A reevaluation of mixed depressive states from the DSM-5- TR perspective: a series of prototypical cases.

Mixed depressive states are defined by the co-presence of depressive and manic symptoms. They represent extremely variable conditions from the point of view of clinical expressiveness and are difficult to recognize, ranging from clear schizophrenic-like psychoses and pseudodemented pictures to subsyndromal psychopathology. At the basis of the extreme variability of depressive pictures with mixed features are the different combinations that depressive and manic symptoms can assume. Furthermore, the intensity of depressive symptoms and manic symptoms, combined, can be variable, a factor that contributes to making the picture even more variable. Each form of mixed depressive state therefore presents its own specific symptomatic characteristics and specific difficulties in differential diagnosis and each form requires a different therapeutic strategy. In this work we have distinguished four possible specific subtypes of mixed depressive states, describing their specific clinical presentation and the therapeutic options most supported by the literature with the aim of contributing to a better recognition of mixed depressive states, to avoid incorrect diagnoses at patient and treatments that are useless if not worsening.

Silent Infections are not So Silent: The Emerging Role of Combined Infections, Inflammation, and Vitamin Levels in OCD.

Objective: Recent evidence highlights that different agents may trigger immune-mediated processes involved in the pathophysiology of different neuropsychiatric conditions. Given the limited information on obsessive-compulsive disorder (OCD), the present study aimed at assessing current/past infections and plasma levels of vitamin D, vitamin B12, folic acid, homocysteine and common peripheral inflammatory markers in a group of OCD outpatients. Method: The sample included 217 adult outpatients with an OCD diagnosis according to the DSM-5 criteria. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess the clinical phenotype and symptom severity. Laboratory blood tests measured levels of vitamin D, vitamin B12, folic acid, homocysteine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count and antibodies titers for cytomegalovirus (CMV), Epstein Barr virus (EBV), Toxoplasma gondii and antistreptolysin titer. Results: Sixty-one patients had a previous EBV infection, 46 were seropositive for CMV IgG, 24 showed positive antistreptolysin titer, 14 were seropositive for Toxoplasma gondii IgG, and four for CMV IgM. More than a half of patients showed vitamin D insufficiency. Compared to seronegative patients, patients with a past EBV infection displayed significantly higher scores on the Y-BOCS total score and compulsion subscale, and other symptoms. Vitamin D was negatively correlated with both the Y-BOCS total score and the subscales scores. Folic acid was negatively correlated with the Y-BOCS total and obsessions subscale score. Conclusions: The findings of our study show an association between Epstein-Barr infection and hypovitaminosis D and the overall severity and specific symptom patterns of OCD. The laboratory measures used in this study are useful, cheap and easy parameters that should be routinely assessed in patients with OCD. Further studies are needed to clarify their role in OCD pathophysiology and outcomes, as well as the potential therapeutic impact of vitamins and antibiotics/immunomodulatory agents in OCD and other psychiatric conditions.

Autistic Traits and Somatic Symptom Disorders: What Is the Link?

Alterations in sensory processing, a key component of autism spectrum disorder (ASD), have recently attracted increasing attention as they result in peculiar responses to sensory stimuli, possibly representing a risk factor for the development of somatic symptom disorder (SSD). Contextually, other features also associated with ASD, such as alexithymia, camouflaging and altered verbal, and non-verbal communication, have been suggested to represent risk factors for the occurrence and worsening of somatic symptomatology. The aim of this work was to review the available literature about the association between SSD and the autism spectrum. The results highlighted not only a higher prevalence of autistic features in patients suffering from SSD and a higher prevalence of reported somatic symptomatology in subjects with ASD but also how ASD subjects with co-occurrent somatic symptoms exhibit more severe autism-linked symptomatology. From the paper reviewed also emerged many shared features between the two conditions, such as alexithymia, altered sensitivity to sensory stimuli, cognitive inflexibility, intolerance of uncertainty, and an increased risk of experiencing stressful life events, which may provide an explanation for the correlation reported. Even though studies on the topic are still scant, the evidence reported suggests the importance of further assessing the correlation between the two disorders.

Admixture Analysis of Age of Onset in Bipolar Disorder and Impact of Anxiety Comorbidity.

BACKGROUND:  The present study aimed to examine clinical differences between subjects with early-onset (<21 years) and adult-onset (>30 years) bipolar I disorder, in particular, in relation to anxiety comorbidity. METHOD: Subjects were selected from a cohort of 161 consecutive patients with bipolar disorder type I as diagnosed by the Structured Clinical Interview for DSM Disorder (SCID-I). Clinical characteristics and axis I comorbidity were compared between those whose illness first emerged before the age of 21 years (n=58) and those whose first episode occurred after the age of 30 years (n=27). Psychopathology was assessed using the 18-item version of the Brief Psychiatric Rating Scale (BPRS). The frequency of delusions, hallucinations, and formal thought disorders was evaluated with the SCID-I. Overall, social and occupational functioning was assessed by the Global Assessment of Functioning (GAF). RESULTS: Most subjects with early-onset bipolar disorder were males, had panic disorder and substance abuse comorbidity, longer duration of illness, exhibited mood-incongruent delusions, and presented with a mixed episode at onset more frequently than the later adult-onset subjects. Mixed mania at the first episode of illness and lifetime panic disorder comorbidity predicted mixed polarity at the first hospitalization episode in the early-onset subjects. CONCLUSIONS: Overall, early age at onset seems to delineate a distinct bipolar I disorder subtype characterized by a greater likelihood of mixed episodes, lifetime panic disorder comorbidity, and schizophrenia-like delusions.

Post-traumatic Stress and Depressive Symptoms in Women With Ovarian Cancer 3-6 Months After Diagnosis.

BACKGROUND/AIM: The potentially traumatic role of severe life-threatening medical conditions is still debated in psychiatry and not yet recognized, particularly among post-traumatic stress disorders. However, increasing evidence suggests the psychopathological impact of severe medical conditions related to their poor prognosis, high lethality, treatments heaviness and invasiveness. Ovarian cancer (OC) is one of the malignancies with the highest mortality and the aim of this study was to investigate post-traumatic stress and depressive symptoms in women 3 to 6 months after diagnosis. PATIENTS AND METHODS: A sample of 83 women diagnosed with OC at different stages (from AI to IV) was recruited and assessed by means of the: Structural Clinical Interview for Mental Disorders according to DSM-5 (SCID-5), Trauma and Loss Spectrum Self-Report (TALS-SR), Impact Event Scale-Revised (IES-R), Hamilton Rating Scale for Depression (HAM-D), Mood Spectrum-Self Report (MOOD-SR), Work and Social Adjustment Scale (WSAS). RESULTS: Full data on the psychiatric assessments were available for 45 patients: 13 (28.9%) patients reported a diagnosis of PTSD. Patients with PTSD reported statistically significant higher depressive symptoms and more severe impact on work and social functioning compared to those without PTSD. CONCLUSION: Our results highlight the need to carefully assess the potentially traumatic burden of a diagnosis of OC and its association with depressive symptoms for their impact on patients' global functioning, in order to provide appropriate preventive and therapeutic interventions.

Rumination and altered reactivity to sensory input as vulnerability factors for developing post-traumatic stress symptoms among adults with autistic traits.

OBJECTIVE: Recent literature has suggested that individuals with autism spectrum disorder (ASD) or autistic traits (ATs) would be more likely to encounter traumatic events in their lifetime and to develop post-traumatic stress disorder (PTSD). However, the nature of this relationship has not yet been fully elucidated. The aims of this study were to evaluate the relationship between AT and PTSD and to investigate which specific autistic dimension was more associated with trauma and stress-related symptoms. METHODS: A total of 68 subjects with ASD and 64 healthy controls (HCs) were assessed with the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Trauma and Loss Spectrum (TALS) questionnaires. Statistical analyses included Mann-Whitney U test, chi-square test, calculation of Spearman's coefficients, and logistic regression analysis. RESULTS: Patients with significant AT reported a 30% rate of PTSD and higher TALS total and domain scores than HCs, among whom no PTSD was found instead. Significant positive correlations were reported between AdAS Spectrum and TALS-SR scores in the whole sample. AdAS Spectrum total scores were statistically predictive of the presence of PTSD. High scores at AdAS Spectrum Inflexibility and adherence to routine and Restrictive interest and rumination domains were identified as positive predictors of a probable PTSD. CONCLUSION: Compared to HCs, subjects with significant AT are more likely to present symptoms of PTSD. In particular, AT related to ruminative thinking, narrow interests, and sensorial reactivity would seem to predict the presence of post-traumatic stress symptomatology.

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug.

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms "Clozapine indications", "Clozapine adverse effects", "Clozapine regenerative effects", and "Clozapine neuroplasticity" with the aim of reviewing the scientific literature on Clozapine's treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management.

Autistic Traits as Predictors of Increased Obsessive-Compulsive Disorder Severity: The Role of Inflexibility and Communication Impairment.

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive-Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions.

Case report: Familial case with autism spectrum and bipolar disorder showing a 20q11.21 microduplication including TM9SF4.

Autism spectrum disorder (ASD) is characterized by multifactorial etiology and high heritability but can be challenging to be diagnosed, especially in cases presenting subthreshold symptoms with no cognitive or language impairment, which may not be identified until adulthood but may occur in family members of subjects with ASD. This study explores the possible correlation between a genomic imbalance and clinical phenotypes in a family case of a proband with ASD, with subjects presenting full-blown or subthreshold ASD and/or mood disorders. Clinical assessments were carried out by means of the Structured Clinical Interview for DSM-5 (SCID-5) disorders, Autism Spectrum Quotient (AQ), Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule Module 2 (ADOS-2), and Adult Autism Subthreshold Spectrum (AdAS Spectrum). The genetic evaluation included array comparative genomic hybridization (array-CGH). The proband was diagnosed with ASD and bipolar disorder type I (BD-I), her twin brothers with ASD and intellectual disability (ID), and her father and sister with BD type II (BD-II) and autism traits. The proband, her father, twin brothers, and older sister showed a microduplication of 350 kb in 20q11.21. In contrast, the proband's mother did not present the microduplication or any mental disorder. This study reports a microduplication that segregates with family members affected by ASD or autistic traits comorbid in some cases with bipolar disorder, and that has never been reported in healthy subjects. Among the genes harbored in this region, the TM9SF4 gene has been recently implicated in risk for ASD.

Physical activity influences adherence to pharmacological treatments in patients with severe mental disorders: results from the multicentric, randomized controlled LIFESTYLE trial.

Introduction: Poor adherence to pharmacological treatment is frequent in people with severe mental disorders and it often causes lack of effectiveness of many psychotropic drugs. Thus, efforts should be made to improve adherence to pharmacological treatments in patients with these disorders. Methods: In this paper, based on the LIFESTYLE randomized, controlled multicentric trial, we aim to: 1) assess the level of adherence in a real-world sample of patients with severe mental disorders; 2) evaluate differences in treatment adherence according to patients' socio-demographic and clinical characteristics; 3) evaluate the impact of an innovative psychosocial intervention, on patients' adherence to treatments. The Lifestyle Psychosocial Group Intervention consists of group sessions, focused on different lifestyle behaviours, including healthy diet; physical activity; smoking habits; medication adherence; risky behaviours; and regular circadian rhythms. At end of each session a 20-min moderate physical activity is performed by the whole group. Results: The sample consists of 402 patients, mainly female (57.1%, N = 229), with a mean age of 45.6 years (±11.8). Less than 40% of patients reported a good adherence to pharmacological treatments. Adherence to treatments was not influenced by gender, age, diagnosis and duration of illness. At the end of the intervention, patients receiving the experimental intervention reported a significant improvement in the levels of adherence to treatments (T0: 35.8% vs. T3: 47.6%, p < 0.005). Patients practicing moderate physical activity reported a two-point improvement in the levels of adherence [odds ratio (OR): 1,542; 95% confidence intervals (CI): 1,157-2,055; p < 0.001], even after controlling for several confounding factors. Discussion: The experimental lifestyle intervention, which can be easily implemented in the routine clinical practice of mental health centres, was effective in improving adherence to pharmacological treatments.

Post-traumatic stress disorder and post-traumatic stress symptoms in patients with systemic autoimmune diseases during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 outbreak led to an increase in mental disorders, particularly post-traumatic stress disorder (PTSD), in the general population and especially in high-risk populations such as patients with rheumatologic conditions. Although these latters are considered vulnerable to developing PTSD, few specific data have been particularly reported in the framework of the pandemic. The aim of the present study was to investigate PTSD and post-traumatic stress symptoms (PTSS) in a sample of patients with systemic autoimmune disease (SAD), followed in the framework of a prospective observational study during the pandemic. METHODS: The PERMAS project is a prospective observational study including patients with SAD and involving the Rheumatology and the Psychiatric Clinics of the Azienda Ospedaliero Universitaria Pisana (AOUP, Pisa, Italy) and the Institute of Management of the Scuola Superiore Sant'Anna (Pisa, Italy). The assessments included: a data-sheet for sociodemographic and clinical characteristics; the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), for PTSD and PTSS; the 36-item Short Form Survey (SF-36) to assess quality of life. RESULTS: The total sample consisted of 252 patients with SAD, including 131 with connective tissue disease, 101 with arthritis and 20 with systemic vasculitis. The diagnostic groups differed significantly in age (p<0.001), gender (p<0.001), prevalence of full-blown and partial PTSD (p=0.001), and other psychopathologic variables. Connective tissue disease and SF-36 were significantly associated with the TALS-SR scores in both univariate (p<0.001) and multivariate (p<0.025; p<0.001) analyses. CONCLUSIONS: Patients with SAD, and, in particular, patients with connective tissue diseases reported an increased risk of developing stress-related psychopathological symptoms, indicating the need for special psychological monitoring of this high-risk group.

Implications of Social Anxiety Symptoms in Adults with Autism Spectrum Disorder: Is There a Predictive Role of Interpersonal Sensitivity and Substance Abuse?

Social anxiety disorder (SAD) has been frequently reported by subjects with Autism Spectrum Disorder (ASD). However, interestingly, the overlap between social anxiety and autistic traits may sometimes impede ASD diagnosis in subjects without intellectual or language impairment. The aim of the present work was to evaluate the presence and correlates of social phobic features among subjects with ASD, with a specific focus on evaluating which social anxiety symptoms may be statistically predictive of an ASD diagnosis. With this purpose, 48 subjects with ASD and 48 gender- and age- matched healthy controls (HCs) were recruited and assessed with the SHY-SV and the AdAS Spectrum questionnaires. Results highlighted higher scores in all SHY-SV Spectrum domains and total scores for the ASD group. Moreover, AdAS Spectrum scores were significantly correlated with all SHY-SV domain and total scores. A logistic regression analysis highlighted the SHY-SV Interpersonal sensitivity and Substance Abuse domains scores as significant positive predictors of an ASD diagnosis. These results confirm the link between ASD and SAD. Because of this association, particular attention should be paid to subjects with high interpersonal sensitivity traits and substance abuse problems.

Emotional dysregulation as a part of the autism spectrum continuum: a literature review from late childhood to adulthood.

The concept of emotional dysregulation (ED) has recently gained interest in the scientific literature and is commonly defined as the inability to use the modulatory mechanisms involved in emotion regulation, resulting in a functioning meaningfully below the baseline. Even though the data available are still limited, an increasing number of studies have hypothesized a promoting role for some of the core features of autism spectrum disorder (ASD) in the development of ED, in particular being repetitive behaviors, social difficulties and alexythimia. In this framework, the purpose of this study was to review the literature that is currently available about presence and correlates of ED in young adults with autism spectrum conditions as well as to offer some insights about possible implications for illness trajectories. The data reported seems to point to a shared etiology between ED and repetitive/restricted ASD symptoms, with perseveration features serving as the foundation for the inability to control one's emotions. In this context, a neurodevelopmental basis for ED could be consistent with the transnosographic conceptualization of ASD, which hypothesizes a potential neurodevelopmental basis for several psychiatric disorders, whose autistic traits would be the phenotypical presentation.

Measuring the neglected anxiety disorder: validation of the social anxiety spectrum-short version (SHY-SV) questionnaire.

BACKGROUND: In the recent years, a growing body of literature stressed the importance of a dimensional perspective on mental disorders. In particular, since its conceptualization, one of the main concerns in the field of Social Anxiety Disorder (SAD) has been the definition of a diagnostic threshold, leading to the suggestion that SAD may be more properly classified as a spectrum of severity rather than a discrete disorder based on subjectively determined threshold. The purpose of the current research is to evaluate the psychometric qualities of the Social Anxiety Spectrum - Short Version (SHY-SV), a novel questionnaire designed to measure the complete range of social anxiety symptoms, from overt manifestations to subthreshold ones. METHODS: 42 subjects with a clinical diagnosis of social anxiety disorder (SAD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 43 subjects with a clinical diagnosis of Obsessive-Compulsive Disorder (OCD) and 60 individuals without current or lifetime mental disorders (HC) were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, Liebowitz Social Anxiety Scale (LSAS) and the SHY-SV. RESULTS: SHY-SV showed strong internal consistency, and both the total and domain scores had great test-retest reliability. The Pearson's coefficients for the SHY-SV domain scores ranged from 0.391 to 0.933, and they were positively and significantly correlated with one another (p 0.001). All the SHY-SV domain scores were highly correlated with the SHY-SV total score. Results from of the correlation coefficients between SHY-SV and alternative measures of SAD were all significant and positive. Significant differences among diagnostic groups on both SAD-SV domains and total scores were found. SAD-SV total score increased significantly and progressively from HCs, to the OCD up to the SAD group which showed the highest values. CONCLUSION: The SHY-SV demonstrated significant convergent validity with other dimensional SAD measures, great internal consistency, and test-retest reliability. With an increasing score gradient from healthy controls to patients with OCD to those with SAD, the questionnaire performed differently in each of the three diagnostic categories.

Relationship between BDNF and oxytocin.

Converging, albeit scattered data mainly gathered in animals indicate that the neurotrophin brain-derived neurotrophic factor (BDNF) and the nonapeptide oxytocin (OT) interact in a cooperative way. Data in humans are really limited and indirect. Therefore, the aim of the present study was to explore the possible existence of a link between OT and BDNF in humans, by means of two peripheral markers, the platelet-poor-plasmatic-BDNF (PPP-BDNF) and the platelet BDNF (PLT-BDNF) and OT levels. Twenty-six young healthy controls of both sexes who volunteered for the study were included in the study. Fifty ml of peripheral venous blood were drawn from one-night fasting subjects between 8.00 and 9.00 a.m. The BDNF and OT assays were carried out according to common methods. Comparisons for continuous variables were performed by the Student's t-test for variables that follow a normal distribution, and by the Wilcoxon-Mann-Whitney test for variables not normally distributed. The correlations between biological markers were explored by calculating the Pearson's correlation coefficient or Spearman's rank correlation. The results showed that PLT-BDNF (pg/mg proteins, mean ± SD) and PPP-BDNF (pg/ml, mean ± SD) were 1546 ± 1844 and 10111 ± 1892, respectively. The OT levels (pg/ml, mean ± SD) were 13.92 ± 4.54. The OT levels were significantly higher in women than in men. The Spearman's analysis revealed a statistically significant and negative correlation between OT levels and PLT-BDNF (R = -0.543, p = 0.004). The findings of this study highlight the presence of a significant and negative correlation between OT and PLT-BDNF in a small group of healthy controls of both sexes. In any case, despite all the limits of peripheral biomarkers, they suggest that this reciprocal influence might have a downstream homeostatic function dampening one activity when the other is activated or no longer necessary, maybe at the level of the stress and/or immune systems.

Autistic symptoms in unaffected first-degree relatives of people with schizophrenia: results from the Italian Network for Research on Psychoses multicenter study.

BACKGROUND: Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed. METHODS: A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures. RESULTS: Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory (p = 0.014) and Social Cognition (p = 0.025) domains and in the Global Cognition composite score (p = 0.008), as well as worse on functional capacity (p = 0.001), global psychosocial functioning (p < 0.001), real-world interpersonal relationships (p < 0.001), participation in community activities (p = 0.017), and work skills (p = 0.006). CONCLUSIONS: A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives.