Giovanni Martinotti

Prefrontal–thalamic–cerebellar gray matter networks and executive functioning in schizophrenia

OBJECTIVE Poor executive functioning is a core deficit in schizophrenia and has been linked to frontal lobe alterations. We aimed to identify (1) prefrontal cerebral areas in which decreased volume is linked to executive dysfunction in schizophrenia; and (2) areas throughout the brain that are volumetrically related to the prefrontal area identified in the first analysis, thus detecting more extended volumetric networks associated with executive functioning. METHOD Fifty-three outpatients with schizophrenia and 62 healthy controls, matched for age, gender and handedness, were recruited. High-resolution images were acquired on a 1.5 tesla scanner and regional gray and white matter volumes were analyzed by voxel-based morphometry within SPM5 (statistical parametric mapping, University College London, UK). Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). RESULTS Twenty-one patients with poor executive functioning showed reduced dorsolateral prefrontal and anterior cingulate gray matter volume as compared to 30 patients with high WCST performance, with a maximum effect in the left dorsolateral prefrontal cortex. Left dorsolateral prefrontal gray matter volume predicted WCST performance after controlling for possible confounding effects of global cognitive functioning, verbal attention span, negative symptoms, illness duration and education. In this area, both patient groups had less gray matter than healthy controls. Left dorsolateral prefrontal gray matter volume was positively related to dorsal prefrontal, anterior cingulate and parietal gray matter volume; and negatively related to thalamic, cerebellar, pontine and right parahippocampal gray matter volume. CONCLUSIONS Volumetric alterations in prefrontal-thalamic-cerebellar gray matter networks may lead to executive dysfunction in 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.

Mono- and polysubstance dependent subjects differ on social factors, childhood trauma, personality, suicidal behaviour, and comorbid Axis I diagnoses

BACKGROUND The study aimed to examine the clinical correlates of polysubstance dependence. SUBJECTS AND METHODS Seven hundred and fifty two substance-dependent subjects were interviewed with the Mini-International Neuropsychiatric Interview, the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA), and the Hamilton Depression Rating Scale (HDRS). Subjects completed the Childhood Trauma Questionnaire (CTQ), Eysenck Personality Questionnaire (EPQ), and Barratt Impulsivity Scale (BIS). Subjects found to have polysubstance dependence were compared with subjects with monosubstance dependence. RESULTS Polysubstance dependence was found in 48.3% of the subjects. Subjects with polysubstance dependence were significantly younger, more were separated/divorced and unemployed, and they had significantly higher CTQ scores for childhood emotional and physical neglect, higher EPQ psychoticism scores, higher BGLHA aggression scores, and higher BIS impulsivity scores. Significantly more of the polysubstance dependent subjects had attempted suicide, self-mutilated, and exhibited aggressive behavior. Significantly more monosubstance dependent subjects had an Axis I psychiatric disorder and they had higher HDRS depression scores. CONCLUSIONS Polysubstance dependence is common among the groups studied and may be associated with certain socio-demographic, developmental, and personality factors.

The language of schizophrenia: An analysis of micro and macrolinguistic abilities and their neuropsychological correlates

Language disturbance is one of the main diagnostic features in schizophrenia and abnormalities of brain language areas have been consistently found in schizophrenic patients. The main aim of this study was to describe the impairment of micro and macrolinguistic abilities in a group of twenty-nine schizophrenic patients during the phase of illness stability compared to forty-eight healthy participants matched for age, gender and educational level. Microlinguistic abilities refer to lexical and morpho-syntactic skills, whereas macrolinguistic abilities relate to pragmatic and discourse level processing. Secondary aims were to detect the effect of macrolinguistic on microlinguistic ability, and the neuropsychological impairment associated with the linguistic deficit. The linguistic assessment was performed on story-telling. Three narratives were elicited with the help of a single-picture stimulus and two cartoon stories with six pictures each. A modified version of the Mental Deterioration Battery was used to assess selective cognitive performances. A series of t-tests indicated that all the macrolinguistic variables were significantly impaired in schizophrenic patients in at least one of the three story-tellings. Furthermore, the limited impairment found in microlinguistic abilities was influenced by macrolinguistic performance. Multivariate stepwise regression analyses suggested that reduced attention performances and deficit in executive functions were predictors of linguistic impairment. Language production in schizophrenia is impaired mainly at the macrolinguistic level of processing. It is disordered and filled with irrelevant pieces of information and derailments. Such erratic discourse may be linked to the inability to use pragmatic rules and to cognitive deficits involving factors such as attention, action planning, ordering and sequencing.

Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics

Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high‐risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability.

Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. Naltrexone

Abstract Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5–15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90–Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.

Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study

Abstract The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy. Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively. Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores. In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.

Clinical features, response to treatment and functional outcome of bipolar disorder patients with and without co-occurring substance use disorder: 1-year follow-up

INTRODUCTION Bipolar disorder patients (BP) with comorbid Substance Use Disorder (SUD) may present clinical features that could compromise adherence and response to pharmacological treatment. The purpose of this study was to examine clinical and psychopathological features of BP with and without comorbid SUD in a real-world setting. METHODS The sample was composed by 131 affective patients. Sixty-five patients were affected by Bipolar Disorder I (BP-I, 49.2%), 29 by Bipolar Disorder II (BP-II, 22.3%) and 37 by Cyclothymic Disorder (CtD, 28.5%), according to DSM-IV. Sixty-six patients were diagnosed for a comorbid SUD. All patients have been submitted to psychometric assessment with Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Young Mania Rating Scale (YMRS), Global Assessment Scale (GAS), Social Adjustment Self-reported Scale (SASS), Quality of Life Scale (QoL), at baseline and repeated follow-up periods (1, 3, 6, 12 months). RESULTS BP comorbid for SUD were more likely diagnosed as BP-II and CtD and were less likely to present a moderate-severe manic symptomatology. Furthermore, personality disorders were more frequent in SUD patients than in non-comorbid BP. BP with SUD were not different for primary outcome measure (HDRS, HARS, YMRS, GAS) from non-comorbid BP; however, BP with SUD were significantly more impaired in social functioning (SASS) at any stage of the follow-up and poor functioning increased the risk of relapse in substance use during treatment. Finally, SUD comorbidity did not represent a risk factor for treatment drop-out, while in our sample young age, low treatment dosage and BP-I diagnosis were significantly associated with drop-out. DISCUSSION The primary finding of this work is that BP with comorbid SUD are significantly more compromised in social functioning. Second, these patients were less likely to be diagnosed for BP-I and to present a severe manic symptomatology. Finally, we found that the diagnosis of SUD, but young age, low treatment dosage and BP-I diagnosis to be risk factors for treatment drop-out. Physicians should be alert to these differences in their clinical practice.

Psychometric characteristic of the Italian version of the Temperament and Character Inventory—Revised, personality, psychopathology, and attachment styles

In this article, we described the psychometric characteristics of the revised version of the Cloningers personality Temperament and Character Inventory (TCI-R), Italian translation. Two independent samples, which were composed of 355 and 385 nonclinical mother-language Italian subjects, respectively, completed the TCI-R. A further sample of psychiatric outpatients was compared with community samples. We analyzed the internal consistency of each dimension, the test-retest reliability and the factorial structure of the questionnaire. Furthermore, we explored the potential association between personality, psychopathologic indicators (evaluated by the Symptom Checklist-90), behavior dyscontrol measures, and adaptive and maladaptive interpersonal styles. As a whole, the internal consistency of the TCI-R scales was adequate, although some differences in Cronbach alpha values were observed between the 2 samples in some TCI-R subfacets. The factorial structure was consistent with the original hypothesis of Cloninger and test-retest showed a good stability of the scores over the time. Normal data for the Italian population were also calculated. Furthermore, the character dimensions of self-directedness and cooperativeness were related with some psychopathologic domains in our sample and negatively with impulsiveness, anger, and hostility. Novelty seeking was associated with impulsiveness, whereas harm avoidance was associated with anger and hostility. On the contrary, persistence and reward dependence were inversely correlated with such traits. Harm avoidance, reward dependence, self-directedness, and cooperativeness were strongly related with measures of attachment. Finally, significant differences were observed in both temperament and character traits between community subjects and psychiatric outpatients. In the present study, the validity of the Italian translation of the TCI-R is therefore supported. Personality features are also confirmed as risk factors for specific psychopathologic domains, impulsivity, anger, and hostility. Furthermore, we found attachment styles of nonclinical subjects correlated with personality features.

Alcohol protracted withdrawal syndrome: the role of anhedonia

Aims: The aim of the present study is to characterize the relevance of withdrawal symptoms during the first 12 months of abstinence and their relation to anhedonia and craving. Methods: 102 detoxified subjects meeting clinical criteria for Alcohol Dependence in Remission were recruited at various time since the detoxification and subdivided into four groups according to the length of abstinence (group 1: 15–30 days; group 2: 30–90 days; group 3: 90–180 days; group 4: 180–360). Withdrawal symptomatology was assessed through the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The Visual Analogue Scale (VAS) for craving, the Snaith–Hamilton Pleasure Scale (SHAPS) and the Subscale for Anhedonia in the Scale for the Assessment of Negative Symptoms (SANSanh) where the other instruments employed. Results: Both anhedonia and withdrawal symptoms were identified in all the groups considered. SHAPS score and VAS for craving showed a significant difference between group 1 and groups 2, 3, and 4. As to CIWA-Ar items, apart from “orientation/clouding of sensorium” that was higher in groups 3 and 4 with respect to both groups 1 and 2, withdrawal symptoms were not significantly different between the periods considered. SHAPS and SANSanh were positively correlated to CIWA-Ar total score, “nausea and vomiting,” and “headache/fullness in head.” Discussion: The results of this study suggest the relevance of protracted withdrawal well beyond the limited period following the abrupt cessation of alcohol intake. The clinical dimension of anhedonia cannot be separated from the other behavioral symptoms of withdrawal and should be considered as part of the same process.