Alcohol-related peripheral neuropathy: Clinico-neurophysiological characteristics and diagnostic utility of the neuropathy symptoms score and the neuropathy impairment score.

Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available.

Elevated liver enzymes and fasting glucose levels correlate with neuropathy in patients diagnosed with alcohol use disorder independently of the blood thiamine levels.

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.

Effects of a Two-Month Exercise Training Program on Concurrent Non-Opiate Substance Use in Opioid-Dependent Patients during Substitution Treatment.

BACKGROUND: This randomized controlled trial aimed to evaluate the effects of a two-month exercise intervention on the concurrent non-opiate substance use (alcohol, cocaine, cannabis, and benzodiazepines) in opioid users during their medication treatment. METHODS: Ninety opioid users (41 females) in methadone and buprenorphine medication treatment were randomly divided into four groups: (a) buprenorphine experimental (BEX; n = 26, aged 41.9 ± 6.1 yrs); (b) buprenorphine control (BCON; n = 25, aged 41.9 ± 5.6 yrs); (c) methadone experimental (MEX; n = 20, aged 46.7 ± 6.6 yrs); and (d) methadone control (MCON; n = 19, aged 46.1 ± 7.5 yrs). The experimental groups (BEX and MEX) followed an aerobic exercise training program on a treadmill for 20 min at 70% HRmax, 3 days/week for 8 weeks. Socio-demographic, anthropometric, and clinical characteristics, as well as non-opioid drug use in days and quantity per week, were assessed before and after the intervention period. RESULTS: Following the exercise training, the weekly non-opioid substance consumption (days) decreased (p < 0.05) in both exercise groups and was lower in BEX compared to MEX, while no differences were observed (p > 0.05) between the control groups (BCON vs. MCON) or compared to their baseline levels. Similarly, the daily amount of non-opiate substance intake was reduced (p < 0.05) post-training in BEX and MEX, whereas it did not differ (p > 0.05) in BCON and MCON compared to the baseline. CONCLUSIONS: The two-month exercise intervention reduced the non-opioid drug use in both the methadone and buprenorphine substitution groups compared to the controls, suggesting that aerobic exercise training may be an effective strategy for treating patients with OUDs.

Pure small fiber neuropathy in alcohol dependency detected by skin biopsy.

BACKGROUND: Alcohol overconsumption is well known to cause damage to the peripheral nervous system. The aim of this study was the functional and structural evaluation of the small nerve fibers in alcohol-dependent subjects, with or without symptoms of peripheral neuropathy. METHODS: Twenty-six consecutive alcohol-dependent subjects treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic were enrolled in this prospective study over 18 months. Every subject was assessed by peripheral nerve evaluation using the Neuropathy Symptoms Score (NSS) and Neuropathy Impairment Score (NIS), followed by nerve conduction studies (NCS), quantitative sensory testing (QST), and skin biopsy. Twenty-nine normal subjects, age- and gender-matched, constituted the control group. RESULTS: Peripheral neuropathy was diagnosed in 16 subjects (61.5%). Among these 16 subjects, pure large fiber neuropathy (LFN) was found in two subjects (12.5%), pure small fiber neuropathy (SFN) was found in eight subjects (50%), and both large and small fiber neuropathy was diagnosed in six patients (37.5%). The intraepidermal nerve fiber density (IENFD) of the patients' skin biopsy was significantly lower than that of the control group. Additionally, QST results showed a statistically significant sensory impairment in the patients. CONCLUSIONS: Our study confirms small fiber neuropathy due to alcohol abuse with a high prevalence of pure SFN that might have remained undetected without QST and IENFD.

Development and validation of the Schedule for the Assessment of Insight in Alcohol Dependence (SAI-AD): Dimensions and correlates of insight in alcohol use disorder.

INTRODUCTION: The objectives of this study were to develop a multidimensional, clinician-rated scale that assess impaired insight into illness in patients with alcohol use disorder (AUD) and to examine its reliability, validity and internal structure. Moreover, we investigated the relationships of overall insight and its dimensions with demographic and clinical characteristics in AUD. METHODS: We developed the Schedule for the Assessment of Insight in Alcohol Dependence (SAI-AD), based on scales that has already been used in psychosis and other mental disorders. Sixty-four patients with AUD were assessed with SAI-AD. Hierarchical cluster analysis and multidimensional scaling were used to identify insight components and assess their inter-relationships. RESULTS: The SAI-AD demonstrated good convergent validity (r = -0.73, p < 0.001) and internal consistency (Cronbach's alpha = 0.72). Inter-rater and test-retest reliabilities were high (intra-class correlations 0.90 and 0.88, respectively). Three subscales of SAI-AD were identified which measure major insight components: awareness of illness, recognition of symptoms and need for treatment, and treatment engagement. Higher levels of depression, anxiety and AUD symptom severity were associated with overall insight impairment but not with recognition of symptoms and need for treatment, or with treatment engagement. Illness duration was specifically and positively associated with the treatment engagement component of insight. CONCLUSIONS: Insight is a multidimensional construct in AUD and its major components appear to be associated with different clinical aspects of the disorder. The SAI-AD is a valid and reliable tool for the assessment of insight in AUD patients.

The Role of Physical Exercise in Opioid Substitution Therapy: Mechanisms of Sequential Effects.

It is generally accepted that chronic opioid use is associated with structural and functional changes in the human brain that lead to an enhancement of impulsive behavior for immediate satisfaction. Interestingly, in recent years, physical exercise interventions have been used as an adjunctive treatment for patients with opioid use disorders (OUDs). Indeed, exercise has positive effects on both the biological and psychosocial basis of addiction, modifying neural circuits such as the reward, inhibition, and stress systems, and thus causing behavioral changes. This review focuses on the possible mechanisms that contribute to the beneficial effects of exercise on the treatment of OUDs, with emphasis placed on the description of a sequential consolidation of these mechanisms. Exercise is thought to act initially as a factor of internal activation and self-regulation and eventually as a factor of commitment. This approach suggests a sequential (temporal) consolidation of the functions of exercise in favor of gradual disengagement from addiction. Particularly, the sequence in which the exercise-induced mechanisms are consolidated follows the pattern of internal activation-self-regulation-commitment, eventually resulting in stimulation of the endocannabinoid and endogenous opioid systems. Additionally, this is accompanied by modification of molecular and behavioral aspects of opioid addiction. Overall, the neurobiological actions of exercise in combination with certain psychological mechanisms appear to promote its beneficial effects. Given the positive effects of exercise on both physical and mental health, exercise prescription is recommended as a complement to conventional therapy for patients on opioid maintenance treatment.

Internet gaming disorder, exercise and attention deficit hyperactivity disorder: The role of symptoms of depression, anxiety and stress.

One of the issues that have risen the past few decades due to excessive use of technological advances is internet gaming disorder (IGD). Past research has concluded that there is a negative association between IGD and exercise as well as a positive association between IGD and attention deficit hyperactivity disorder (ADHD). However, the existing studies on these subjects are scarce. Furthermore, researchers have showcased that symptoms of depression, anxiety and stress are positively associated with IGD and ADHD but negatively associated with exercise. Consequently, maybe these symptoms mediate the relationships between IGD, exercise and ADHD. The purpose of the present study is to investigate the relationship between IGD and exercise as well as between IGD and ADHD. A correlational study was conducted on 515 adults through Google forms. The Internet Gaming Disorder Scale-Short-Form was used to detect IGD symptoms, the Leisure-Time Exercise Questionnaire was utilized so as to evaluate participants' leisure - time exercise habits, and the Barkley Adult ADHD Rating Scale was used to assess ADHD symptoms. Furthermore, the Depression, Anxiety and Stress Scale-21 was utilized to evaluate symptoms of depression, anxiety, and stress. It was found that there is a negative correlation between IGD symptoms and leisure time exercise as well as a positive correlation between IGD symptoms and ADHD symptoms. Moreover, when taking all the variables that were examined into consideration, it was indicated that inattention symptoms and impulsivity symptoms were significantly associated with IGD symptoms whereas symptoms of depression were partially and significantly mediating the association between IGD symptoms and Attention deficit as well as the association between IGD symptoms and Impulsivity. The findings of the current study suggest that people who deal with IGD symptoms tend to exercise less on their free time. Additionally, people with more IGD symptoms display not only more ADHD symptoms, symptoms of inattention and impulsivity specifically, but also more symptoms of depression. Therefore, clinicians should evaluate the possible coexistence of such symptoms when treating people with IGD, in order to prevent as well as treat more efficiently IGD and its consequences.

Substance use during the COVID-19 pandemic: What is really happening?

The COVID-19 pandemic is associated with increased levels of anxiety, fear, sadness, difficulty adjusting, symptoms of post-traumatic stress disorder and suicidality, both in the general population and specific subgroups. The presence of this type of psychopathology increases the risk of involvement with or worsens the use of addictive substances and alcohol as a maladaptive coping strategy.1 According to these data, people with substance use disorders are a population at high risk for COVID-19 infection and serious illness. Α large controlled retrospective case study in the US found that people with substance use disorders are significantly more vulnerable to COVID-19 and its complications (primarily those with opioid use disorder OR = 10.21 and with tobacco use disorder OR = 8.25), and that the course and outcome of the disease (hospitalization, death) was worse than in non-dependent individuals. The main culprits are increased physical co-morbidity (frequent respiratory and cardiovascular problems), poor health and living conditions, marginalization and difficulties in accessing health services. 2,3 Ιnternational epidemiological data during the first months of the pandemic regarding the use of addictive substances do not lead to safe conclusions. A cross-sectional online epidemiological study conducted on a sample of 36,538 adults from 21 European countries between April and July 2020 found an overall decrease in alcohol use, which was mainly attributed to the reduction of heavy episodic consumption, while at the same time an increase in alcohol consumption among people with severe alcohol use was recorded. Τhe use of cannabis and nicotine showed increasing trends, as well as the use of cocaine, but to a lesser extent, while the use of MDMA (ecstasy) showed a decrease.4 In a review of 45 cross-sectional studies conducted between December 2019 and November 2020, alcohol use was on the rise overall, despite geographical variations, as was the use of other addictive substances, cannabis in particular.5 It should be noted that those who increased alcohol use during quarantine were those exhibiting higher levels of negative emotionality mechanisms.6 In Greece, an online cross-sectional survey in April 2020 in the general population during the first lockdown showed a reduction in alcohol use (43.7% of alcohol users reduced or quit), a reduction in cannabis (67.3% quit), while 33.3% increased nicotine use. These changes were attributed to the limitation of alcohol availability, social distancing, changes in daily routine and income reduction.7,8 Also, wastewater samples from Athens, analyzed by the Laboratory of Analytical Chemistry of EKPA, showed a significant increase in the use of cocaine (67%), amphetamine (350%) and methamphetamine (37%), and a decrease in the use of MDMA (- 38%) during the first lockdown, compared to the corresponding period of the previous year.9 Analysis of wastewater samples from other European cities "suggest that levels of use of most drugs appear generally lower during the initial lockdowns, but then appear to bounce back once lockdown was lifted. A comparison with 2019 appears to suggest similar overall consumption of most drugs, and in several cities possibly even higher levels, based on this data source. Exceptions here appear to be MDMA and methamphetamine, two drugs for which the levels observed in 2020 appear lower in most of the participating cities".10,11 There were also changes in the locations of use of the substances, as with the periodic restrictions the use was transferred mainly at home and in open public spaces; in some cases, it was associated with increased intravenous use and cases of intoxication. Finally, intermittent difficulties in drug availability and trafficking have led users to search for other substances, increase experimentation and multidrug use, and make online purchases. In addition, there is concern about the increasing abuse of benzodiazepines, which are either diverted from therapeutic use or appear on the illicit market, often as new benzodiazepines.10,12 According to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), "the drug market has been remarkably resilient to disruption caused by the pandemic" … Drug trafficking has adapted to the new conditions with changes in routes and methods of trafficking, and by further enhancing the digital presence of the drug market… "Any reductions in drug consumption seen during the initial lockdowns rapidly disappeared as social distancing measures were eased. In general terms, there appears to have been less consumer interest in drugs usually associated with recreational events, such as MDMA, and greater interest in drugs linked with home use. However, the easing of restrictions … during the summer was associated with a rebound in the levels of use". Also, "survey data suggest that those using drugs occasionally prior to COVID-19 may have reduced or even ceased their use during the pandemic, but more-regular users may have increased their drug consumption".10 Measures taken to control the pandemic have reduced and modified the mental health and addiction treatment services provided. Although services have been adequately restored, there has initially been a 60% reduction in the availability and provision of detoxification services in Europe.13 Live contact, mainly at group level, was significantly reduced or stopped altogether for a long period, as well as the frequency of individual appointments. Therapeutic programs sought to respond to the new conditions using technology and telemedicine, providing online group support and psychotherapy. Substitution treatment programs have become more flexible by providing long-term pharmaceutical substitutes (take home) to prevent users from moving. There have also been facilitations in prescribing by treating physicians. Thus, the addicts' contact with the treatment process was maintained, but it was insufficient to meet their increased needs during this period. In conclusion, it should be noted that substance use appears to have an autonomous dynamism in relation to the pandemic and the consequent psychopathology, being in a "loose" causal relationship with it. Therefore, hasty and untimely generalizations should be avoided, and easy conclusions should not be drawn through extrapolations from previous socio-economic crises of different types or through partial spatiotemporal understandings, which are usually presented by the media in the form of negative alarming information.

New-Onset Psychosis Associated With a Lesion Localized in the Rostral Tectum: Insights Into Pathway-Specific Connectivity Disrupted in Psychosis.

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.

Coping and Its Relation to PTSD in Greek Firefighters.

Firefighters are exposed continuously to intense stress situations and traumatic incidents, and are at high risk of developing posttraumatic stress disorder (PTSD). Coping mechanisms and behaviors have been examined as factors contributing to PTSD. The strategies that may be used to cope with stress and/or trauma differ between individuals and also between different professions and traumatic events (). Although there is a vast literature on stress and coping processes that exists, very few studies investigated the way individual firefighters cope with trauma. Among several questionnaires that have been used to examine the effects of different types of coping mechanisms after traumatic incidents is the Albert Einstein College of Medicine-Coping Style Questionnaire (AECOM-CSQ; ). In August 2007, large areas in the Peloponnese, Greece, were devastated by wildfires. One month after the event, experienced researchers visited the affected area to provide psychological support and to investigate the psychosocial consequences among the local professional firefighters. One hundred two firefighters that were on duty for the entire period of firefighting (several days) were interviewed using several questionnaires, among them the AECOM-CSQ. Our hypothesis was that firefighters who presented with PTSD would be more inclined toward engaging in avoidance coping mechanisms. A total of 18.6% of the firefighters were found to have PTSD according to ICD-10 criteria. Logistic regression showed that firefighters using the coping mechanisms of minimization and blame were associated with the greater likelihood of PTSD. It seems that specific coping mechanisms used by firefighters immediately after the traumatic event might contribute to the development of PTSD.

Quality of sleep in renal transplant recipients and patients on hemodialysis.

BACKGROUND: Sleep disorders are very common in patients with chronic kidney disease and they may not always subside after kidney transplantation. AIM AND METHODS: The aim of this cross-sectional study was to evaluate the self-reported quality of sleep, insomnia problems in particular, and examine the factors that disturb sleep of kidney transplant recipients (KTx: n=152) in comparison to age- and sex-matched patients on dialysis (HD: n=67) and participants with normal renal function (NOR: n=49), through the administration of the Athens Insomnia Scale (AIS) at least six months after transplantation. Clinical and laboratory data, as well as health-related quality of life, depression, anxiety, post-traumatic stress symptoms, and the presence of restless legs syndrome (RLS) and pruritus were investigated in relation to sleep problems. RESULTS: The highest mean AIS score was observed in the transplant patients (KTx: 4.6±13.3 vs. HD: 3.8±8.1 vs. NOR: 2.4±10.2); both KTx and HD patients had a lower quality of sleep compared to participants with normal renal function. Multiple linear regression analysis showed that the determinants of the total AIS score were the frequency of post-traumatic stress symptoms, depression, RLS, diastolic blood pressure, and pain (all p<0.0001). CONCLUSION: Although amelioration of renal function post-transplantation improves several aspects of quality of life, it does not seem to have a beneficial effect on self-reported sleep.

Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled Trial.

OBJECTIVES: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear. METHODS: We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less. RESULTS: Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission. CONCLUSIONS: Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.

Alteration of α-N-acetylgalactosaminidase (nagalase) concentration in alcohol-dependent individuals without liver disease, during the detoxification therapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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-value<0.001). 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. CONCLUSIONS: 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.

Alteration in the concentrations of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) in alcohol-dependent individuals without liver disease, during detoxification therapy.

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.

EEG-based investigation of brain connectivity changes in psychotic patients undergoing the primitive expression form of dance therapy: a methodological pilot study.

Primitive expression (PE) is a form of dance therapy (DT) that involves an interaction of ethologically and socially based forms which are supplied for re-enactment. There exist very few studies of DT applications including in their protocol the measurement of neurophysiological parameters. The present pilot study investigates the use of the correlation coefficient (ρ) and mutual information (MI), and of novel measures extracted from ρ and MI, on electroencephalographic (EEG) data recorded in patients with schizophrenia while they undergo PE DT, in order to expand the set of neurophysiology-based approaches for quantifying possible DT effects, using parameters that might provide insights about any potential brain connectivity changes in these patients during the PE DT process. Indication is provided for an acute potentiation effect, apparent at late-stage PE DT, on the inter-hemispheric connectivity in frontal areas, as well as for attenuation of the inter-hemispheric connectivity of left frontal and right central areas and for potentiation of the intra-hemispheric connectivity of frontal and central areas, bilaterally, in the transition from early to late-stage PE DT. This pilot study indicates that by using EEG connectivity measures based on ρ and MI, the set of useful neurophysiology-based approaches for quantifying possible DT effects is expanded. In the framework of the present study, the causes of the observed connectivity changes cannot be attributed with certainty to PE DT, but indications are provided that these measures may contribute to a detailed assessment of neurophysiological mechanisms possibly being affected by this therapeutic process.

Vasomotor and depression symptoms may be associated with different sleep disturbance patterns in postmenopausal women.

OBJECTIVE: This study aims to explore the association of vasomotor symptoms (VMS) and depression symptoms with different symptoms of subjective sleep disturbance in postmenopausal women. METHODS: This is a cross-sectional study of 163 postmenopausal women (not taking hormone therapy) attending a university menopause clinic. Measures included the Athens Insomnia Scale, Greene Climacteric Scale, and Symptom Checklist-90-Revised depression subscale. Covariate-adjusted ordinal logistic regression was used to investigate the association of VMS and depression with each item of the Athens Insomnia Scale. RESULTS: Controlling for confounding factors, we found VMS to be significantly associated with awakenings during the night (odds ratio [OR], 1.85; P < 0.001), overall quality of sleep (OR, 2.00; P < 0.001), well-being during the day (OR, 1.63; P = 0.008), functioning capacity during the day (OR, 1.72; P = 0.01), and sleepiness during the day (OR, 1.66; P = 0.03); whereas we found Symptom Checklist-90-Revised depression subscale scores to be associated with sleep induction (OR, 2.09; P < 0.001), final awakening earlier than desired (OR, 2.21; P < 0.001), total sleep duration (OR, 1.62; P = 0.01), overall quality of sleep (OR, 1.64; P = 0.009), well-being during the day (OR, 1.67; P = 0.006), functioning capacity during the day (OR, 1.68; P = 0.01), and sleepiness during the day (OR, 1.57; P = 0.04). CONCLUSIONS: VMS and depression symptoms are associated with different patterns of sleep disturbance. Although both symptoms are related to sleep quality, daytime functioning, and daytime well-being, depression is uniquely associated with difficulty falling asleep and waking up earlier than desired, whereas VMS are related to frequent awakenings during sleep. The findings are limited by the cross-sectional design and relatively small sample size of the study. Recommendations for future research are discussed to guide this line of inquiry and to gain a better understanding of the complex relationship between climacteric and mood symptoms and their contribution to the development of sleep disturbances during menopause.

Sleep EEG and spindle characteristics after combination treatment with clozapine in drug-resistant schizophrenia: a pilot study.

PURPOSE: Clozapine is an atypical neuroleptic agent, effective in treating drug-resistant schizophrenia. The aim of this work was to investigate overall sleep architecture and sleep spindle morphology characteristics, before and after combination treatment with clozapine, in patients with drug-resistant schizophrenia who underwent polysomnography. METHODS: Standard polysomnographic techniques were used. To quantify the sleep spindle morphology, a modeling technique was used that quantifies time-varying patterns in both the spindle envelope and the intraspindle frequency. RESULTS: After combination treatment with clozapine, the patients showed clinical improvement. In addition, their overall sleep architecture and, more importantly, parameters that quantify the time-varying sleep spindle morphology were affected. Specifically, the results showed increased stage 2 sleep, reduced slow-wave sleep, increased rapid eye movement sleep, increased total sleep time, decreased wake time after sleep onset, as well as effects on spindle amplitude and intraspindle frequency parameters. However, the above changes in overall sleep architecture were statistically nonsignificant trends. CONCLUSIONS: The findings concerning statistically significant effects on spindle amplitude and intraspindle frequency parameters may imply changes in cortical sleep EEG generation mechanisms, as well as changes in thalamic pacing mechanisms or in thalamo-cortical network dynamics involved in sleep EEG generation, as a result of combination treatment with clozapine. SIGNIFICANCE: Sleep spindle parameters may serve as metrics for the eventual development of effective EEG biomarkers to investigate treatment effects and pathophysiological mechanisms in schizophrenia.

NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture.

Frontotemporal dementia (FTD) is increasingly becoming recognized as a major cause of early onset (<65 years) neurodegenerative dementia. Although sleep disorders significantly impair patients' and caregivers' quality of life in neurodegenerative diseases, polysomnographic data in FTD patients are scarce in literature. Aim of our study was to investigate sleep microstructure in FTD, by means of Cyclic Alternating Pattern (CAP), in a group of ten behavioral variant FTD patients (6 M, 4 F; mean age 61.2±7.3 years; disease duration: 1.4±0.7 years) and to compare them with cognitively intact healthy elderly. Sleep in FTD patients was altered at different levels, involving not only the conventional sleep stage architecture parameters (total sleep time, single stage percentage, NREM/REM cycle organization), but also microstructure. FTD subjects showed CAP disruption with decreased slow wave activity related phases (A1 index, n/h:14.5±6.8 vs 38.8±6.6; p<.001) and increased arousal-related fast CAP components (A2 index 22.9±8.2 vs 11.6±3.7; p=.006; A3 index 41.9±20.7 vs 13.0±6.5; p=.002). Several correlations between sleep variables and neuropsychological tests were found. Sleep impairment in FTD may be specifically related to the specific frontal lobe involvement in the neurodegenerative process. The pattern of alterations seems somewhat peculiar, probably due to the anatomical distribution of the neurodegenerative process with a major impact on frontal lobe generated sleep transients, and a substantial sparing of phenomena related to the posterior cortex.

Total nitric oxide and inducible nitric oxide synthase in alcohol-dependent individuals during detoxification therapy.

BACKGROUND: 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). MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.