Search

Background Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). Objective To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. Methods Systematic review and meta-analysis of pharmacovigilance registries and observational studies. Results Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40–46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9–89.8), 12.6% (95% CI: 6.3–20.8), 6.7% (95% CI: 4.2–9.9), and 2.9% (95% CI: 1–5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12–28.2) from vaccination was 1.9% (95% CI: 1.3%–2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine ( p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%–8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%–58.8%) and 0.1% (95% CI: 0%–0.2%) of vaccinations, respectively. Conclusion COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Background and ObjectivesAcute arterial ischemic stroke (AIS) has been reported as a rare adverse event following coronavirus disease 2019 (COVID-19) vaccination with messenger RNA (mRNA) or viral vector vaccines. However, data are sparse regarding the risk of postvaccination AIS and its potential association with thrombotic-thrombocytopenia syndrome (TTS).MethodsA systematic review and meta-analysis of randomized controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts, and case-series was performed with the aim to calculate the following: (1) the pooled proportion of patients presenting with AIS following COVID-19 vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; and (3) the proportion of TTS among postvaccination AIS cases. Patient characteristics were assessed as secondary outcomes.ResultsTwo RCTs, 3 cohort studies, and 11 registry-based studies comprising 17,481 AIS cases among 782,989,363 COVID-19 vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19 vaccine type was 4.7 cases per 100,000 vaccinations (95% CI 2.2–8.1; I2 = 99.9%). The pooled proportion of AIS following mRNA vaccination (9.2 cases per 100,000 vaccinations; 95% CI 2.5–19.3; I2 = 99.9%) did not differ compared with adenovirus-based vaccination (2.9 cases per 100,000 vaccinations; 95% CI 0.3–7.8; I2 = 99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA-based or vector-based vaccination. The pooled proportion of TTS among postvaccination AIS cases was 3.1% (95% CI 0.7%–7.2%; I2 = 78.8%).DiscussionThe pooled proportion of AIS following COVID-19 vaccination is comparable with the prevalence of AIS in the general population and much lower than the AIS prevalence among severe acute respiratory syndrome coronavirus 2–infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.

Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy–related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case reports or small case series (

Objective To investigate pathway-specific connectivity disrupted in psychosis. Methods We carried out a case study of a middle-aged patient who presented with new-onset psychosis associated with a space-occupying lesion localized in the right superior colliculus/periaqueductal gray. The study sought to investigate potential connectivity deficits related to the lesion by the use of diffusion tensor imaging and resting-state functional magnetic resonance imaging. To this aim, we generated a functional connectivity map of the patient’s brain, centered on the lesion area, and compared this map with the corresponding map of 10 sex- and age-matched control individuals identified from the Max Planck Institute–Leipzig Mind–Brain–Body database. Results Our analysis revealed a discrete area in the right rostral tectum, in the immediate vicinity of the lesion, whose activity is inversely correlated with the activity of left amygdala, whereas left amygdala is functionally associated with select areas of the temporal, parietal, and occipital lobes. Based on a comparative analysis of the patient with 10 control individuals, the lesion has impacted on the connectivity of rostral tectum (superior colliculus/periaqueductal gray) with left amygdala as well as on the connectivity of left amygdala with subcortical and cortical areas. Conclusions The superior colliculus/periaqueductal gray might play important roles in the initiation and perpetuation of psychosis, at least partially through dysregulation of left amygdala activity.

Background Recent research indicates that endocanabinoids (eCB) and heart rate variability (HRV) are associated with stress-induced experiences. However, these underlying mechanisms have not been elucidated. Purpose The aim of the present study is to investigate if exposure to acute and chronic stress promotes measurable changes concurrently to the peripheral eCB ligands and the HRV. Methods 13 candidates under intense preparation for their enlistment in the Hellenic Navy SEALs (H.N.S.) participated in the study. All subjects underwent mental state examination, while HRV variables in time and frequency domains recordings were acquired. Furthermore, at baseline and 30 days after prolonged and intensive physical exercise hair were collected in order to measure eCB ligands, such as anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the N-acyl ethanolamine (NAE) molecules: palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). Results Comparing basal hair concentrations of eCB ligands before and after intensive physical exercise, we found that AEA, PEA and OEA were notably increased (p Conclusions These findings suggest that endocannabinoid-HRV interrelations might share a short-term, and long-term adaptability of the changes in self-regulation associated with stress. Further studies are required to determine the validity of peripheral eCB signaling and HRV as a biomarker for different aspects of stress response. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Region of Attica

Introduction: Glycemic variability (GV) has been associated with worse prognosis in critically ill patients. We sought to evaluate the potential association between GV indices and clinical outcomes in acute stroke patients. Methods: Consecutive diabetic and nondiabetic, acute ischemic or hemorrhagic stroke patients underwent regular, standard-of-care finger-prick measurements and continuous glucose monitoring (CGM) for up to 96 h. Thirteen GV indices were obtained from CGM data. Clinical outcomes during hospitalization and follow-up period (90 days) were recorded. Hypoglycemic episodes disclosed by CGM but missed by finger-prick measurements were also documented. Results: A total of 62 acute stroke patients [48 ischemic and 14 hemorrhagic, median NIHSS score: 9 (IQR: 3–16) points, mean age: 65 ± 10 years, women: 47%, nondiabetic: 79%] were enrolled. GV expressed by higher mean absolute glucose (MAG) values was associated with a lower likelihood of neurological improvement during hospitalization before and after adjusting for potential confounders (OR: 0.135, 95% CI: 0.024–0.751, p = 0.022). There was no association of GV indices with 3-month clinical outcomes. During CGM recording, 32 hypoglycemic episodes were detected in 17 nondiabetic patients. None of these episodes were identified by the periodic blood glucose measurements and therefore they were not treated. Conclusions: Greater GV of acute stroke patients may be related to lower odds of neurological improvement during hospitalization. No association was disclosed between GV indices and 3-month clinical outcomes.

In the past few years, significant progress has been made in characterizing the function of the gut–brain axis, i.e., the interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. Preclinical studies described the important role of the gut microbiota in gut brain interactions Furthermore, gut microbiome has been linked to various serious mental illnesses, such as schizophrenia, bipolar disorder, anxiety disorders, depression. This chapter will describe the possible mechanisms that enhance the connection between them and the gut microbiome.

Gottlieb Burckhardt was a 19th-century Swiss psychiatrist who introduced the psychosurgical method known as topectomy as a means to relieve the symptoms of aggression and agitation in individuals diagnosed with mental disease. Specifically, he performed topical excision of part of the cerebral cortex on 6 patients with chronic schizophrenia. Most of these patients became more approachable and easier to manage, but they also showed signs of aphasia or seizures, and 2 died soon after the surgery. Burckhardt’s presentation of the results of his surgical procedures to the Berlin Medical Congress in 1890 caused an enormous controversy within the European medical community and resulted in his ostracism from it. He continued practicing, however and dispensing advice in his role as a mental hospital director, though he soon gave up his surgical endeavours. His innovative theory of higher cerebral functions anticipated the lobotomy procedure that was developed nearly half a century later by the neurologist Egas Moniz (1874-1955).

Summary Objective The present study compared the efficacy of agomelatine and sertraline in the treatment of symptoms of depression/anxiety, diabetes self-care and metabolic control in a sample of depressed patients with non-optimally controlled type 2 diabetes mellitus (DM). Method This was an observational open label study of 40 depressed patients with DM who were randomly assigned to receive either agomelatine or sertraline, and were assessed over a 4-month period for depression, anxiety, self-care, fasting plasma glucose, haemoglobin A1c and body weight. Results Lower anxiety and depression scores as well as higher self-care scores were measured in the agomelatine group compared with the sertraline group after 4 months of treatment. Although the main effects of treatment on final body weight and fasting plasma glucose were not significant, significantly lower final haemoglobin A1c levels were measured in the agomelatine group compared with the sertraline group. Both antidepressants were well tolerated and none of the patients dropped-out of the study. Conclusion The main finding of the present small pilot study was that agomelatine may be a promising agent in the treatment of symptoms of depression and anxiety as well as in the improvement of health-related behaviours, in depressed patients with type 2 DM possibly offering some advantages over sertraline. However, the lack of a placebo control group limits the generalisability of the findings and warrants further studies.

Although photophobia is a well-known symptom in various disorders, it has rarely been studied explicitly and its definition in a clinical setting can be somewhat elusive. Here, we assessed photophobia with a common psychometric tool in different conditions, in which light intolerance is considered part of the syndrome.A prospective study was undertaken in patients with migraine (MH), cluster headache (CH), tension-type headache (TH), essential blepharospasm (BS) and major depression (MD). Photophobia was assessed by the photophobia questionnaire (range 0-8). Symptom severity was measured in each patient group with appropriate scales. Finally, depression was assessed explicitly in each condition.Hundred and six subjects met the inclusion criteria (MH: 27, CH: 21, TH: 20, BS: 18, MD: 20). Photophobia scores differed between patient groups, with migraineurs showing the highest (6.63) and TH patients the lowest (2.10) scores (ranking: MH, BS, CH, MD and TH). Symptom severity as well as depression had little, if any, influence on the degree of photophobia.Photophobia is a core symptom of migraine but also constitutes a feature of other neurological conditions. The relative independence from other, disease-specific features, suggests that photophobia is a rather autonomous symptom.

In antiquity, physicians related depression or melancholic humour to cancer's pathogenesis. Galen (130-201 AD), sustained that melancholy could give rise to a tumour and his theory was repeated by the Byzantine and Arab physicians. In the 19th century, malignancy and depression became synonymous and people attributed their cancer to sadness. In 1893, the London surgeon Hebert Snow (1847-1930), performed an epidemiological study in order to clarify that link. The results revealed a probable connection. His work was followed by several large scale prospective studies some of which identified depression as a risk factor for cancer where others found no association. However, a possible explanation could be given by our current knowledge in immunology: inflammation and nonspecific immune activation play a role in the pathophysiology of depression and cancer growth.

The present study aimed to investigate for the first time, the alteration of α-N-acetylgalactosaminidase (nagalase) concentration in alcohol-dependent individuals without liver disease, before, during and at the end of the detoxification therapy.Forty-eight alcohol-dependent individuals without liver disease who were admitted for alcohol detoxification, and eighty-four healthy controls participated in this study. Patients' blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4-5 weeks). Nagalase concentration in serum was assessed by enzyme-linked immunosorbent assay.Nagalase concentration was significantly elevated in the patient samples in all serum collections as compared to the normal controls, with a progressive fall from admission to discharge (p-value0.001). Values differed significantly among the three time points, with a net shift to decrease, but remained still high, above normal control level at the end of the therapy. No significant correlations were detected among the nagalase levels and the liver enzymes values. Moreover, no significant correlation was found between the alterations of nagalase concentrations and the amount of consumed alcohol.The high nagalase concentrations in alcohol abuse might be associated with macrophage impairment through decreasing the endogenous macrophage-activating factor (MAF) production by Gc-protein. The possible pathogenetic association between nagalase activity and alcohol overconsumption remains a matter of further investigation. Nagalase could also serve as a marker of alcohol overconsumption for the evaluation of alcohol-dependent individuals before, as well as during the detoxification therapy.

Objective The objective of this 12-week open-label study was to evaluate the efficacy, safety, and tolerability of pregabalin as an adjunctive treatment to antidepressants in older patients suffering from depression and comorbid generalized anxiety disorder (GAD). Methods The initial sample of this open-label study consisted of 94 older patients fulfilling criteria for depression with comorbid GAD who were treated with antidepressants. Twenty of them who had received antidepressant monotherapy for an adequate time and shown partial response to the antidepressant prescribed, in terms of either anxiety or depressive symptomatology, followed the next phase. During the 12-week study period, pregabalin was gradually added to the previously prescribed antidepressant, reaching 225 mg/day over 4 weeks. Depression and anxiety scores as well as side effects were monitored. Within groups, differences of depression and anxiety scores at baseline and during the following 12 weeks of treatment were estimated with repeated-measure analysis of variance. Results A statistical significant reduction in depression scores was observed after the 4th week of treatment (p

The authors sought to determine the relative efficacy and tolerability of duloxetine versus citalopram and sertraline in the treatment of poststroke depression (PSD), anxiety, and fatigue. A group of 60 patients with PSD were assigned to receive duloxetine, citalopram, or sertraline and were assessed over a 3-month period for depression, anxiety, and fatigue. Improvement of depression and anxiety, but not fatigue, was observed in all study groups. Duloxetine was well tolerated and significantly more effective than citalopram and sertraline for the treatment of anxiety symptoms in PSD patients. None of the antidepressants used was effective for reducing symptoms of fatigue.

Summary Background It is unclear whether alcohol detoxification has an effect on factors that are involved in growth, metabolic functions and cell proliferation. Alcohol abuse is associated with low IGF-I levels that tend to rise after alcohol withdrawal. There is a paucity of studies on the course of IGFBP-3 (the main binding protein for IGF-I) after alcohol detoxification. Material/Methods We prospectively assessed IGF-I and IGFBP-3 changes at the time of admission and after 4 to 6 weeks of detoxification in an inpatient alcohol detoxification facility in 118 alcohol-dependent subjects given a regular hospital diet. No participants dropped out of the study. Results Changes in IGF-I after alcohol detoxification showed a marked dimorphism in altered hepatic biochemistry upon admission, with a rise in those with normal liver enzymes upon admission (p=0.016, Kruskall-Wallis) and a drop in those with elevated liver enzymes upon admission (p=0.05); the latter was noted in subjects that had consumed alcohol close to the time of admission. Overall, however, IGF-I and IGFBP-3 were within normal limits for most subjects both upon admission and after alcohol detoxification; no significant differences were detected among the examined parameters in men vs. women, and there were no significant correlations of IGF-I, IGFBP-3 or the IGF-I/IGFBP-3 molar ratio with BMI or age. Conclusions Regardless of hepatic enzymes’ elevation, alcohol detoxification had overall slight effects on IGF-I and IGFBP-3.

We assessed a set of biological (HDL, LDL, SGOT, SGPT, GGT, HTc, Hb and T levels) and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in a sample of 64 alcohol dependent patients, at baseline and after a detoxification treatment. Moreover, we recruited 47 non-consanguineous relatives who did not suffer alcohol related disorders and underwent the same tests. In both groups we genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR; rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located in genes whose impact on alcohol related behaviors and disorders has been hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the epistasis of these genetic variations upon the biological and psychological dimensions in the cases and their relatives. Further on, we analyzed the effects of the combined genetic variations on the short - term detoxification treatment efficacy. Finally, being the only not yet investigated variation within this sample, we analyzed the impact of the rs6313 alone on baseline assessment and treatment efficacy. We detected the following results: the couple rs6313 + rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive-compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at admission (p = 0.01) (hypochondriac symptoms). These results did not survive Bonferroni correction (p < or = 0.004). This lack of association may depend on the incomplete gene coverage or on the small sample size which limited the power of the study. On the other hand, it may reflect a substantial absence of relevance of the genotype variants toward the alcohol related investigated dimensions. Nonetheless, the marginal significance we detected could witness an informative correlation worth investigating in larger samples.

Clinical outcome of alcoholism may be partly under genetic control. The serotonergic system is involved in alcohol intake, and it has been widely investigated in alcohol dependence. Recently, attention has been focused on the neuronal tryptophan hydroxylase 2 gene (TPH2). TPH2 variants have been consistently associated with anxiety-related traits; since anxiety is critical for alcohol dependence treatment, in the present paper we investigated 9 SNPs within the THP2 gene in anxiety symptoms during the detoxification procedure. The sample comprised 68 alcohol-dependent patients who where evaluated with the Hamilton Rating Scale for Anxiety, before and after the detoxification procedure. Other psychopathological indicators of outcome, such as depression and anxiety sub-features were also investigated. We did not observe a role for TPH2 variants in the efficacy of treatment in relieving anxiety and other psychopathological symptoms. However, a haplotype that included the promoter rs4570625 polymorphism (associated with anxiety-related traits in previous studies) showed an association with the severity of anxiety symptoms on admission. This preliminary finding, although obtained on a small sample, may provide further support for a role of the TPH2 gene in emotional behaviors. Furthermore, the present study suggests the possible functional significance of the promoter rs4570625 polymorphism. The present preliminary results are of interest in alcoholism, given that comorbidity with anxiety represents a critical problem in treatment settings and response to detoxification.

There is evidence that GABAergic anticonvulsants can be efficacious in the treatment of alcohol dependence and in the prevention of alcohol relapse because these agents act on the substrate that is involved in alcoholism. Tiagabine, a selective GABA transporter1 reuptake inhibitor, may be a promising candidate for the treatment of alcohol-dependent individuals. In this randomized, open pilot study, we aimed to investigate the efficacy and tolerability of tiagabine as adjunctive treatment of alcohol-dependent individuals (N = 60) during the immediate post-detoxification period and during a 6-month follow-up period following alcohol withdrawal. A control non-medicated group of alcohol-dependent individuals (N = 60) was used for comparisons in terms of anxiety and depressive symptoms, craving and drinking outcome. Although a steady improvement in terms of psychopathology, craving and global functioning was observed in both groups throughout the study, subjects on tiagabine improved significantly more compared to the control subjects (P < 0.001). Furthermore, the relapse rate in the tiagabine group was lower than in the control group (7 vs 14.3%). Tiagabine was well tolerated and only a minority of the participants reported some adverse effects in the beginning of tiagabine treatment. Results from this study suggest that tiagabine is a safe and effective medication for the management of alcohol dependence when given adjunctively to a standard psychotherapy treatment. Further studies are warranted before definite conclusions can be reached.

Background: According to the self-medication hypothesis, individuals with depression and anxiety disorders use alcohol to control their symptoms and subsequently become dependent. Conversely, alcohol dependence disorder (ADD) can cause or exacerbate psychiatric disorders. This study analyzed the characteristics of depression and social phobia secondary to ADD. (1) What is their functional impact? (2) Are they independent or associated conditions? (3) Do they completely remit in abstinent individuals? (4) Is the remission of one disorder associated with the remission of the other disorder? Methods: Sixty-four inpatients with ADD were evaluated with depression and anxiety disorder scales upon admission to hospital and after 5 weeks of detoxification. Results: Baseline comparisons differentiated patients with a Hamilton Rating Scale for Depression (HDRS) score >35 (n = 50; 78%) from those with an HDRS score ≤35 by higher levels of generalized anxiety and lower global functioning. Patients with generalized social phobia [Leibowitz Social Anxiety Scale (LSAS) score >60: n = 20; 31.2%] were not distinguishable from those with an LSAS score ≤60 by depressive and anxiety disorder symptoms. In postdetoxification assessment, patients who remitted from depression (HDRS score Conclusions: Depression and social phobia secondary to ADD are independent conditions that do not completely remit after cessation of drinking. Specific treatments are needed to reduce residual depressive and anxiety symptoms in abstinent alcoholics.

Although amisulpride is considered to be a prolactin-raising atypical antipsychotic drug, a limited number of studies have documented the extent of its prolactin-elevating properties. In the present study the effect of amisulpride on plasma levels of prolactin and the reversibility of this untoward side effect were investigated.17 patients with various diagnoses received amisulpride (50-800 mg/day) or a combination of amisulpride plus other medication as needed. Plasma prolactin was determined 26.7+/-9.4 days (range: 13-50 days) after initiation of treatment and in 3 cases after a much longer period, and 14-51 days following its withdrawal.All patients on amisulpride had hyperprolactinemia (mean+/-S.D. prolactin levels: 62.5+/-33.0 ng/ml) with females exhibiting considerably higher prolactin levels than males. Following amisulpride discontinuation prolactin levels were significantly (p000) reduced (mean+/-S.D. prolactin levels: 12.3+/-6.7 ng/ml). No significant correlation was detected between prolactin levels and either amisulpride dosage or duration of administration.Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation.

The profile of coping mechanisms in a sample of 164 subjects (60 alcohol-dependent individuals, 47 depressed patients, 57 controls) was investigated. Data were collected over the period January-December 2004, at the Eginition Psychiatric Hospital of the Athens University Medical School in Athens, capital of Greece. The Albert Einstein College of Medicine Coping Styles Questionnaire (AECOM-CSQ; Plutchik & Conte, 1989), and the Hamilton Depression and Anxiety Rating Scales (Hamilton, 1959, 1960) were used for the assessment. Post hoc analysis of variance for comparisons between groups and logistic regressions using coping styles as predictor variables for group classification were used for data analysis. The main findings were that alcohol-dependent individuals could be distinguished from either depressed or control subjects on the ground of their coping mechanisms with stress, and that men and women use different patterns of psychological adaptation. More specifically, group classification in terms of specific coping styles could be predicted with an overall accuracy of more than 84%; in men, classification related to the coping mechanism of substitution, and in women to blame, reversal, and substitution. These findings may have implications for individually tailored psychotherapeutic interventions in alcohol-dependent individuals.

Background The course of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) was investigated in alcohol-dependent individuals without liver disease in order to ascertain the use of these cytokines as markers for the follow-up testing and the outcome of the detoxification treatment. Methods Forty-eight alcohol-dependent individuals were admitted for alcohol detoxification. Blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4–5 weeks). Serum IL-7, IL-10 and G-CSF were measured with a commercially available sandwich enzyme immunoassay. Results IL-7 concentration was steadily high from admission up to two weeks later and then showed a fall, yet still remaining significantly higher than in the control group at the end of the detoxification treatment. IL-10 concentration was significantly low on admission, presenting a linear increase during therapy and remained insignificantly low at the end. G-CSF was significantly elevated on admission and presented a linear fall ending up in almost normal values at the end of the detoxification therapy. Conclusions The alterations in the concentration of IL-7, IL-10 and G-CSF and their trend to normalization during the detoxification therapy are indicative of the generalized immune system disorder, caused by alcohol abuse. Further studies will help in further elucidating the pathophysiology of the immune system function in alcohol abuse, while immunological parameters might serve as biological markers and diagnostic tools for the assessment of the course and the outcome of the detoxification therapy.

Alcohol intake is a major cause of liver cirrhosis as well as chronic liver disease, and commonly coexists with mood disorders such as depression and anxiety. The aim of the present study was to investigate the possible correlation between liver dysfunction related to alcohol intake with anxiety and depressive-like symptomatology prior to and after the detoxification period.One hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated on an inpatient basis according to a standard detoxification protocol and measurements of serum levels of hepatic enzymes (ASAT, ALAT, γGT), and measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were also obtained at baseline and at weekly intervals over a period of 4 weeks.Increased levels of hepatic enzymes were observed upon admission that were significantly reduced (P0.001) following completion of the detoxification treatment. In addition, the psychopathological profile was improved at the end of the detoxification period and a significant correlation was obtained between the levels of hepatic enzymes and the global functioning of alcohol-dependent individuals.This observation further supports a relationship between the depressogenic action of alcohol and the disordered liver function observed in alcohol-dependent individuals, with possible implications in the diagnosis and treatment of mood disorders associated to alcohol abuse.

The aim of the present study was to evaluate the occurrence of large and small fiber neuropathy among alcohol-dependent subjects and to correlate neuropathy with the pattern of alcohol abuse, age of the subjects, nutritional status, and biochemical parameters. The study sample comprised 98 consecutive alcohol-dependent subjects without signs of malnutrition treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis. Polyneuropathy (PN) was graded using the neuropathy symptoms score and neurologic disability score, conduction velocity studies, and quantitative sensory tests. Seventy-seven men and 21 women aged 27-70 years took part in the study. PN was diagnosed in 57 subjects (58.2%). PN of both large and small fibers was found in 25 patients (25.5%); exclusively small fiber neuropathy was observed in 12 (12.2%) and exclusively large fiber neuropathy in 20 patients (20.4%). Neuropathy was significantly correlated with the age of the subjects, duration of alcohol abuse, liver dysfunction, macrocytosis, and blood sugar levels upon admission. PN was significantly more frequent in males than in females. The two groups of exclusively large and exclusively small fiber neuropathy did not differ significantly in any clinical and laboratory parameter. Subclinical neuropathy (stage 1) was observed in 11.2%, which also did not differ significantly in any clinical and laboratory parameter from the stage 2 PN group subjects. Our findings indicate the direct toxic effect of alcohol on peripheral nerve fibers as the main etiologic factor of alcoholic PN. Long-standing hyperglycemia may be another contributing factor. Impaired vitamin B(12) utilization may be also involved.

Symptoms of anxiety and depression are common in a large proportion of alcohol-abusing/dependent individuals during alcohol detoxification. The aim of this study was to examine the impact of a combined psychotherapeutic-psychopharmacological (either with mirtazapine or venlafaxine) treatment of these symptoms during the early withdrawal phase of alcohol compared to a group treated only with psychotherapy. A total of 60 alcohol-dependent/abusing subjects randomly assigned to three groups (psychotherapy, psychotherapy plus mirtazapine, psychotherapy plus venlafaxine) were studied. Assessment of psychopathology and global functioning throughout a 4-5-week detoxification period was done by the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Global Assessment Scale (GAS). At baseline, high scores of anxiety and depression were recorded (HARS: controls: 33.1+/-7.8, mirtazapine: 33.2+/-12.6, venlafaxine: 36.6+/-5.4; HDRS: controls: 39.5+/-7.4, mirtazapine: 37.9+/-7.8, venlafaxine: 41.9+/-4.5). A marked improvement (p

The objective of the present study was to determine whether a combined psychotherapeutic–psychopharmacological (with mirtazapine) treatment of collateral anxiety and depressive symptomatology during the post-withdrawal phase of alcoholism facilitates the process of alcohol detoxification, which is a decisive stage in the treatment of alcohol-dependent individuals. For that purpose, the rate of remission of anxiety and depressive symptoms over a 4-week detoxification period was evaluated between two groups: the first group followed a standard detoxification protocol ( n = 33) and the second group was assigned to mirtazapine in addition to standard treatment ( n= 35). A marked reduction of anxiety and depressive symptoms was demonstrated in both groups. However, patients on mirtazapine improved more and at a faster rate compared to controls. Thus, mirtazapine, used adjunctively to short-term psychotherapy, may help the detoxification process by minimizing physical and subjective discomfort. Consequently, it may improve patient compliance in alcohol detoxification programs and facilitate the initial phase treatment of alcohol abuse dependence.

ObjectiveClozapine and amisulpride are two effective antipsychotic and their combination often is used for treatment refractory people with schizophrenia, yet many patients partially respond. Clinical data and the recent literature suggest benefits with minocycline. in our study we adjunct minocycline in five schizophrenic patients and we observed them for a period of 6 months.MethodsOur patients received adjunct minocycline (100 mg oral capsule twice daily).ResultsUsing the PANSS, we identified a statistically significant (P < 0.05) clinical improvement from the fourth week of treatment for positive mainly, and less for negative symptoms in all our patients. Global cognitive function did not differ, although there was a significant improvement in working memory favoring minocycline. Moreover there was a marked reduction of anxiety and depressive symptoms.Minocycline was well tolerated and no patient presented side effects.ConclusionMinocycline seems to help significantly schizophrenic patients who do not respond fully to their medication consisted of clozapine and amisulpride. Larger studies are needed to validate these findings.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The alterations of total nitric oxide (NO) (through total nitrite/nitrate) and inducible nitric oxide synthase (iNOS) concentrations were determined in a population of alcohol-dependent individuals without liver disease upon admission for detoxification, two weeks later and after completion of detoxification (4-6 weeks in total).Thirty-eight men and nine women were included in the study. Endogenous nitrite and total nitrite/nitrate concentrations were measured colorimetrically and iNOS concentration was measured by enzyme-linked immunosorbent assay (ELISA).Endogenous and total nitrite concentrations were found to be diagnostically equally conclusive, whereas iNOS values were not correlated with the other two parameters. All three parameters were significantly higher in alcohol-dependent individuals compared to controls at all time points.The preventive therapeutic use of iNOS inhibitors in alcohol-dependent individuals might avoid the injurious effects of chronic alcohol abuse, and should be a matter of further investigation.

The authors report two cases of schizophrenia in which olanzapine proved to be an efficacious antipsychotic medication associated with the remission of movement disorder.

Background GABAergic anticonvulsants have been recommended for the treatment of alcohol dependence and the prevention of relapse. Several studies have demonstrated topiramate's efficacy in improving drinking behaviour and maintaining abstinence. The objective of the present open-label controlled study was to assess efficacy and tolerability of low-dose topiramate as adjunctive treatment in alcohol dependence during the immediate post-detoxification period and during a 16-week follow-up period after alcohol withdrawal. Methods Following a 7-10 day inpatient alcohol detoxification protocol, 90 patients were assigned to receive either topiramate (up to 75 mg per day) in addition to psychotherapeutic treatment (n = 30) or psychotherapy alone (n = 60). Symptoms of depression and anxiety, as well as craving, were monitored for 4-6 weeks immediately following detoxification on an inpatient basis. Thereafter, both groups were followed as outpatients at a weekly basis for another 4 months in order to monitor their course and abstinence from alcohol. Results A marked improvement in depressive (p < 0.01), anxiety (p < 0.01), and obsessive-compulsive drinking symptoms (p < 0.01) was observed over the consecutive assessments in both study groups. However, individuals on topiramate fared better than controls (p < 0.01) during inpatient treatment. Moreover, during the 4-month follow up period, relapse rate was lower among patients who received topiramate (66.7%) compared to those who received no adjunctive treatment (85.5%), (p = 0.043). Time to relapse in the topiramate augmentation group was significantly longer compared to the control group (log rank test, p = 0.008). Thus, median duration of abstinence was 4 weeks for the non-medicated group whereas it reached 10 weeks for the topiramate group. No serious side effects of topiramate were recorded throughout the study. Conclusions Low-dose topiramate as an adjunct to psychotherapeutic treatment is well tolerated and effective in reducing alcohol craving, as well as symptoms of depression and anxiety, present during the early phase of alcohol withdrawal. Furthermore, topiramate considerably helps to abstain from drinking during the first 16-week post-detoxification period.

The need for sensitive biological markers to detect and prove recent drinking has been the focus of many research groups. The aim of our study was to investigate the alterations of biological markers in a population of alcohol dependent individuals during the detoxification period.Fifty-two alcohol-dependent individuals were admitted for alcohol detoxification on an inpatient basis. Carbohydrate-deficient transferrin (CDT), gamma-glutamyl transpeptidase (gamma-GT), interleukin-6 (IL-6), mean corpuscular volume (MCV), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) were obtained at admission and on a 15-day basis. Comparisons between measures were made with t-test.All biochemical parameters associated with alcoholism, with the exception of MCV, were statistically significantly decreased during the detoxification process (p0.05).CDT is an excellent marker of alcohol overconsumption during evaluation, as well as during the detoxification treatment. IL-6 could serve as an additional marker to CDT, a point needing further investigation.

Wernicke-Korsakoff syndrome (WKS) is a neuropsychiatric condition which results from thiamine deficiency, most commonly due to alcohol abuse. The prognosis of WKS is poor and its outcome depends mainly on prompt treatment.A 52-year-old male with a ten-year history of heavy alcohol abuse was admitted in hospital and treated for WKS. Ataxic and oculomotor symptoms promptly reversed following standard treatment but no change was observed in higher mental functioning. Although the protracted WK symptoms made the patient's improvement unlikely, aggressive treatment with thiamine (600 mg/day orally and 300 mg/day intramuscularly) fully reversed the condition within two months.Even though prolongation of undertreatment of WKS typically precludes significant improvement of symptoms due to irreversible damage of the brain, at least in some cases, higher thiamine doses (over 500 mg/day) for a longer period (at least three months) than usually recommended should be tried.

Catatonia is characterized by the predominance of psychomotor abnormalities and shares many clinical, biological and treatment response features with the neuroleptic malignant syndrome (NMS), a rare adverse reaction to psychoactive medications. It has been advocated that the two conditions should be placed along the same spectrum of disorders. A case of a 49-year-old woman, who developed NMS while on low dose clozapine soon after recovering from catatonia, is presented. The potential relationship between catatonia and NMS is discussed in the light of the existing literature, and attention is drawn to the risk for clozapine-induced NMS in catatonic patients.

Materials and methods The sample of the study comprised 200 Caucasian, Greek nationality patients (147 males, 53 females) randomly selected over a 3-year period, who fulfilled the DSM-IV diagnostic criteria for alcohol abuse/dependence, treated on an inpatient basis at the specialized drug and alcohol addiction service of the Athens University Psychiatric Clinic at the Eginition Hospital. Detoxification treatment was comprised of vitamin replacement (vitamin B complex, vitamin C, vitamin E) and oral administration of diazepam (30-60 mg daily in divided doses), with a gradual taper off over a week. Subjects were assessed with the Pilowski scale for hypochondria, the Leyton scale for obsessive-compulsive symptoms and the Sifneos scale for alexithymia. The questionnaires were administered at the beginning of the detoxification period and at discharge. Descriptive statistics are used for the presentation of results.

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.

Genetic factors may influence the liability to treatment outcome and medical complications in alcoholism. In the present study we investigated the IL-1A rs1800587, IL-1B rs3087258, TNF-alpha rs1799724 and the HTTLPR variants in a sample of 64 alcohol dependents and 47 relatives versus a set of clinical parameters and outcome measures. Alcohol dependents had a less favorable clinical profile compared to relatives (higher cholesterol, triglycerides, glucose, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyltransferase). After detoxification, all clinical indexes improved and hepatic enzyme levels were similar in alcohol dependents and relatives, except for the GGT that remained significantly higher in alcohol dependents. Alcoholic depressive and anxiety scores were significantly reduced after detoxification. IL-1A, IL-1B, TNF-alpha and HTTLPR variants were not associated with any baseline clinical index or change after detoxification. In our sample IL-1A, IL-1B, TNF-alpha and HTTLPR do not appear as liability factors for alcohol toxicity or detoxification outcome, however the small sample size may influence the observed results.

Background Several studies indicate that patients with comorbid alcohol dependence and affective syndromes can be differentiated on the basis of the time of onset of mood symptoms relative to alcohol abuse. However, there are limited data on the underlying pathogenetic mechanisms and risk factors that differentiate between primary and secondary affective disorders (AD) in the context of alcohol dependence. In the present study we investigated the sociodemographic characteristics, family history and the course of illness in cases of comorbid alcohol dependence and AD.

none

Background: Social anxiety disorder is fairly prevalent among alcohol abusing/dependent subjects. The objective of the present study was to investigate: (a) the incidence of social anxiety symptoms in inpatient alcoholics, (b) the effect of alcohol detoxification on these symptoms, and (c) whether a combined psychotherapeutic/mirtazapine treatment during the post-detoxification phase of alcoholism has a greater impact on the aforementioned symptoms than a non-pharmacological approach. Method: Social anxiety symptoms were assessed through the Liebowitz Social Anxiety Scale (LSAS) following a 4–5-week detoxification period in two groups: group A (n=21) that followed a detoxification protocol of cognitive–behavioral orientation and group B (n=33) that was assigned to mirtazapine in addition to the standard protocol. Concomitant psychopathology was monitored through the HARS and HDRS, and level of functioning through the GAS. Results: A marked reduction of social anxiety symptoms was evidenced in both groups. However, patients on mirtazapine improved significantly more compared to controls. Limitations: A single measure of social anxiety, i.e., the LSAS was used. Also, a longer follow-up period is needed to ascertain remission of social anxiety symptoms. Conclusions: The present study found a rather high incidence of social anxiety symptoms in inpatient alcoholics which subsided following alcohol detoxification; moreover, it provides preliminary evidence that a combined psychotherapeutic/mirtazapine treatment (30–60 mg/daily) has a greater impact on the aforementioned symptoms than non-pharmacological treatment alone.