Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.

Organizational and Individual Interventions for Managing Work-Related Stress in Healthcare Professionals: A Systematic Review.

The workplace represents a relevant source of stress for workers, being a risk factor for many mental disorders and psychological difficulties, including burn-out syndrome. Healthcare workers and other help-professions are particularly susceptible to work-related stress. The present systematic review aims to (1) identify available interventions for managing workplace-related stress symptoms; (2) assess their efficacy; and (3) discuss the current limitations of available interventions. A systematic review has been conducted, searching on PubMed, APA PsycInfo, and Scopus databases. Eighteen papers have been identified, which included different interventions for the management of work-related stress in healthcare professionals. These approaches can be grouped as follows: (1) interventions focusing on the individual level using cognitive-behavioral therapy (CBT) approaches; (2) interventions focusing on the individual level using relaxation techniques; and (3) interventions focusing on the organizational level. As regards interventions targeting the individual level using CBT approaches, mindfulness-based interventions were effective in reducing levels of burn-out, stress, and anxiety and in improving quality of life. As regards intervention using relaxation techniques, including art therapy, Emotional Freedom Techniques (ECT) and brief resilience retreats had a positive effect on the levels of anxiety, stress, and burnout. As regards interventions at the organizational level, we found no evidence for supporting its effectiveness in reducing the levels of burnout. Furthermore, available studies are heterogeneous in terms of assessment tools, target populations, and type of interventions, which limits the generalizability of findings.

Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo.

MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.

A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan.

Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human- and neural-specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin-related protein gene) mutation. We showed that CRISPR/Cas9-mediated gene correction of FKRP restored glycosylation of α-dystroglycan in iPSC-derived cortical neurons, whereas targeted gene mutation of FKRP in wild-type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α-dystroglycan. Using human FKRP-iPSC-derived neural cells for hit validation, we demonstrated that compound 4-(4-bromophenyl)-6-ethylsulfanyl-2-oxo-3,4-dihydro-1H-pyridine-5-carbonitrile (4BPPNit) significantly augmented glycosylation of α-dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC-derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development.

A hypothesis on Cotard's syndrome as an evolution of obsessive-compulsive disorder.

Cotard's syndrome usually presents as combined symptoms occurring in a broad series of neurological, psychiatric, and medical disorders, being severe depression the most frequent. The syndrome is not classified as a distinct clinical entity in the nosological systems but appears solely as a clinical condition in case reports. Thus, the diagnosis of Cotard's syndrome mainly centres on the psychiatric interview and the ability of the clinician to recognise specific symptoms due to the absence of both clinical instruments and diagnostic criteria. Cotard's syndrome has never been described to date in patients with a history of obsessive-compulsive disorder (OCD). We report a case of a 49-year-old woman presenting obsessive symptoms and related compulsions for more than 30 years. Cotard's syndrome appeared after 3 years from a tragic event that had caused a psychological trauma. Such an occurrence may have contributed to worsening OCD and leading to a second major depressive episode followed by a suicidal attempt. Since then, the subject of our patient's obsessive thoughts changed, and the belief of being dead appeared. The repetitive and stereotyped thoughts caused severe distress, and accompanied the compulsive nature of reassurance seeking, temporarily beneficial to the anxiety arousing. The transition from obsession to delusion occurred when resistance was abandoned, and insight was lost. Once Cotard's syndrome had stabilised, OCD was no longer present. Additional distinctive features were the absence of psychiatric family history and the persistent nature of the affective psychosis. We concluded that Cotard's syndrome represented the evolution of the initial obsessive-compulsive disorder. Furthermore, we differentiated the clinical condition of our patient from other psychiatric diseases with similar clinical features. Larger-scale research is needed to consider topics other than comorbidity and also to explore significant elements of the patient's clinical history to discover what may influence the evolution and/or the persistence of the diseases.

Delirium and Cognitive Impairment as Predisposing Factors of COVID-19 Infection in Neuropsychiatric Patients: A Narrative Review.

SARS-CoV-2 neuroinvasive and neurotropic abilities may underlie delirium onset and neuropsychiatric outcomes. Only a limited number of studies have addressed the potential effect of SARS-CoV-2 infection on mental health so far. Most studies mainly reported the acute onset of mixed neuropsychiatric conditions in patients infected with SARS-CoV-2, characterized by agitated behavior, altered level of consciousness, and disorganized thinking, regardless of psychological or socioeconomic triggering factors. The present narrative review aims to analyze and discuss the mechanisms underlying the neuroinvasive/neurotropic properties of SARS-CoV-2 and the subsequent mental complications. Delirium appeared as a clinical manifestation of SARS-CoV-2 brain infection in some patients, without systemic or multiple organ failure symptoms. A small number of studies demonstrated that neuropsychiatric symptoms associated with COVID-19, initially presenting as a confused state, may subsequently evolve in a way that is consistent with the patients' neuropsychiatric history. A literature analysis on this topic prevalently showed case reports and case series of patients presenting delirium or delirium-like symptoms as the main outburst of COVID-19, plus a cognitive impairment, from mild to severe, which pre-existed or was demonstrated during the acute phase or after infection. Dementia appeared as one of the most frequent predisposing factors to SARS-CoV-2 infection complicated with delirium. Instead, contrasting data emerged on the potential link between COVID-19 and delirium in patients with cognitive impairment and without a neuropsychiatric history. Therefore, clinicians should contemplate the possibility that COVID-19 appears as delirium followed by a psychiatric exacerbation, even without other systemic symptoms. In addition, cognitive impairment might act as a predisposing factor for COVID-19 in patients with delirium.

How do relatives cope with eating disorders? Results from an Italian multicentre study.

OBJECTIVE: This paper aims to: (1) describe coping strategies in relatives of patients with eating disorders (EDs); (2) analyze coping strategies according to the different EDs; (3) identify correlations between patients' clinical characteristics, relatives' socio-demographic characteristics and coping strategies. METHODS: Patients and their relatives consecutively attending three outpatient units for EDs at the Universities of Naples SUN, Salerno and Catanzaro were recruited. Coping strategies were assessed through the Family Coping Questionnaire for Eating Disorders (FCQ-ED). It consists of 32 items, grouped into two factors: problem-oriented ("seek for information", "positive communication") and emotion-focused ("avoidance," "collusion," "coercion") strategies, plus one item on seeking for spiritual help. RESULTS: Seventy-two patients and 127 relatives were recruited. The most frequently reported coping strategies by relatives were seeking for information, positive communication, seeking for spiritual help; the first two coping strategies were positively correlated with the level of education of both patients and relatives. Mothers reported avoidance less frequently than other relatives. Relatives of patients with BN reported collusion and coercion more frequently compared to relatives of patients with AN. DISCUSSION: This report represents an initial attempt to understand the complex relationship among clinical, social and personal variables involved in the development of coping strategies. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:587-592).

Social contacts and loneliness in people with psychotic and mood disorders.

BACKGROUND: Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions. METHODS: 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness. RESULTS: Patients had on average 1.7 (SD=1.7) social contacts in the previous week (median=1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n=30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR=2.246, p=.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR=2.798; p<.05). CONCLUSIONS: Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process.

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients.

The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.

Reading group rehabilitation for patients with psychosis: a randomized controlled study.

OBJECTIVE: Group reading activities are often reported to be helpful in a variety of psychiatric conditions. However, data on the effects of structured reading rehabilitation activities, in both hospital and community settings for patients with psychosis, are still scarce. Our aim was to investigate the effects on clinical status, disability, psychosocial functioning and cognitive functioning of a structured group reading activity, in a sample of hospitalized patients with psychosis. METHODS: We enrolled 41 consecutive patients with psychosis and randomly assigned them to a structured group reading programme. For all included patients, we psychometrically evaluated clinical symptomatology, psychosocial functioning and disability, as well as cognitive functioning. All evaluations were repeated at a 6-month follow-up. Repeated-measure multiple analyses of variance were used to test the effect of the group reading activities on the clinical, psychosocial and cognitive measures. RESULTS: We found that, after 6 months from discharge, structured group reading activities induced a statistically significant improvement of cognitive (p < 0.007) and psychosocial (p < 0.008) functioning in patients with psychosis and reduced their disability (p < 0.005), with respect to the control group. Furthermore, such programmes are easy to implement and were perceived as extremely 'interesting' and 'useful' by patients with psychosis. CONCLUSIONS: Rehabilitation programmes focusing on group reading activities should be regarded as a valid psychosocial rehabilitation tool for psychotic patients with severe mental disability. KEY PRACTITIONER MESSAGE: A structured group reading programme induced a significant symptomatological cognitive and psychosocial amelioration in hospitalized patients with psychosis. The improvement was sustained also at the 6-month follow-up, with respect to the control group. Structured group reading activities are perceived, by severely ill psychiatric patients, as highly useful, interesting and pleasant, while they are relatively easy to implement.

Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review.

BACKGROUND: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. METHODS: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. RESULTS: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). CONCLUSIONS: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders.

Duration of Untreated Illness in Patients with Obsessive-Compulsive Disorder and Its Impact on Long-Term Outcome: A Systematic Review.

Background: Duration of untreated illness (DUI)-defined as the time period between the onset of a mental disorder and its first adequate treatment-should influence patients' long-term prognosis and outcome. In patients with obsessive-compulsive disorder (OCD), DUI lasts on average from 87.5 up to 94.5 months, being significantly longer compared with data available from patients affected by other severe mental disorders, such as schizophrenia and bipolar disorder. We carried out a systematic review in order to assess the impact of DUI on long-term outcomes in OCD patients. Methods: A systemic review has been implemented, searching from inception to April 2023; only papers written in English were included. Results: Seventy-one articles were initially identified; only eight papers were included in the review. The DUI ranged from 7.0 ± 8.5 to 20.9 ± 11.2 years. Patients reporting a longer DUI have a poor long-term outcome in terms of lower level of treatment response and greater symptom severity. Conclusions: The present review confirms that longer DUI has a negative impact on the long-term outcome of patients with OCD. It should be useful to promote the dissemination of early interventions with a specific focus on OCD symptoms.

T Cell Responses to Dystrophin in a Natural History Study of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, but many patients have rare revertant fibers that express dystrophin. The skeletal muscle pathology of DMD patients includes immune cell infiltration and inflammatory cascades. There are several strategies to restore dystrophin in skeletal muscles of patients, including exon skipping and gene therapy. There is some evidence that dystrophin restoration leads to a reduction in immune cells, but dystrophin epitopes expressed in revertant fibers or following genome editing, cell therapy, or microdystrophin delivery after adeno-associated viral gene therapy may elicit T cell production in patients. This may affect the efficacy of the therapeutic intervention, and potentially lead to serious adverse events. To confirm and extend previous studies, we performed annual enzyme- linked immunospot interferon-gamma assays on peripheral blood mononuclear cells from 77 pediatric boys with DMD recruited into a natural history study, 69 of whom (89.6%) were treated with corticosteroids. T cell responses to dystrophin were quantified using a total of 368 peptides spanning the entire dystrophin protein, organized into nine peptide pools. Peptide mapping pools were used to further localize the immune response in one positive patient. Six (7.8%) patients had a T cell-mediated immune response to dystrophin at at least one time point. All patients who had a positive result had been treated with corticosteroids, either prednisolone or prednisone. Our results show that ∼8% of DMD individuals in our cohort have a pre-existing T cell-mediated immune response to dystrophin, despite steroid treatment. Although these responses are relatively low level, this information should be considered a useful immunological baseline before undertaking clinical trials and future DMD studies. We further highlight the importance for a robust, reproducible standard operating procedure for collecting, storing, and shipping samples from multiple centers to minimize the number of inconclusive data.

Second-Generation Antipsychotics' Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders.

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics' (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms.

Delirium and Psychiatric Sequelae Associated to SARS-CoV-2 in Asymptomatic Patients With Psychiatric History and Mild Cognitive Impairment as Risk Factors: Three Case Reports.

Human coronaviruses have neuroinvasive and neurotropic abilities that might explain psychiatric outcomes in affected patients. We hypothesized that delirium might be the sole clinical manifestation or even the prodrome of a psychiatric episode consistent with the mental history of a few infected patients with a preexisting diagnosed cognitive impairment. We examined three patients with preexisting mild cognitive impairment and delirium at admission for suspected SARS-CoV-2 infection. We diagnosed delirium using DSM-5 and Confusion Assessment Method (CAM) and measured consciousness level by the Glasgow Coma Scale. All the patients had no history of fever, respiratory complications, anosmia or ageusia, meningitis, and negative cerebrospinal fluid analysis for SARS-CoV-2. Our first patient had no psychiatric history, the second reported only a depressive episode, and the third had a history of bipolar disorder dated back to 40 years before. In the first patient, delirium resolved 2 days following the admission. The other two patients recovered in 4 and 14 days, and delirium appeared as the prodrome of a new psychiatric episode resembling past events. Clinicians should monitor the possibility that SARS-CoV-2 presence in the brain might clinically manifest in the form of delirium and acute psychiatric sequelae, even without other systemic symptoms. Psychiatric history and preexisting mild cognitive impairment are to be considered as predisposing factors for COVID-19 sequelae in delirium patients.

Vitamin D Deficiency and Risk Factors Related to Acute Psychiatric Relapses in Patients with Severe Mental Disorders: A Preliminary Study.

Previous studies have indicated that vitamin (Vit) D deficiency is frequent in psychiatric patients, regardless of diagnostic category. We aimed to assess whether acute psychiatric relapses in inpatients was associated with Vit D deficiency compared to stabilized outpatients. The cohort (152 total patients, 75 males and 77 females) had a mean age of 47.3 ± 14.4 years at admission and was grouped according to psychiatric diagnosis. Psychopathological symptom severity was assessed by the Brief Psychiatric Rating Scale (BPRS), a multidimensional symptom inventory. Total calcium serum levels were measured using standard laboratory methods, while plasma levels of 25-OH-Vit D and parathyroid hormone (PTH) were measured by automated chemiluminescence immunoassays. The psychiatric inpatient subgroup showed a significant difference in serum levels of 25-OH-Vit D and PTH (p < 0.001). Correlation analysis between serum levels of 25-OH-Vit D and BPRS total and subitem scores indicated a significantly negative relationship. In addition, linear regression analysis evidenced that the inpatient condition might predict low PTH and 25-OH-Vit D serum levels. Hospitalized psychiatric patients are at increased risk for Vit D deficiency regardless of their diagnostic categories. The mechanism underlying the association between acute psychiatric relapses and Vit D deficiency remains unclear. Therefore, screening for Vit D deficiency should pertain to the health assessment of patients with major psychiatric disorders.

A Multivariate Analysis of Depression Prevalence in Psoriasis Patients: A Cohort Study.

The literature reported higher depression rates in psoriasis patients compared to the general population. Our study aimed to verify whether variability in depression prevalence was due to using different diagnostic tools. We also aimed to determine whether dysfunctional coping strategies might increase the depression burden. We assessed psoriasis severity by the Psoriasis Area Severity Index (PASI) and PSOdisk. We analyzed mental alterations of 120 outpatients by Hamilton Depression and Anxiety Rating Scales (HAM-D and HAM-A), Symptom Checklist-90-Revised (SCL-90-R), plus coping strategies and quality of life by Coping Orientation to Problems Experienced (COPE) Inventory and 36-Item Short Form Health Survey (SF-36). We divided our cohort into five subgroups from minimal to severe psoriasis using the PSOdisk total score. Depression prevalence varied according to the assessment criteria for specificity, frequency, and severity. Different mood disorders other than major depression emerged when we used DSM-IV-TR criteria. Correlation analysis of the criteria we used to diagnose depression or depressed mood indicated that a dysfunctional coping strategy was highly and positively correlated only in patients of the severe subgroup. Differently, a negative correlation emerged between the SF-36 Mental Summary Component (MSC) and behavioral disengagement, thus suggesting that psychopathological distress might induce patients with a marked/severe psoriasis to adopt dysfunctional coping strategies. Dermatologists are fundamental in detecting comorbid depression, referring psoriasis patients to mental health specialists to achieve adequate treatments, and preventing suicide risk.

Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment.

Bipolar Patients and Bullous Pemphigoid after Risperidone Long-Acting Injectable: A Case Report and a Review of the Literature.

Neuropsychiatric disorders are found to be associated with bullous pemphigoid (BP), an autoimmune subepidermal blistering disease. Antipsychotics have emerged as possible inducing factors of BP. However, large sample studies concerning BP associated with antipsychotics, as well as with specific mental disorders, are still lacking. Our review retrieved a few clinical studies and case reports on the topic, producing controversial results. We report for the first time a bipolar patient case presenting BP following five-month therapy with risperidone long-acting injectable (LAI). We hypothesize that the dermatological event is associated with the medication administered. The issue emerged during psychiatric consultation and was confirmed by histological examination, direct and indirect immunofluorescence studies, plus positive plasma and cutaneous BP180 and BP230 IgG. Neurodegeneration or neuroinflammation might represent a primary process leading to a cross-reactive immune response between neural and cutaneous antigens and contributing to self-tolerance failure. Furthermore, the time sequence of the shared biological mechanisms leading to clinical manifestations of the neuropsychiatric disorder and BP remains undefined. BP comorbid with bipolar disorder might occasionally represent a serious health risk and affect patients' physical and psychosocial quality of life. Thus, clinicians treating psychiatric patients should consider BP as a possible adverse effect of psychotropic medications.

Duration of untreated illness predicts 3-year outcome in patients with obsessive-compulsive disorder: A real-world, naturalistic, follow-up study.

Duration of untreated illness (DUI) is a predictor of outcome in psychotic and affective disorders. The few available data on the effect of DUI in obsessive-compulsive disorder (OCD) suggest an association between longer DUI and poorer response to treatments. This is a real-world, naturalistic, follow-up study evaluating the impact of DUI on long-term clinical outcomes. The sample consists of 83 outpatients with OCD with a mean DUI of 7.3 (5.8) years. Patients with symmetry/ordering cluster symptoms were younger at onset of the disease (20.4 ± 7.9 vs. 27.8 ± 10.6; p<.05, d = 0.79), had a longer duration of the illness (10.1 ± 4.6 vs. 6.8 ± 4.6, p<.05; d = 0.53) and a longer DUI (7.9 ± 6.5 vs. 5.4 ± 3.6, p<.05, d = 0.49) compared to patients not presenting with those symptoms. Fifty-nine patients completed the follow-up, and 33.9% (N = 20) met the criteria for partial remission, scoring <15 at the Y-BOCS for at least eight weeks. Patients in partial remission for more than 40% of the follow-up were defined as "good outcome" and they had a significantly shorter DUI compared to patients with "poor outcome". Access to adequate treatments is highly delayed in patients with OCD. DUI is strongly associated with poor treatment outcomes. Therefore, strategies to ensure an early diagnosis and treatment are needed.