Relationship between craving and plasma leptin concentrations in patients with cocaine addiction.

BACKGROUND: There is robust evidence indicating an overlap between neurobiological circuitry and pathways that regulate addictions and those that regulate appetite and food intake. Rodent work suggests a role of the appetitive peptide leptin in cocaine-seeking behaviours. The goal of this study was to investigate the possible relationship between plasma leptin concentrations and cocaine craving and use in patients seeking treatment for cocaine dependence. METHODS: Patients (N=43) with a DSM-IV diagnosis of cocaine dependence were studied before starting detoxification (baseline; T0) and then again 14days after (T1; only those patients who abstained from cocaine during the study). Blood samples for plasma leptin concentrations were collected and cocaine craving was assessed using the Brief Cocaine Craving Questionnaire (Brief-CCQ). Food craving was also assessed using a food Visual Analogue Scale (f-VAS). Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity. RESULTS: Plasma leptin concentrations at T0 significantly correlated with baseline Brief-CCQ scores (r=0.34, p<0.05). Furthermore, plasma leptin concentrations at T1 significantly correlated with the baseline amount of cocaine used (r=0.5, p<0.05). There were no significant correlations between plasma leptin concentrations and f-VAS scores either at T0 or T1 (p's>0.05). CONCLUSIONS: The present study suggests a potential relationship between plasma leptin concentrations and cocaine craving and use. Future mechanistic studies are needed to determine whether manipulations of leptin signalling may lead to novel pharmacological approaches to treat cocaine addiction.

Neural correlate of Internet use in patients undergoing psychological treatment for Internet addiction.

BACKGROUND: The new version of Diagnostic and Statistical Manual of Mental Disorders (DSM-5th) proposed the Internet Gaming Disorder for the diagnosis of Internet addiction (IA) considering the neurobiological evidence of the craving. AIMS: The aim was to test the neural correlate in response to the Internet cue in patients with IA. METHODS: Sixteen males with IA diagnosis (clinical group) and 14 healthy male (control group) were recruited for an experimental visual task composed of Internet images and emotional images. During the visual presentation of Internet cue, electroencefalographic data were recorded using Net Station 4.5.1 with a 256-channels HydroCel Geodesic Sensor Net. Event-related potential (ERP) components and low-resolution electromagnetic tomography (sLoreta) were analysed. RESULTS: sLoreta analyses showed that patients from the clinical group presented a higher primary somatosensorial cortex and lower paralimbic, temporal and orbito-frontal activation in response to both Internet and emotional images compared to those of the control group. CONCLUSIONS: These results suggest that clinically recognized pathological use of Internet could be linked to dissociative symptoms.

Is Internet addiction a psychopathological condition distinct from pathological gambling?

AIMS: The behavioural-addiction perspective suggests that Internet addiction (IA) and pathological gambling (PG) could share similar characteristics with substance dependence. Despite the similarities between IA and PG, it is not clear whether these disorders share different or similar psychopathological conditions. The aim of the present study was to test whether IA patients presented different psychological symptoms, temperamental traits, coping strategies and relational patterns compared with PG patients. The hypothesis was that IA patients will show greater interpersonal disengagement than PG patients. METHODS: Two clinical groups (31 IA patients and 11 PG patients) and a control group (38 healthy subjects) matched with the clinical groups for gender and age were enrolled. The clinical groups were gathered in a psychiatric service for IA and PG in a hospital. Anxiety, depression, coping strategies, attachment, temperament, and global assessment of functioning were measured. MANOVAs, ANOVAs and post-hoc comparisons were carried out in order to test the hypothesis. RESULTS: Despite IA and PG showing similar differences with the control group on the levels of depression, anxiety and global functioning, the two clinical groups showed different temperamental, coping and social patterns. Specifically IA patients compared with the PG patients showed a greater mental and behavioural disengagement associated with an important interpersonal impairment. The two clinical groups shared an impulsive coping strategy and socio-emotional impairments. CONCLUSIONS: Despite IA and PG patients presenting similar clinical symptoms, IA condition was characterised by a more relevant mental, behavioural, and social disengagement compared to PG condition.

[To define internet addiction]. / Definire la dipendenza da internet.

Internet addiction is a new behavioral disorder difficult to define, especially when referring to young teenagers who make great use of web-mediated relationships. It's necessary to separate the cases of overt dependency on those in which the abuse of internet seems to have a different value, offering the only way to achieve the possible relationship. Internet is mediating a new way of communicating and thinking, this may favor the onset of clinical phenomena intended to surprise.

Internet addiction: hours spent online, behaviors and psychological symptoms.

OBJECTIVE: The aim of this study was to investigate psychopathological symptoms, behaviors and hours spent online in patients with internet addiction disorder (IAD) at a new psychiatric service for IAD inside a policlinic. METHOD: Eighty-six subjects participated in the study. Thirty-three patients asking for psychiatric consultation regarding their excessive use of the internet were assessed with IAD interview, internet addiction test (IAT), Symptom Checklist-90-Revised (SCL-90-R) and a brief sociodemographic survey. Moreover, patients had to respond to the following question: Over the last month, how much time have you spent online per week? At the end of psychiatric assessment, 21 of the 33 patients satisfied inclusion (IAD interview) and exclusion (psychotic disorders, neurocognitive deficits, dementia, serious mental delay, current alcohol or drug abuse) criteria. Twenty-one patients of the clinical group were compared with 65 subjects of a control group who were recruited online using IAT. RESULTS: IAD patients showed significantly higher scores on the IAT compared to subjects of the control group. Only item 7 (How often do you check your e-mail before something else that you need to do?) showed a significant inverse trend. SCL-90-R anxiety and depression subscale scores and item 19 (How often do you choose to spend more time online over going out with others?) of the IAT were positively correlated with number of weekly hours spent online in IAD patients. CONCLUSION: Findings suggest that a misuse of internet, characterized by many hours spent online avoiding interpersonal relationships with real and known people, could be an important criterion in the clinical interview in order to diagnose the IAD. The association between the lost interest in communicating with real people and psychological symptoms such as anxiety and depression could be relevant to detect IAD patients.

[Internet addiction and web-mediated psychopathology]. / Dipendenza da Internet e psicopatologia web-mediata.

The development of the Internet and its gradual mass distribution in the last 20 years have marked the beginning of a global revolution in the way of communicating and thinking. In this context, emerged disorders related to a pathological use of the network, up to forms of real addiction (Internet Addiction Disorder), similar to the use of psychotropic substances. The abuse of the Internet can seriously aggravate pre-existing psychopathological traits, which are the basis of addiction, resulting in a continuous process of disconnection from reality. The loss of interpersonal relationships, the change of mood, cognition completely oriented to the use of the network and disruption of temporal experience are common features in patients addicted to the Internet. There are also clear signs of intoxication and abstinence. Teenagers are particularly at risk, maybe because born in the "new virtual world" and therefore less aware of the risks that may ensue. At the Gemelli Hospital in Rome it's active an out-patient service for Internet Addiction Disorder with a treatment protocol that includes individual interviews, group rehabilitation and self-help groups for family members.

Chronic ketamine use increases serum levels of brain-derived neurotrophic factor.

RATIONALE: Ketamine is a non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids (EAAs) including glutamate and aspartate. The use of ketamine at subanaesthetic doses has increased because of its psychotomimetic properties. However, long-term ketamine abuse may interfere with memory processes and inhibit the induction of long-term potentiation (LTP) in the hippocampus, an effect probably mediated by its NMDA antagonist action. Neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as survival factors for selected populations of central nervous system neurons, including cholinergic and dopaminergic neurons. In addition, neurotrophins, particularly BDNF, may regulate LTP in the hippocampus and influence synaptic plasticity. OBJECTIVES: The purpose of this study was to test the hypothesis that ketamine use in humans is associated with altered serum levels of neurotrophins. METHODS: We measured by enzyme-linked immunosorbent assay the NGF and BDNF serum levels in two groups of subjects: frequent ketamine users and healthy subjects. RESULTS: Our data show that BDNF serum levels were increased in chronic ketamine users as compared to healthy subjects, while NGF levels were not affected by ketamine use. CONCLUSION: These findings suggest that chronic ketamine intake is associated with increases in BDNF serum levels in humans. Other studies are needed to explore the pharmacological and molecular mechanism by which ketamine, and/or other NMDA antagonists, may induce modification in the production and utilization of BDNF and alter normal brain function.

Acetyl-L-carnitine in the management of pain during methadone withdrawal syndrome.

INTRODUCTION: This study was designed to determine the short-term effect of acetyl-l-carnitine (ALC) on symptoms of withdrawal in opiate-dependent subjects and animals and, in particular, on pain, given the efficacy of ALC in other typologies of pain. The study consists of 2 branches: a clinical study and a preclinical one, both with a randomized placebo-controlled design. METHODS: Thirty subjects meeting clinical criteria for methadone dependence were consecutively recruited and treated with ALC 2 g/d or placebo for a 3-week detoxification period. Withdrawal symptoms and pain were evaluated through the Short Opiate Withdrawal Syndrome scale, and the Huskisson's analogue scale for pain. In the preclinical study, mice previously received a pretreatment (saline solution or morphine), and subsequently, each group was randomly divided in 4 subgroups that received a treatment of saline, methadone, ALC, or amitriptyline, respectively. Hot plate test and Writhing test were used to evaluate pain intensity. RESULTS: Average Short Opiate Withdrawal Syndrome total scores during the first 5 days of treatment resulted significantly higher in controls than in the ALC group (P < 0.05). Pain scores in the Huskisson's analogue scale were considerably lower in the group of patients taking ALC than in the control group after 1 week of ALC treatment until the end of the study. Results of the preclinical study show that the administration of methadone for 7 days in morphine-tolerant mice did not produce any modification of the pain threshold. By contrast, the 7-day coadministration of methadone and ALC in morphine-tolerant mice induced an analgesic effect evaluated 3 hours after the last injection. DISCUSSION: Acetyl-L-carnitine acted as an effective antihyperalgesic agent for relieving opiate-withdrawal hyperalgesia in animals and displayed clinical efficacy on other withdrawal symptoms such as muscular tension, muscular cramps, and insomnia. Considering its tolerability, the excellent side effect profile, the absence of significant interactions, and the lack of abuse potential, ALC can be considered as a useful pharmacological adjunct in the treatment of opiate withdrawal.

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.

Cocaine addiction: from habits to stereotypical-repetitive behaviors and punding.

"Punding" is a stereotypical motor behavior characterized by an intense fascination with repetitive handling and examining of objects. Since its first description in amphetamine and cocaine addicts, data on punding has only derived from studies performed in patients with Parkinson's disease (PD). Punding is classifiable as the most severe form of Repetitive Reward-Seeking Behaviours (RRSB) syndromes. The aim of this study was to investigate the occurrence and phenomelogy of RRSB acutely induced by cocaine in order to determine the prevalence, severity and distinctive features discriminating "punders" from "non-punders". A consecutive sample of 50 cocaine addicts received a clinical psychiatric interview. RRSB diagnosis and severity were assessed using a modified version of a previous published questionnaire designed to identify punding in patients with PD. In the present series, 38% of the cocaine addicts met the proposed diagnostic criteria for a RRSB and 8% were considered punders. Subjects with vs. without RRSB did not differ in terms of sex ratio, age, education, occupation, predisposing habits, duration of cocaine use, hours of sleep, comorbid psychiatric disorders, and concomitant use of other drugs. These results and the observation that in the majority of cases RRSB started soon after first drug intake, strongly suggest that an underlying unknown predisposition led to the development of these behaviors. In conclusion, RRSB and punding is much more common than has been described previously and the resultant social disability is often overlooked.

Plasma magnesium level and psychomotor retardation in major depressed patients.

Numerous studies have been performed on magnesium (Mg) metabolism in patients with mood disorders but consistent results have not been obtained. To date, systematic clinical data about Mg levels in major depressed patients according to the psychopathological profile are not available. In the present study we have investigated the relationship between plasma Mg level severity of symptoms and specific psychopathological dimensions (anhedonia and retardation) in 53 mild-to-moderately depressed patients (M/F = 21/32; mean age 46.49 +/- 13.48). The psychopathological status was assessed using standard psychometric evaluation scales: HAM-D for severity of depression, HAM-A for severity of anxiety symptoms, DRRS for psychomotor retardation and SHAPS for anhedonia. We did not find any significant correlation between total plasma Mg levels (0.86 +/- 0.09 mmol/L), severity of depression (HAM-D = 17.13 +/- 6.76) and anxiety (HAM-A = 16.62 +/- 6.60). A statistically significant correlation between Mg levels and psychomotor retardation was observed. Patients with higher psychomotor retardation scores (DRRS = 20.41 +/- 7.72) showed higher plasma Mg levels (0.89 +/- 0.07 mmol/L), even though they remained in the normal range, in comparison to patients with lower retardation scores (DRRS = 7.29 +/- 3.80; Mg = 0.82 +/- 0.10 mmol/L). A relationship between catecholamines and Mg metabolism has been described and our results support the hypothesis that hypermagnesaemia might lead to hypoactivity and psychomotor retardation which is so often observed in depressed patients.