Riccardo Augusto Paoli

Neuropsychology, social cognition and global functioning among bipolar, schizophrenic patients and healthy controls: Preliminary data

This study aimed to determine the extent of impairment in social and non-social cognitive domains in an ecological context comparing bipolar (BD), schizophrenic (SKZ) patients and healthy controls (HC). The sample was enrolled at the Department of Psychiatry of Policlinico Hospital, University of Milan; it includes stabilized SKZ patients (n = 30), euthymic bipolar patients (n = 18) and HC (n = 18). Patients and controls completed psychiatric assessment rating scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB) that contains both ecological tests of executive function and social cognition, in order to better detect cognitive deficits in patients with normal results in standard executive batteries. The three groups differed significantly for gender and substance abuse, however, the differences did not influence the results. BD patients showed less impairment on cognitive performance compared to SKZ patients, even in “ecological” tests that mimic real life scenarios. In particular, BD performed better than SKZ in verbal memory (p < 0.0038) and BACS symbol coding (p < 0.0043). Regarding the ESCB tests, in the Hotel task SKZ patients completed significantly less tasks (p < 0.001), showed a greater number of errors in Multiple Errands Test (MET-HV) (p < 0.0248) and a worse performance in Theory of Mind (ToM) tests (p < 0.001 for the Eyes test and Faux pas test). Both patients groups performed significantly worse than HC. Finally, significant differences were found between the two groups in GAF scores, being greater among BD subjects (p < 0.001). GAF was correlated with BACS and ESCB scores showing the crucial role of cognitive and ecological performances in patients global functioning.

An epidemiologic and clinical overview of medical and psychopathological comorbidities in major psychoses

The presence of comorbidity in major psychoses (e.g., schizophrenia and psychotic subtypes of bipolar disorder and major depressive disorder) seems to be the rule rather than the exception in both DSM-IV and ICD-10. Examining comorbidity in major psychoses, however, requires an investigation into the different levels of comorbidity (either full-blown and subsyndromal) which should be analyzed in both psychopathological and medical fields. On one hand, the high prevalence of psychiatric comorbidity in major psychoses may be the result of the current nosographic systems. On the other hand, it may stem from a common neurobiological substrate. In fact, comorbid psychopathological conditions may share a biological vulnerability, given that dysfunction in specific brain areas may be responsible for different symptoms and syndromes. The high rates of comorbidity in major psychoses require targeted pharmacological treatments in order to effectively act on both the primary diagnosis and comorbid conditions. Nevertheless, few controlled trials in comorbid major psychoses had been carried out and treatment recommendations in this field have mostly an empirical basis. The aim of the present article is to provide a comprehensive and updated overview in relation to epidemiological and clinical issues of comorbidity in major psychoses.

New approaches to the pharmacological management of generalized anxiety disorder

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and serotonine reuptake Inhibitors (SNRIs) together with pregabalin are actually considered by international guidelines as the first-line choice for generalized anxiety disorder (GAD) treatment. However, 50% of GAD patients have poor response to first-line treatments and different molecules, such as atypical antipsychotics and mood stabilizers, have been used for treating this condition. Purpose of the present article is to provide an overview of the most recent pharmacological approaches for the treatment of GAD and the rationale for their use. Areas covered: A research in the main database sources has been conducted to obtain an overview of the new pharmacological approaches in GAD (anticonvulsants, atypical antipsychotics, agomelatine, memantine, ondansetron and riluzole). Expert opinion: Among unlabelled molecules, quetiapine seems to have the most robust evidence of efficacy in GAD. Valproic acid and agomelatine appear to be effective in GAD patients, but the data are preliminary and need to be confirmed by future studies. Quetiapine is a promising molecule for GAD treatment but its use would be complicated by long-term metabolic side effects. Future research will have the objective to find more targeted molecules for the treatment of this disorder in light of its specific etiology.

White matter metabolism differentiates schizophrenia and bipolar disorder: a preliminary PET study

Fluorodeoxyglucose-F18 positron emission tomography studies (FDG-PET) have shown similar corticolimbic metabolic dysregulation in bipolar disorder and schizophrenia, with hypoactive prefrontal cortex coupled with hyperactive anterior limbic areas. However, it is not clear whether white matter metabolism connecting these regions is differently affected in the two disorders. Twenty-six patients with schizophrenia (mean age ± S.D.=30.23 ± 9.7 year-old; 19 males; mean weight ± S.D.=71 ± 3 kg) and 26 patients with bipolar disorder (mean age ± S.D.=48.73 ± 13 year-old; 18 males; mean weight ± S.D.=75 ± 15 kg) underwent an FDG-PET scan. Normalized datasets the two groups of patients were compared on a voxel-by-voxel basis using a two-sample t statistic test as implemented in SPM8, and adding age as covariate. Group differences were assessed applying a threshold of p<0.0005. White matter metabolic rates significantly differed between schizophrenia and bipolar disorder, whereas no differences were shown for cortical activity. This is the first FDG-PET, to our best knowledge, directly comparing subjects with schizophrenia to those with bipolar disorder. It reports decreased activity in the center of large fronto-temporal and cerebellar white matter tracts in patients with schizophrenia in respect to those with bipolar disorder. This feature may characterize and differentiate the regional brain metabolism of the two illnesses.

The relationship between binge eating disorder and non-purging bulimia nervosa

Aims.To further investigate the differentiation between non-purging bulimia nervosa (BN-NP) and binge eating disorder (BED), particularly as concerns weight-shape overconcern affecting self-esteem, a core belief to both anorexia and bulimia nervosa. Methods.Twenty-five female subjects with BN-NP and 25 female subjects with BED, consecutively referred to the Eating Disorder Unit of the DPPhNB, were administered the BEDCI, the EDI-2 and the BUT. Results.BED patients had a higher BMI (35.5 vs. 23.8 kg/m2, p<0.0001 and were slightly older than BN-NP ones. Weight-shape concerns as one of the main/the most important things influencing self-esteem were reported by 68% of BN-NP patients and 62.5% of BED ones. Age at onset of binge-eating, weight-cycling, overall impairment due to the eating behavior, sexual harassment, depressive and substance abuse comorbidity were equally represented in the two groups of patients. BN-NP patients scored higher than BED ones as regards EDI drive for thinness (p<0.05) and BUT weight phobia (p<0.05), with these scores significantly related to differences in BMI (p<0.0005 and p=0.012). Weight-shape overconcern influencing self-esteem was predictive of an earlier onset of binge-eating (p<0.05) and higher scores at the BUT weight phobia, and body image concerns (p<0.05). Conclusions.Differences between BED and BN-NP seem to be more of degree than type and there seems little value in the separation between BED and BN-NP based on weight-shape concerns that substantially impair self-esteem. This construct seems core to both disorders and plays a substantial role in triggering and maintaining the binge-eating cycle.

Correlation between neuropsychological and social cognition measures and symptom dimensions in schizophrenic patients

Neurocognitive and social cognition deficits have been largely reported in Schizophrenia (SKZ) but their association with psychopathology remains uncertain. Our purpose was to explore the relationship between symptom dimensions and neuropsychological performances. We enrolled 35 stabilized schizophrenic outpatients of the Department of Psychiatry of Policlinico Hospital, University of Milan, who completed psychiatric Rating Scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB). Disorganized dimension seems to have the most significant impact on cognition, being associated with performance in several BACS subtests (verbal memory, working memory, motor speed, symbol coding, Tower of London) and ESCB tasks (MET and Hotel task number of tasks attempted, number of broken MET rules, sum of deviations in Hotel Task). Positive dimension correlated with performance in verbal fluency, negative dimension with IOWA Test results, cognitive dimension with MET number of inefficiencies and Eyes test score. Impulsive-aggressive and depressive dimensions weakly correlated only with Faux Pas test. Our study supports the existence of a specific disorganized dimension in SKZ, separated from cognitive dimension evaluated through clinical instruments (e.g. PANSS), but capable of influencing cognitive abilities. Furthermore, it strengthens the validity of ecological tasks in evaluating cognition in SKZ.

Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study

BACKGROUNDnBipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET).nnnMETHODSnTwenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired.nnnRESULTSnGray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients.nnnCONCLUSIONSnThese findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Gray matter volumes may predict the clinical response to paliperidone palmitate long-acting in acute psychosis: A pilot longitudinal neuroimaging study

In schizophrenia, paliperidone palmitate (PP) long acting injectable (LAI) has been reported to sustain plasma concentrations and improve clinical symptoms. Moreover, it has also been demonstrated the important role of total gray matter (GM) volumes in predicting the clinical outcome. However, no studies investigating the association between PP-LAI treatment and brain morphometry has been published so far. Therefore, the main aim of our 24 weeks prospective observational exploratory study was to investigate the relation between brain anatomy and clinical outcome in seven patients with acute psychosis treated with PP-LAI. At baseline and every month (from T0 to T6) patients were clinically evaluated with the Brief Psychiatric Rating Scale (BPRS). 3T Magnetic Resonance Imaging at baseline was acquired and total GM and intracranial volumes were extracted to explore their predictive values on BPRS scores. After 24 weeks of treatment with PP-LAI, patients showed statistically significant improvements in BPRS scores. Moreover, subjects with higher total GM volumes had a significantly higher BPRS improvement at 24 weeks compared to patients with lower total GM volumes. Our findings confirm the effectiveness of PP-LAI in treating acute psychosis and suggest that greater GM volumes predict drug response, potentially supporting a favorable prognosis.

The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study

BACKGROUNDnSomatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive.nnnOBJECTIVEnThis study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures.nnnMETHODnWe used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits.nnnRESULTSnCompared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected).nnnCONCLUSIONnOur results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants

Background: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. Methods: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. Results: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). Conclusion: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings.