Gino Pozzi

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.

Anhedonia and Substance-Related Symptoms in Detoxified Substance-Dependent Subjects: A Correlation Study

Anhedonia is a condition in which the capacity of experiencing pleasure is totally or partially lost, frequently occurring in mood disorders, as a negative symptom in schizophrenia, and in substance use disorders. In order to test a set of instruments for anhedonia in a population of detoxified opiate, alcohol and multiple substance-dependent subjects, 70 individuals were recruited from three different clinical settings. The following scales were applied: Snaith-Hamilton Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the Assessment of Negative Symptoms (SANS), specific withdrawal scales, and visual analogue scales (VAS) for hedonic capability and substance craving. The scales measuring anhedonia either directly (SHAPS, VAS for hedonic capability) or in some key items (SANS, BRMS) were significantly correlated with each other. The period of time since detoxification was inversely correlated with anhedonia and withdrawal symptomatology. Craving was positively correlated with anhedonia. Out of the total sample, only 18.5% could be defined as psychometrically anhedonic. The same correlations were found in this subsample. The composite instrument employed for assessing anhedonia and hedonic capability was found to be sensitive enough to detect such a dimension in the population considered, with the single scales significantly interrelated. In conclusion, we found interrelations between hedonic capability, craving and protracted withdrawal, particularly in opiate-dependent subjects. The strongest association occurred between hedonic capability and craving.

Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150—450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

THE EFFECT OF NEWER SEROTONIN-NORADRENALIN ANTIDEPRESSANTS ON CYTOKINE PRODUCTION: A REVIEW OF THE CURRENT LITERATURE

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

Behavioural addictions in bipolar disorder patients: Role of impulsivity and personality dimensions

BACKGROUND Behavioural addictions (BAs) can be understood as disorders characterized by repetitive occurrence of impulsive and uncontrolled behaviours. Very few studies have investigated their association with mood disorders. The present study was undertaken to determine the prevalence of the main behavioural addictions in a sample of bipolar outpatients in euthymic phase or stabilised by medications and to investigate the role of impulsivity and temperamental and character dimensions. METHODS One-hundred-fifty-eight Bipolar Disorder (BD) (DSM-IV) outpatients were assessed with tests designed to screen the main behavioural addictions: pathological gambling (SOGS), compulsive shopping (CBS), sexual (SAST), Internet (IAD), work (WART) and physical exercise (EAI) addictions. TCI-R and BIS-11 were administered to investigate impulsivity and personality dimensions mainly associated with BAs. The clinical sample has been compared with 200 matched healthy control subjects. RESULTS In bipolar patients, 33% presented at least one BA respect to the 13% of controls. Significantly higher scores at the scales for pathological gambling (p<.001), compulsive buying (p<.05), sexual (p<.001) and work addictions (p<.05) have been found. Self-Directness (p=.007) and Cooperativeness (p=.014) scores were significantly lower while impulsivity level was significantly higher (p=.007) in bipolar patients with BA than those without BA. CONCLUSIONS To our knowledge, this is the first study investigating the prevalence of behavioural addictions in BD showing a significant association of these disorders. BAs are more frequent in bipolar patients than in healthy controls and are related to higher impulsivity levels and character immaturity.

Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics

&NA; Compulsivity in alcohol‐dependent patients is a frequent cause of early relapse in the post‐detoxification period. The present study is a 2‐month trial on detoxified alcoholics undergoing a double‐blind placebo‐controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine‐treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short‐term outcome, while other factors are negatively associated with abstinence.

Oxcarbazepine improves mood in patients with epilepsy.

This study prospectively examined whether continued add-on treatment with oxcarbazepine (OXC) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy. Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale (HDRS), the Cornell Dysthymia Rating Scale (CDRS), the Beck Depression Inventory (BDI), and the Hamilton Anxiety Rating Scale (HARS). Forty controls (patients with epilepsy treated with antiepileptic drugs other than OXC) and 40 OXC-treated patients were enrolled and completed the study. In our study, a significant improvement in affect, as measured by the CDRS, was demonstrated during the course of OXC treatment for 3 months. HDRS and BDI scores also declined in the OXC-treated group, but these decreases did not reach statistical significance. In addition, 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry (score > or =20) demonstrated affective improvement consistent with a treatment-related antidepressant effect (score <20). Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant, the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood.

Pregabalin in outpatient detoxification of subjects with mild-to-moderate alcohol withdrawal syndrome.

In this open, prospective study we aimed to investigate the efficacy, medical safety and practicability of pregabalin in outpatient detoxification of alcohol‐dependent patients with mild‐to‐moderate alcohol withdrawal syndrome (AWS). Craving reduction, improvement of psychiatric symptoms and quality of life were the secondary endpoints.

Depressive Symptoms and Metabolic Syndrome: Selective Association in Older Women

The metabolic syndrome (MetS) is being increasingly found in older populations. Depressive symptoms are prevalent in elderly populations, and they are associated with adverse outcomes, chiefly cardiovascular. The aim of this study was to evaluate the association of the 30-item geriatric depression scale (GDS) score with MetS, as defined according to the National Cholesterol Education Program’s Adult Treatment Panel III (ATP-III) criteria, in all 353 participants aged 75+ years living in Tuscania (Italy). Metabolic syndrome was associated with the GDS score in a multivariable linear regression analysis in women (β s= 2.14, 95% CI = 0.14 to 4.14; P = .036), but not in men (β = —.84, 95% CI = —3.17 to 1.49; P = .476), after adjusting. Analysis of the interaction term confirmed (P = .022) that such an association differed according to sex. Metabolic syndrome is independently associated with depressive symptoms in community-dwelling older women. Older women with depression should be prompted to undergo screening for MetS. Conversely, elderly women with MetS should be assessed for affective disorders.

Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects.

OBJECTIVE Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms. METHOD Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3g/day, 21 received ALC at a dosage of 1g/day, and 20 were given placebo. ALC was given intravenously for 10days, followed by 80days of oral treatment plus a follow-up period of 45days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith-Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech-Rafaelsen Melancholia Scale). RESULTS The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p<0.05) in both the ALC 3g and ALC 1g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1g respect to placebo (p=0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo. CONCLUSION Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia.