUND: The relationship between coping styles and mental disorders has received considerable attention and instruments have been developed to assess coping strategies. The measurement by means of category systems has been criticized and a functional hierarchy of action types linked to the adaptive processes is preferred. We aimed to determine which factors may exist within the Brief-COPE (Brief Coping Orientation to Problems Experienced--COPE--Inventory) in an Italian sample of patients with anxiety disorders; and if these factors correlate with the severity of psychopathology or with other characteristics. METHODS: A total sample of 148 patients was recruited. The Brief-COPE inventory, the Symptom Check List 90-Revised, the Penn State Worry Questionnaire, the Zung Anxiety Status Inventory and the Zung Self-Rating Anxiety Scale were administered. RESULTS: Factor analysis of the Brief-COPE yielded nine factors accounting for 65.48% of the variance. Patients scored higher on Searching Support, followed by Acceptance, Changing Perspective, and Problem Solving. Associations between measures of psychopathology and factors of coping strategies, mostly Searching support and Avoidance, were found. CONCLUSIONS: Data of the present study support a nine-factor structure of the Brief-COPE that includes five broad dimensions of coping. Psychopathology was mostly related to Searching support and Avoidance factors, showing that these strategies may reflect ineffective ways of coping; Problem solving and Changing perspective could be a valid approach to moderate anxiety/depression symptoms and psychopathology in general.

DNA damage in non-communicable diseases: A clinical and epidemiological perspective.

Non-communicable diseases (NCDs) are a leading cause of death and disability, representing 63% of the total death number worldwide. A characteristic phenotype of these diseases is the accelerated aging, which is the result of phenomena such as accumulated DNA damage, telomere capping loss and subcellular irreversible/nonrepaired oxidative damage. DNA damage, mostly oxidative, plays a key role in the development of most common NCDs. The present review will gather some of the most relevant knowledge concerning the presence of DNA damage in NCDs focusing on cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, and neurodegenerative disorders, and discussing a selection of papers from the most informative literature. The challenge of comorbidity and the potential offered by new systems approaches for introducing these biomarkers into the clinical decision process will be discussed. Systems Medicine platforms represent the most suitable approach to personalized medicine, enabling to identify new patterns in the pathogenesis, diagnosis and prognosis of chronic diseases.

Beyond acetylcholinesterase inhibitors for treating Alzheimer's disease: α7-nAChR agonists in human clinical trials.

The neuronal nicotinic alpha7-acetylcholine receptor (α7-nAChR) is a promising and attractive drug target for improving cognitive deficits in neuropsychiatric and neurological disorders such as Alzheimer's disease (AD). α7-nAChR belongs to the family of ligand gated ion channels. α7-nAChR is expressed in key brain regions (e.g. pre- and frontal cortex, hippocampus). It is involved in essential cognitive functions such as memory, thinking, comprehension, learning capacity, calculation, orientation, language, and judgment. α7-nAChR binds to amyloid peptide (Aß) inducing either receptor activation or inhibition in an Aß concentration-dependent mode. Aß oligomers induce τ phosphorylation via α7-nAChR activation. α7-nAChR agonists and/or α7-nAChR positive allosteric modulators may be useful in AD therapy. The current review enlightens: (i) α7-nAChR neurobiology, (ii) α7-nAChR role in cognition and (iii) in AD, and (iv) the clinical status of the most promising molecules for the treatment of cognitive dysfunction in AD.

Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia.

S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR) of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI). 20 studies were included totaling for 994 cases and 785 controls. Schizophrenia patients showed 76% higher S100B blood levels than controls with mMR = 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR = 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR = 1.75 95% CI: 1.41-2.16). Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered.

A systems medicine clinical platform for understanding and managing non- communicable diseases.

Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.

Oxidative stress-related biomarkers in autism: systematic review and meta-analyses.

Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial.

INTRODUCTION: The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. METHODS: One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. RESULTS: On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). DISCUSSION: All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the 'gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation.

The assessment of post-detoxification anhedonia: influence of clinical and psychosocial variables.

Anhedonia, or the inability to experience pleasure, may be regarded either as a temperamental trait or as a state symptom of negative schizophrenia or melancholic depression. In substance use disorders, anhedonia was linked to hypoactivity of the dopaminergic mesolimbic system during protracted withdrawal. The authors investigated the influence of recent clinical and social-environmental factors on the hedonic capability and related psychopathology in a sample of 70 patients manifesting substance dependence (alcohol, opiates, multiple drugs) without severe comorbidity. Three symptom scales covering anhedonia (Snaith-Hamilton Pleasure Scale, SHAPS; Scale for the Assessment of Negative Symptoms, SANS; Bech-Rafaelsen Melancholia Scale, BRMES) were administered together with the European adaptation of the Addiction Severity Index (EuropASI). The composite scores from the seven areas of the EuropASI were introduced as independent factors in a stepwise regression analysis having symptom scores of anhedonia as dependent variables. Overall, the EuropASI composites do not explain the variability of the scores of anhedonia. Only in few cases, the regression models show a weak predictive capacity for medical status, alcohol use, and drug use composite scores, with R-square values ranging from 10 to 22%. Even if the study's limitations are noted, anhedonia appears as a psychopathological entity independent from other clinical and psychosocial features of treated addicts.