Massimiliano Pomponi

Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor

Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

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.

Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers.

Chronic cannabis use produces effects within the central nervous system (CNS) which include deficits in learning and attention tasks and decreased brain volume. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are proteins that serve as survival factors for CNS neurons. Deficits in the production and utilization of these proteins can lead to CNS dysfunctions including those associated with cannabis abuse. In this study we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF serum levels in two groups of subjects: cannabis-dependent patients and healthy subjects. We found that NGF serum levels were significantly reduced in cannabis abusers as compared to healthy subjects. These findings indicate that NGF may have a role in the central action of cannabis and potentially in the neurotoxicity induced by this drug. These data also suggest that chronic cannabis consumption may be a risk factor for developing psychosis among drug users.

What is the effect of selective serotonin reuptake inhibitors on temperament and character in patients with fibromyalgia

OBJECTIVE The purpose of the present study was to assess a group of patients with fibromyalgia (FM) and control subjects using the personality questionnaire proposed by Cloninger and to determine possible changes in the Italian version of the Temperament and Character Inventory-Revised patterns of patients with FM after therapy with serotoninergic antidepressants (selective serotonin reuptake inhibitors [SSRIs]). METHODS Sixty patients with FM filled out the Temperament and Character Inventory-Revised and Beck Depression Inventory before and after 6-month therapy with SSRIs (escitalopram 10 mg, fluoxetine 20 mg, or paroxetine 20 mg). A total of 80 age-, sex-, and education level-matched healthy subjects were selected as a control group. RESULTS Both in the pretreatment and posttreatment period, patients were found to have higher harm avoidance and lower self-directedness scores than healthy controls. In addition, harm avoidance and self-directedness were state and trait dependent. CONCLUSIONS Depressive symptoms in patients with FM can be significantly decreased by treatment with SSRIs. A careful clinical assessment and study of personality profile is needed to identify patients with FM who may benefit from antidepressant pharmacologic therapy and specific psychotherapeutic interventions.

Why docosahexaenoic acid and aspirin supplementation could be useful in women as a primary prevention therapy against Alzheimer's disease?

The assumption that disease specific risk factors are similar or the same in men and women may lead to incorrect primary prevention strategies. This study focused on the evaluation of gender-specific Alzheimers disease (AD) risk factors. In AD, female gender appears to be an important risk factor associated with the aberrant production of beta amyloid (βA) peptides. Although decreased levels in plasma DHA concentration are associated with cognitive decline in healthy elderly and Alzheimers patients, pre-treatment with DHA significantly reduced the survival of cortical neurons incubated with beta amyloid (βA). Hence, in the presence of an increasing amount of βA, paradoxically women - who have higher plasma levels of DHA - are more likely to develop AD. Aspirin (ASA) converts cyclooxygenase (COX)-2 into a form that generates new neuroprotective docosanoids from DHA; therefore, ASA might positively resolve the paradoxical effect of the concomitant presence of DHA and βA.

Is Alzheimer's Disease a Synaptic Disorder?

BACKGROUND In Alzheimers disease (AD), the common symptom is loss of memory. Learning and memory are associated with amoeboid movements of synaptic endings. Docosahexaenoic acid (DHA) is a major lipid constituent of synaptic end sites. Minor changes in the fluidity of phospholipidic membranes have a dramatic impact on the function of synapses, where membrane fluidity may influence the neurotransmitter receptor activity. METHOD Studies pertaining to the role of DHA as a neuroprotective agent was reviewed. RESULTS Here we will show a conceptual framework for the role of DHA in the prevention of AD. The DHA content has been shown to be decreased in the brain and plasma of patients affected by AD. Aspirin triggers the generation of DHA-derived mediators that are themselves neuroprotective. CONCLUSION Adequate dietary intakes of the neuroprotective DHA (and aspirin?) may slow down the progression of AD. An essential reserve of synapses from early development is needed.

A case of CMT 1B due to Val 102/fs null mutation of the MPZ gene presenting as hyperCKemia

Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A, due to a duplication in the gene encoding the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P0) account for demyelinating CMT1B. Herein, we report a patient presenting with an isolated hyperCKemia in whom electrophysiological and pathological findings revealed a demyelinating and axonal neuropathy. Sequencing of the MPZ gene revealed a 306delA at codon 102 in the proband and in two relatives. This mutation has been already described in association with paucisymptomatic CMT without hyperCKemia.

Plasma levels of n-3 fatty acids in bipolar patients: Deficit restricted to DHA

Epidemiological studies suggest that n-3 polyunsaturated fatty acid (n-3 FA) deficiency is a risk factor for bipolar disorders (BDs). The aim of this study was to determine whether such a deficit does exist in patients with BD and to characterize the overall plasma fatty acid (FA) profile in these patients. Using gas chromatography/mass spectrometry, we measured fasting plasma levels of 15 FAs in 42 patients diagnosed with BD according to DSM-IV criteria and in 57 age- and gender-matched healthy controls. Plasma docosahexaenoic acid (DHA) levels were significantly decreased in bipolar patients (p < 0.001 versus healthy controls). Compared with controls, patients had higher plasma levels of all other FAs, including arachidonic acid (AA, p < 0.001), alpha-linolenic acid (ALA, p < 0.001), and eicosapentaenoic acid (EPA) (p < 0.001). Although in the present study we observed significant DHA deficits in the plasma of bipolar patients our findings do not support the therapeutic use of ALA and/or EPA supplementation. DHA may provide a basis for possible pharmacological intervention in psychiatric disorders at the level of second messengers linked to the phosphatidylinositol cycle. Finally, measurement of FA levels in plasma seems to be more reliable and reproducible than assays of erythrocyte FA content.

Impulsive compulsive behaviours in Parkinson's disease: patients' versus caregivers' perceptions.

Impulsive compulsive behaviours (ICB) are neuropsychiatric disorders that can complicate Parkinson’s disease (PD). ICB include pathological gambling, compulsive sexual behaviour, compulsive buying, and binge eating, together with punding and dopamine dysregulation syndrome [1]. The PD Impulsive-Compulsive Disorders Questionnaire (QUIP) is a validated instrument to assess the presence of ICB in PD [2, 3]. A recent study has showed that the QUIP scale is a sensitive instrument whether completed by the patients or by their informants and that when comparing the QUIP completed by the patients to the one completed by their informant, the patient/informant agreement in referring the presence of ICD was moderate [4]. Here we describe our experience and we aimed to evaluate the patients and their carers’ agreement in reporting the presence of ICB. Forty-six patients and their carers were evaluated before attending a conference on non-motor symptoms in PD held by experts in the matter. They all agreed to participate, provided informed consent and were included in the study. Patient’s demographical and clinical data were collected. Patients and their carers were asked to complete the QUIP separately and they were instructed to refer to patient’s behaviour in the past year, considering behavioural changes lasting for at least four consecutive weeks. We performed statistical analysis by means of SPSS version 21 (Statistical Package for Social Science). The degree of agreement between each patient and his/her carer was calculated using the Cohen’s K. Forty-six patients (37 % females; mean age 66.4 years, SD 7.4 years, range 47–78 years; disease duration 6.16 years, SD 2.97 years, range 2–14 years; mean Levodopa equivalent daily dose 698.8, SD 375.8) and 46 carers (63 % females; mean age 63.2 years, SD 8.3 years, range 45–76 years) were included in the study. The prevalence of compulsive gambling, sexual behaviour, buying, eating, hobbyism/punding, walkabout and medication overuse according to patients’ and their carers’ QUIPs are shown in Table 1. According to patients’ QUIP, 31 patients (67.3 %) reported the presence of at least one ICB. The same percentage was found analysing carers’ QUIP. The degree of agreement between each patient and his/ her carer was then calculated. We found 26 couples to have poor agreement (Cohen’s K\ 0.41) (Table 1). Within these 26 couples where the agreement was poor, we analysed the single sub-items of the QUIP to define for each couple: (a) for which item there was a poor agreement; and (b) in which direction was the disagreement (patient saying ‘yes’, caregiver ‘no’ or vice versa) (Table 1). In the 26 couples where the agreement was poor, patients tend to report more often than carers the presence of compulsive sexual behaviour, hobbyism/punding, walkabout and medication overuse. Viceversa compulsive gambling, buying and eating were more reported by caregivers than patients. The lowest degree of agreement was found for compulsive eating and hobbism/punding. & B. Demartini bennidemartini@hotmail.it

Maternal Fish Oil Supplementation: The Prodrom of Synaptic Protection in Alzheimers Disease

Prospective longevity is overshadowed by the high prevalence of mental decline in aging. Hence, nutritional indications are a crucial element in todays observed aging of the population. There is now growing epidemiological evidence suggesting that reduced levels of docosahexaenoic acid [DHA, 22:6, (n-3)] may be indicative of an increased risk of Alzheimers disease (AD). On the other hand, the Mediterranean diet includes high intake of fatty fish and has been associated with lower AD risk; fish is the major food source of DHA. Recently three new families of DHA-derived mediators - termed D series resolvins (RvDs, 17S epimers), protectins (NPDs, 17S epimers) and maresins - have been uncovered; these new bioactive lipids confer potent cellular protection. In the presence of aspirin (ASA), equipotent ASA-triggered 17R epimers (ASA-RvDs and ASA-NPDs) were produced in vivo. However, while enzymatic oxidation dramatically reduced the bioactivity of 17S epimers RvDs and NPDs, enzymatic conversion of ASA-17R epimers was sharply reduced. Specifically, as ASA-DHA-derived lipids have cellular protective actions, the resistance to rapid inactivation may contribute to the beneficial actions of omega-3 (n-3) fish oils and ASA in humans and offers new insights into the prevention of neurodegenerative diseases.