Social cognition and real-life functioning in patient samples with 22q11.2 deletion syndrome with or without psychosis, compared to a large sample of patients with schizophrenia only and healthy controls.

Patients with the 22q11.2 deletion syndrome (DS) show an increased risk of developing a psychotic illness lifetime. 22q11.2DS may represent a reliable model for studying the neurobiological underpinnings of schizophrenia. The study of social inference abilities in a genetic condition at high risk for psychosis, like 22q11.2DS, may shed light on the relationships between neurocognitive processes and patients' daily general functioning. The study sample consisted of 1736 participants, divided into four groups: 22q11.2DS patients with diagnosis of psychotic disorder (DEL SCZ, N = 20); 22q11.2DS subjects with no diagnosis of psychosis (DEL, N = 43); patients diagnosed with schizophrenia without 22q11.2DS (SCZ, N = 893); and healthy controls (HC, N = 780). Social cognition was assessed through The Awareness of Social Inference Test (TASIT) and general functioning through the Specific Levels of Functioning (SLoF) scale. We analysed data through regression analysis. The SCZ and DEL groups had similar levels of global functioning; they both had significantly lower SLoF Total scores than HC (p < .001); the DEL SCZ group showed significantly lower scores compared to the other groups (SCZ, p = .004; DEL, p = .003; HC, p < .001). A significant deficit in social cognition was observed in the three clinical groups. In the DEL SCZ and SCZ groups, TASIT scores significantly predicted global functioning (p < .05). Our findings of social cognition deficit in psychosis-prone patients point to the possible future adoption of rehabilitation programmes, like Social Skills Training and Cognitive Remediation, during premorbid stages of psychosis.

Similar grey matter abnormalities in 22q11.2DS and chronic schizophrenia: a voxel-based morphometry study.

BACKGROUND: The 22q11.2 Deletion Syndrome (22q11.2DS) is considered the most reliable biological model to study genetic vulnerability to schizophrenia. It appears useful to investigate neuroanatomical characteristics of people with 22q11.2DS compared to chronic schizophrenia and healthy controls. METHODS: The sample consisted of 16 individuals with a diagnosis of schizophrenia for over 10 years (SCZ>10), 14 with a diagnosis for less than 10 years (SCZ≤10), 11 patients with 22q11.2DS with no diagnosis of psychotic disorder (DEL, n=11) and 19 healthy controls (HCs, n=19). Global intelligence (IQ) was evaluated for all subjects. Voxel-Based Morphometry (VBM) was employed to investigate potential differences between groups in grey matter volumes. RESULTS: VBM located the most significant difference between SCZ and HCs in the left medial frontal gyrus, where SCZ>10 group showed a significant reduction of grey matter volume; the same cluster resulted significantly decreased in DEL group compared to HCs as well. Despite the extensive grey matter abnormalities observed in 22q11.2DS, the DEL group showed the only significant differences compared to the SCZ>10 group in the right lingual gyrus volumes. CONCLUSIONS: Despite the small sample, our study identified a common area of grey matter loss both in idiopathic schizophrenia and 22q11.2DS.

Recognition of facial emotion expressions and perceptual processes in 22q11.2 deletion syndrome.

BACKGROUND: Social cognition (SC) deficits and of its facial emotion expression (FEE) component have been described in 22q11.2 Deletion Syndrome (22q11.2DS), a high-risk for schizophrenia (SCZ) systemic genetic syndrome. Correlations between deficits in FEE skills and visual-spatial abilities in people with 22q11.2DS warrant investigation. METHODS: The sample consisted of 37 patients with 22q11.2DS (DEL), 19 with 22q11.2DS and psychosis (DEL-SCZ), 23 with idiopathic SCZ, and 48 healthy controls. We assessed FEE through The Ekman 60 Faces test (EK-F60), visual-spatial skills with Raven's Standard Progressive Matrices, and symptom severity with the positive And negative syndrome scale. Statistics were conducted through multivariate analysis of variance and correlation analysis. RESULTS: Patients with 22q11.2DS performed worse that the other groups in recognizing Surprise, Disgust, Rage, Fear, and Neutral expressions on the EK-F60. Recognition of Surprise and Disgust correlated positively with visual-spatial abilities in patients with 22q11.2DS; negative and cognitive symptoms correlated negatively with recognition of Sadness, Surprise, and Disgust. CONCLUSIONS: Patients with 22q11.2DS show impairments of both peripheral and central steps of the emotional recognition process, leading to SC deficits. The latter are present regardless of the presence of a full-blown psychosis.

Clozapine-induced gastroesophageal rumination in 22q11.2 Deletion Syndrome. A case report on gastroesophageal side effects management without renouncing clozapine's effectiveness.

Despite entailing more severe and uncommon side effects in 22q11.2DS compared to idiopathic schizophrenia, we strongly believe that clozapine should continue to be considered the gold standard for all treatment-resistant schizophrenia, even in 22qDS.

Accuracy of self-assessment of real-life functioning in schizophrenia.

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n = 618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program.

Social cognition deficit and genetic vulnerability to schizophrenia in 22q11 deletion syndrome.

INTRODUCTION: 22q11.2 microdeletion syndrome (22q11DS) is associated with a 25% risk of psychotic onset. MATERIALS AND METHODS: The sample consist of 120 subjects: 39 schizophrenics (SCZ); 20 siblings of schizophrenic patients (SIB); 34 22q11DS non-psychotic patients (DEL); 17 22q11DS psychotic patients (DEL_scz); 30 control subjects (CS). Social cognition was evaluated with the awareness of social interference test. Intelligence Quotient (IQ) was calculated with Wechsler Adult Intelligence Scale. TASIT (Awareness of Social Inference Test) performance was analyzed via MANOVA, including IQ as covariate. RESULTS: Group and IQ showed significant effect (p < 0.001; p = 0.037). The only TASIT variables where IQ showed no effect were paradoxical sarcasm; sincerity; lie. In sincerity, CS group shows a better performance than both 22q11DS groups (p < 0.05). In paradoxical sarcasm and lie, CS group performed better than each clinical group (p < 0.05). Regarding lie, DEL group was worst also respect to SCZ group (p = 0.029). CONCLUSIONS: Our results show a specific social cognition deficit in 22q11DS and schizophrenia.

Myoclonic epilepsy, parkinsonism, schizophrenia and left-handedness as common neuropsychiatric features in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations. METHODS: We enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG). RESULTS: Thirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics. CONCLUSIONS: 22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients' genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p = .002), verbal IQ was decreased by 8.17 points (p = .0002) and performance IQ was decreased by 4.03 points (p = .028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.

Genetic and clinical features of social cognition in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2 DS) is widely known as one of the most compelling genetic models of schizophrenia so far, being almost 40% of the carriers affected by psychotic symptoms. Moreover, most of these subjects also show impairment in social cognition, which is a comprehensive array of function that guides social interaction with the others, leading as well to the acquisition of new cognitive and social skills. In the last decade researchers have argued whether social cognition dysfunctions could be underlined by specific genetic alterations, and whether these are linked to specific clinical features. Some valid candidate genes are RTN4R, that encodes a protein which inhibits axonal sprouting, DGCR8, crucial in mRNA processing, or catechol-O-methyltransferase (COMT) and proline oxydase 1 (PRODH), involved in catecholamine metabolism in frontal cortex. This is the first article to address the topic of social cognition in 22q11.2 DS from a wide perspective, with a highlight on its genetic characteristics. We will provide a narrative review of the most recent findings and we will point out new directions on this research path, in order to achieve an effective characterization of the neurobiological system underlying social behavior.

The complex relationship between self-reported 'personal recovery' and clinical recovery in schizophrenia.

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view. By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles.

Medial frontal gyrus alterations in schizophrenia: relationship with duration of illness and executive dysfunction.

Executive functioning is consistently impaired in schizophrenia, and it has been associated with reduced gray matter volume in prefrontal areas. Abnormalities in prefrontal brain regions have also been related to the illness duration. The aim of the study was to investigate the effect of executive functioning decline and chronicity in prefrontal regions of patients with schizophrenia. Participants comprised 33 schizophrenic patients, 18 with duration of illness (DoI) shorter than 10 years and 15 with duration of illness longer than 10 years. In addition, 24 healthy controls served as a comparison group. Participants performed the Wisconsin Card Sorting Test (WCST) and underwent structural magnetic resonance imaging. Patients with longer DoI showed significant reduction of gray matter volume in the left medial frontal gyrus compared with healthy controls. Moreover, there was a trend for greater gray matter volume decrease in patients with a longer illness duration compared with patients with shorter illness duration. There was no interaction between the volume of the left medial frontal gyrus performance on the WCST. The present study supports the hypothesis that medial frontal gyrus alterations in schizophrenia are sensitive to duration of illness. These alterations were not associated with executive functioning.

Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings.

BACKGROUND: Schizotypy, or the set of personality traits related to schizophrenia, is considered an endophenotypic manifestation that is more represented in first-degree relatives of patients with schizophrenia than in the general population. The assessment of schizotypy is primarily based on self-reports, and for this reason it presents several limitations. In order to assess schizotypy, this study proposes a diagnostic instrument based on clinical reports. METHODS: A sample of 66 subjects, composed of 25 outpatients with schizophrenia, 18 siblings of these patients and 23 healthy controls, was subjected to the personality assessment test SWAP-200 by trained clinical interviewers. To test the hypothesis of the difference between the profiles of the Personality Disorders within the schizophrenia spectrum, a Multivariate Analysis of Variance and subsequent planned comparisons were conducted. RESULTS: Patients with schizophrenia scored higher than both their siblings and the controls on all SWAP-200 scales; their siblings, compared to the healthy controls, showed significant statistical differences, with higher mean scores for paranoid (F(1,63) = 7.02; p = 0.01), schizoid (F(1,63) = 6.56; p = 0.013) and schizotypal (F(1,63) = 6.47; p = 0.013) traits (PD T scores of Cluster A and Q-factor scores for the schizoid scale [F(1,63) = 6.47; p = 0.013]). CONCLUSIONS: Consistent with previous data, first-degree relatives of patients with schizophrenia scored higher on schizophrenia-related personality traits than a general population comparison sample. SWAP-200, as an alternative diagnostic instrument to self-report measures, is able to reveal the higher prevalence of schizotypal traits in siblings of patients with schizophrenia, suggesting its possible use as a complementary instrument for the assessment of schizophrenia.

[Psychopathological comorbidity and quality of life in a sample of psychiatric patients]. / Comorbilità psicopatologiche e qualità della vita in un campione di pazienti psichiatrici.

INTRODUCTION: Psychopathological comorbidity in psychiatric patients is a common issue of epidemiological studies. Still, co-diagnoses have been suspected of being an artefact of a defective nosography rather than a realistic representation of multiple disorders co-existing in the same patient. This research aims at studying multiple disorders related to Axis I and Axis II of the DSM-IV in patients suffering from multiple, acute, and recurring psychotic episodes. Further, we aim to explore correlations between multiplicity of disorders and quality of life. MATERIALS AND METHODS: The experimental sample includes 30 patients having principal diagnoses belonging to the Axis I, regarded as major psychoses, and the control sample includes 39 volunteers, without any present or previous psychotic disorder. As to measuring instruments, two questionnaires have been used: the MOS (Medical Outcomes Study Short Form Health Survey, by Stein et al.) and TALEIA-400A (Test for AxiaL Evaluation and Interview for clinical, personnel, and guidance Applications, by L. Boncori et al.). A multiple analysis of variance has been calculated to verify differences in number of disorders between experimental and control groups, and bivariate correlations to verify negative relationship between co-diagnoses and quality of life. RESULTS: The patients' group showed significantly more disorders than the control group (p = 0.0007); subgroups of patients different in number and quality of co-diagnosis also significantly differed as to overall profile elevation and as to cognitive efficiency; the correlation between co-diagnoses and quality of life is significant and negative (r = -0.62, p < 0.01). CONCLUSIONS: Our data fit to outcomes from other studies showing that comorbidities can be regarded as an index of disorder severity.