Massimo Di Giannantonio

The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Anhedonia and substance dependence: clinical correlates and treatment options

Anhedonia is a condition in which the capacity of experiencing pleasure is totally or partially lost, and it refers to both a state symptom in various psychiatric disorders and a personality trait. It has a putative neural substrate, originating in the dopaminergic mesolimbic and mesocortical reward circuit. Anhedonia frequently occurs in mood disorders, as a negative symptom in schizophrenia, and in substance use disorders. In particular, we focus our attention on the relationships occurring between anhedonia and substance use disorders, as highlighted by many studies. Several authors suggested that anhedonia is an important factor involved in relapse as well as in the transition from recreational use to excessive drug intake. In particular, anhedonia has been found to be a frequent feature in alcoholics and addicted patients during acute and chronic withdrawal as well as in cocaine, stimulant, and cannabis abusers. Furthermore, in subjects with a substance dependence disorder, there is a significant correlation between anhedonia, craving, intensity of withdrawal symptoms, and psychosocial and personality characteristics. Therefore treating anhedonia in detoxified alcohol-dependent subjects could be critical in terms of relapse prevention strategies, given its strong relationship with craving.

Association of polymorphism (Val66Met) of brain-derived neurotrophic factor with suicide attempts in depressed patients

Introduction: Recent post-mortem studies of suicide victims have implicated brain-derived neurotrophic factor (BDNF) in suicide. Therefore, it was decided to examine the possible role of a gene in the regulation of BDNF activity in relation to suicidal behaviour among depressed patients. Method: A series of 170 depressed patients were evaluated for their history of suicide attempts and genotyped for the BDNF Val66Met polymorphism (SNP ID: rs6265). Depressed patients who had (n = 97) or had not (n = 73) attempted suicide were compared. Results: Depressed patients who carried the BDNF Val66Met polymorphism variant (GA + AA) appeared to show a significantly increased risk of suicidal behaviour. The risk of a suicide attempt was also significantly higher among those reporting higher levels of childhood emotional, physical and sexual abuse. Secondary analyses suggested that depression severity was a significant risk factor only in the wild-type BDNF genotype, and that the risk of suicide attempts was more predictable within the wild-type group. Conclusion: These preliminary data suggest that BDNF may play a role in the suicidal behaviour of depressed patients.

Aggression, Impulsivity, Personality Traits, and Childhood Trauma of Prisoners with Substance Abuse and Addiction

Introduction: The aim of our study is then to analyze psychological and judicial features of a subgroup of inmates with substance abuse. Methods: Prisoners with substance abuse (n = 312) were compared to prisoners without substance abuse (n = 591). Recruited inmates completed a semistructured interview for collection of sociodemographic and judicial data and a battery of psychometric tests for assessement of aggression, impulsivity, depression, personality traits, hostility, resilience, and childhood trauma. Results: Substance abusers had on average multiple incarcerations (78.8%), more juvenile convictions (60.2%), more violent behaviors during detention (29.8%), and a history of one or more suicide attempts (20.8%). They also had higher scores on subscales for childhood trauma, higher scores for psychoticism and neuroticism, higher impulsivity levels, worse resilience, increased hostility, and prevalent suicidal ideation. Conclusion: Prisoners with substance abuse constitute a subgroup with increased judiciary and psychiatric issues, possibly due to early life history and psychological characteristics, such as high impulsivity and aggressiveness, poor resilience, and higher suicidal risk.

Substance abuse and suicide risk among adolescents

The aim of this paper was to review the literature concerning the relationship between suicide and substance abuse behaviours among adolescents, focusing on epidemiology, comorbidity and preventive programmes. We performed a Pubmed/Medline, Scopus, PsycLit and PsycInfo search to identify all papers and book chapters during the period between 1980 and 2011. Adolescents with substance abuse disorder who attempt or complete suicide can be characterized as having mood disorders, stressful life events, interpersonal problems, poor social support, lonely lives and feelings of hopelessness. The research supports the existence of a strong relationship between suicide and substance abuse. Preventive programmes should be based on the detection of risk factors associated with both suicide and substance abuse disorder. Management programmes should combine different therapeutic strategies such as peer-to-peer education, school-based programmes, psychotherapy and pharmacological treatment. Evidence suggests that targeted suicide prevention programmes can be delivered which reduce the burden associated with substance abuse and suicide in youths.

The Emerging Role of Melatonin Agonists in the Treatment of Major Depression: Focus on Agomelatine

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual subtreshold symptoms. This compound showed a relative early onset of action as well as an excellent safety and tolerability profile linked to a low discontinuation rate in MDD patients. Moreover, some data suggest that agomelatine has not only antidepressant effects but also anxiolytic effects, with a potential benefit both on anxiety symptoms associated with MDD and in the treatment of generalised anxiety disorder. This review will summarise the role of the melatonergic system in MDD and will describe the characteristics of agomelatine, focusing on its efficacy and safety in the treatment of MDD.

Risk Factors for Attempting Suicide in Prisoners

We wished to examine determinants of suicidal behavior in prisoners. 903 male prisoners had a psychiatric interview which included various psychometric tests. Suicide attempters were compared with prisoners who had never attempted suicide. Significantly more of the attempters had a history of psychiatric disorder, substance abuse, a family history of suicidal behavior, convictions for violent crime, had exhibited aggressive behavior in jail, and had higher BGLHA aggression scores. A similar pattern of risk factors was found for prisoners with suicidal ideation. A lifetime history of attempting suicide, or of having suicidal ideation, is frequent in prisoners. Risk factors include family, developmental, aggression, personality, psychiatric, and substance abuse factors.

BDNF serum levels in subjects developing or not post-traumatic stress disorder after trauma exposure

Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome. To elucidate these issues, in this study we analyzed BDNF serum levels in two groups of subjects: patients with trauma exposure who developed PTSD, and subjects with trauma exposure who did not develop PTSD. We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects. Thus, these data suggest that BDNF might be involved in pathophysiology of PTSD and consequently therapeutic approaches aimed at restoring BDNF serum levels may be beneficial to this pathology.

Novel Psychoactive Substances in Young Adults with and without Psychiatric Comorbidities

Objective. Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. Methods. A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. Results. Alcohol consumption was more frequent in the healthy young population compared to age-matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003). Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001). Conclusions. The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary.

The melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice.

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in “real world” clinical practice will be also discussed.