Salivary α-Synuclein as a Candidate Biomarker of Parkinsonism in 22q11.2 Deletion Syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early-onset Parkinson's disease. However, the pathophysiological mechanisms underlying parkinsonism remain poorly understood. OBJECTIVE: The objective is to investigate salivary total α-synuclein levels in 22q11.2DS patients with and without parkinsonian motor signs. METHODS: This cross-sectional study included 10 patients with 22q11.2DS with parkinsonism (Park+), ten 22q11.2DS patients without parkinsonism (Park-), and 10 age and sex-comparable healthy subjects (HS). Salivary and serum α-synuclein levels were measured using enzyme-linked immunosorbent assay. RESULTS: Salivary total α-synuclein concentration was significantly lower in Park (+) patients than in Park (-) patients and HS (P = 0.007). In addition, salivary α-synuclein showed good accuracy in discriminating Park (+) from Park (-) patients (area under the curve = 0.86) and correlated with motor severity and cognitive impairment. CONCLUSION: This exploratory study suggests that the parkinsonian phenotype of 22q11.2DS is associated with a reduced concentration of monomeric α-synuclein in biological fluids.

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.

A Revision on the Effectiveness of Omega-3 Polyunsaturated Fatty Acids as Monotherapy in the Treatment of Major Depressive Disorder.

Background: Insufficient effectiveness and a difficult tolerability profile of antidepressant drugs for the treatment of major depressive disorder (MDD) have been reported, and polyunsaturated fatty acids (PUFAs) have been posited as reliable therapeutic alternatives. The present study investigated the efficacy of omega-3 PUFAs as monotherapy for MDD. Methods: Two well-trained reviewers independently looked at the most significant randomized clinical trials (RCTs) from the PubMed database regarding PUFAs' employment in MDD compared to placebo; "major depressive disorder" and "omega-3 fatty acids," or "omega-6 fatty acids," or "polyunsaturated fatty acids (PUFA)," or "n - 3 polyunsaturated fatty acids," or "eicosapentaenoic acid (EPA)," or "docosahexaenoic acid (DHA)" were used as the medical subject keywords. Results: Of the initial 96 potential RCTs based on titles and abstracts, 82 studies did not meet the inclusion criteria and were excluded. Six studies were excluded from the remaining 14 after full text revision. Eight RCTs met all the inclusion/exclusion criteria without reporting clear evidence of PUFAs' effectiveness in the treatment of MDD. Conclusion: At present, there is no opportunity to recommend the use of omega-3 PUFAs monotherapy for the treatment of MDD, although their supplementation may be useful in some specific populations.

Structural Cerebellar Abnormalities and Parkinsonism in Patients with 22q11.2 Deletion Syndrome.

Background: The phenotypic expression of 22q11.2 deletion syndrome (22q11.2DS) is variable and may include cognitive, psychiatric, and neurological manifestations, e.g., parkinsonism. We investigated brain structural alterations in patients with 22q11.2DS with and without parkinsonism (Park+ and Park-) in comparison with healthy controls (HCs). Methods: Voxel-based morphometry was performed on 3D T1-weighted MR images to explore gray matter volume (GMV) differences between 29 patients (15 Park+, 14 Park-), selected from a consecutive series of 56 adults diagnosed with 22q11.2DS, and 24 HCs. One-way ANOVA and multiple linear regression analyses were performed to explore group differences in GMV and correlations between clinical scores (MDS-UPDR-III and MoCA scores) and structural alterations. Results: Significant between-group differences in GMV were found in the cerebellum, specifically in bilateral lobes VIII and left Crus II, as well as in the left superior occipital gyrus. Although both Park+ and Park- patients showed GMV decrements in these regions with respect to HCs, GMV loss in the right lobe VIII and left Crus II was greater in Park+ than in Park- patients. GMV loss did not correlate with clinical scores. Conclusions: Patients with 22q11.2DS and parkinsonism manifest specific cerebellar volume alterations, supporting the hypothesis of neurodegenerative processes in specific cerebellar regions as a putative pathophysiological mechanism responsible for parkinsonism in patients with 22q11.2DS.

Problematic Use of the Internet Mediates the Association between Reduced Mentalization and Suicidal Ideation: A Cross-Sectional Study in Young Adults.

Suicide is a major public health problem, and it is urgent to investigate its underlying clinical and psychological concomitants. It has been suggested that low mentalization skills and problematic use of the internet (PUI) are factors that can play a role in suicidal behaviors. It is possible that poor mentalization skills contribute to leading to forms of PUI, which, in turn, can represent triggers for suicidal ideation (SI). We tested this hypothesis through a quantitative and cross-sectional study on a sample (n = 623) of young adults (age range: 18−34). Self-report measures investigating symptoms related to Social Media Addiction (SMA), Internet Gaming Disorder (IGD), mentalization capacity, and SI were used. A single mediation analysis with two mediators was carried out to evaluate the direct and indirect effects of mentalization on SI through the mediating role of SMA- and IGD-related symptoms, controlling for potential confounding factors (e.g., socio-demographic and addiction-related variables). The four explored variables were significantly associated with each other (all p < 0.001) across all subjects; the mediational model showed that the total effect of mentalization on SI was significant (B = −0.821, SE = 0.092 (95% CI: −1.001; −0.641)) and that both SMA- (B = −0.073, SE = 0.034 (95% CI: −0.145; −0.008)) and IGD-related symptoms (B = 0.046, SE = 0.027 (95% CI: −0.107; −0.001)) were significant mediators of such association. Our findings support the possibility that PUI severity plays a relevant role in mediating the association between low mentalization skills and levels of SI.

Gender modulation of psychopathological dimensions associated to suicidality.

OBJECTIVES: The dimensional approach to psychopathology has been proposed to reliably evaluate suicidality. Potential gender modulation of psychopathological dimensions associated to suicide attempts was investigated. METHODS: 91 subjects who committed a near-lethal suicide (SA group) and 374 who did not (nSA group) were recruited in a Psychiatric Intensive Care Unit regardless of their categorical diagnosis. The Hamilton Depression Rating Scale (HAM-D), the Brief Psychiatric Rating Scale - Expanded version (BPRS-E) and the Scale for Rapid Dimensional Evaluation (SVARAD) were administered at the admission. A Factorial Multivariate ANOVA was conducted according to General Linear Model: Sex and Suicidality were input as fixed factors, HAM-D, BPRS-E and SVARAD scores as dependent variables. RESULTS: Men with SA (MSA) displayed significant lower scores in SVARAD Activation dimension compared to women with SA (FSA) (p=0.049), men without SA (MnSA) (p<0.001) and women without SA (FnSA) (p<0.001). Both SA groups displayed significant higher scores compared to nSA groups in regard of Depression item (BPRS-E) (p<0,001). The MSA group displayed significant lower scores in Psychomotor agitation (HAM-D) compared to FSA (p=0,044), MnSA (p<0,001) and FnSA (p<0,001). CONCLUSIONS: By means of multifactorial statistics sex resulted a moderator of the relation between activation/agitation and suicidality, despite categorical diagnosis.

Sexual Habits and Sexual Dysfunctions in a Sample of Patients with Psychotic Disorders Compared to a Group of Healthy Adults.

BACKGROUND: There is a growing body of literature on the association between psychosis and sexual dysfunction. However, most studies have focused on sexual dysfunction and have not investigated the sexual lives of patients with psychosis across a broader range. MATERIAL AND METHODS: Consecutive patients with a diagnosis of acute psychosis or schizophrenia were recruited to the study after obtaining informed consent (n = 46). In addition, healthy control subjects were recruited (n = 52). Sociodemographic and clinical data, psychopathology, and sexual functioning were assessed. Independent sample t-test to determine group differences was obtained. RESULTS: In both the male and female groups, there are significant differences between psychotic individuals and healthy controls in several areas of their sexual functioning: the control group seemed to better perceive Couple sexuality, Self-eroticism, and overall appeared to have a higher Quality of sexual life; on the other hand, the group of patients with psychosis displayed higher scores in Sexual dysfunction. CONCLUSIONS: A poor sexual quality of life may be found in patients with psychotic disorders. Assessment of sexual function in these patients is necessary to identify and manage issues and provide support and help to patients in this important area of life.

Prevalence and incidence of psychotic disorders in 22q11.2 deletion syndrome: a meta-analysis.

22q11.2 deletion syndrome (22q.11.2DS) might be one of the strongest genetic risk factors for psychosis, but robust estimates of prevalence and incidence of psychotic disorders in this condition are not available. To address this gap, we performed a multistep systematic PRISMA/MOOSE-compliant literature search of articles reporting prevalence (primary outcome) or incidence (secondary outcome) of psychotic disorders in 22q11.2DS samples (protocol: https://osf.io/w6hpg) using random-effects meta-analysis, subgroup analyses and meta-regressions. The pooled prevalence of psychotic disorders was 11.50% (95%CI:9.40-14.00%), largely schizophrenia (9.70%, 95%CI:6.50-14.20). Prevalence was significantly higher in samples with a mean age over 18 years, with both psychiatric and non-psychiatric comorbidities and recruited from healthcare services (compared to the community). Mean age was also significantly positively associated with prevalence in meta-regressions (p < 0.01). The pooled incidence of psychotic disorders was 10.60% (95%CI:6.60%-16.70%) at a mean follow-up time of 59.27 ± 40.55 months; meta-regressions were not significant. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prevalence and incidence of psychotic disorders in 22q11.2DS individuals. It demonstrates that around one in ten individuals with 22q11.2DS displays comorbid psychotic disorders, and around one in ten will develop psychosis in the following five years, indicating that preventive approaches should be implemented systematically in 22q11.2DS.

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.

[Contemporary narcissism and paranoid developments]. / Narcisismo contemporaneo e sviluppi paranoidei.

Starting from a psychopathological approach, the current paper sought to describe psychological and relational consequences that in last decades derived from new valorization and productive processes on the basis of substantial socio-cultural transformations. This reasoning arises from the analysis of contemporary society in regard to which the ideology of performance has assumed a prominent role. The society of performance is subservient to the imperatives of profit and valorization which have been internalized by common sense deeply influencing identity related processes. In such a society, specific forms of mental sufferance regarding the experiences of failure, unworthiness and guilt may show up, being related to the potential failure of performances. These transformations show a significant effect on narcissistic dynamics which nowadays seem derived from a more fragile self-ideality. Narcissistic wounds, with their experiences of failure and worthlessness, are not the only psychopathological developments that may occur in this frame. What we sought to describe in the current paper is the possibility of different paranoid experiences arising from intrapsychic tensions in their turn related to the abovementioned socio-cultural transformations. The aim of this contribution was to describe specific transient paranoid developments that never appear structured as true delusions: these psychotic experiences may act as a rebalancing process, somehow compensatory, in regard to such psychological functions that have been stressed by identitary anguish and experiences of failure and worthlessness.

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.

Attentional functioning in individuals with 22q11 deletion syndrome: insight from ERPs.

The 22q11 deletion syndrome (22q11DS), or DiGeorge syndrome (DG), is one of the most common genetic deletion syndromes. DG also carries a high risk for psychiatric disorders, with learning disabilities frequently being reported. Impairments in specific cognitive domains, such as executive functioning and attention, have also been described. The aim of this study was to investigate attentional functioning in a group of subjects with DG using ERPs, and in particular the P300 and CNV components. We studied ten patients with DG and ten healthy subjects that performed a P300 Novelty task and a CNV motor task. P3b amplitude was significantly lower in patients than in controls, while P3b latency was comparable in patients and controls. The P3a parameters were similar in both groups. All CNV amplitudes were significantly lower in DG patients than in controls. DG patients displayed slower reaction times in the CNV motor task than healthy subjects. These results point to a cognitive dysfunction related above all to executive attentional processing in DG patients. In particular, a specific difficulty emerged in selective attention and in the ability to orient and to sustain the anticipatory attention required for an executive motor response.