Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with autism spectrum disorder and their first-degree relatives.

BACKGROUND: Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms. METHODS: A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects. RESULTS: ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables. CONCLUSIONS: Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.

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.

An attempted "suicide pact" in Covid-19 era - psychiatric perspectives.

BACKGROUND: A "suicide pact" is a joint and actively induced death of two individuals with the essential and unavoidable characteristic of a mutual consent. One of the partners (dominant in the relationship, commonly male) usually induces the action and in most cases, it is the one who actively carries it out. Undiagnosed psychopathological dimension or pathological subthreshold traits are found in those who enter into suicide agreements, the presence of cluster B personality traits such as narcissistic or borderline is of particular relevance in the dominant partner, while in the submissive one dependent personality traits are more frequent. As in the case of other similar health emergencies, COVID-19 pandemic seems to lead to greater suicidality, including the "suicide pacts" of couples whose motivation varies including firstly financial problems, strictly followed by fear of infection and not being able to return home from abroad. CASE PRESENTATION: We reported a case of a couple who entered a suicide agreement consequently to the economic difficulties caused by COVID-19 pandemic, hospitalized in our department. Both partners were assessed with Adult Autism Subthreshold Spectrum (AdAS Spectrum) and both crossed the threshold for clinically relevant autistic traits (M = 67; F = 49). CONCLUSION: This case further confirms the link between COVID-19 pandemics and suicidality. The role of autism spectrum traits as a vulnerability factor towards the development of severe psychopathological consequences after traumatic events is also stressed.

Orthorexia and autism spectrum in University workers: relationship with gender, body mass index and dietary habits.

OBJECTIVE: To date, few studies have investigated the relationship between autistic traits and emerging phenotypes of restrictive disorders, such as Orthorexia nervosa (ON). The aim of the present work was to investigate the relationship between ON symptoms and autistic traits in a population of University employees, focusing on the impact of gender, weight and type of diet. METHODS: All academic and technical/administrative workers of University of Pisa were invited by mail to fulfil through an anonymous online form the Adult Autism Sub-threshold Spectrum (AdAS Spectrum) and the ORTO-R. RESULTS: A total of 285 subjects filled out the questionnaires. Participants with significant autistic traits were included into the Broad autism phenotype (BAP) group, while others into the No BAP group. Subjects in the BAP group reported significantly higher ORTO-R scores than others, while no difference was reported for gender, work position, type of diet, age and BMI. Females showed significantly higher ORTO-R scores and lower BMI than males. Older subjects showed a higher BMI. No significant differences in ORTO-R scores were reported depending on type of diet and work position. A decision tree model, with ORTO-R score as dependent variable, revealed in the first step significantly higher ORTO-R scores in the BAP group than in the No BAP group, and in the second step significantly higher ORTO-R scores among females only in the No BAP group. CONCLUSION: Our results further confirm the association between ON and autism spectrum, which seems to overcome the impact of gender in this population. LEVEL OF EVIDENCE: Level V, descriptive study.

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.

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.

Major Depressive Disorder with Catatonia: A Phenotype Related to Autistic Traits and High Suicidality.

Background: Major Depressive Disorder (MDD) represents a significant global health concern, often complicated by comorbidities such as catatonia and autism spectrum disorder (ASD). Recognizing the interplay among these conditions and their impact on suicidal tendencies is crucial for effective clinical management. Methods: A total sample of 147 subjects with MDD was divided into Significant Catatonia (SC) and Non-Significant Catatonia (NSC) groups based on Catatonia Spectrum (CS) scores. Participants were evaluated through the Structured Clinical Interview for DSM-5, Research Version (SCID-5-RV), the Adult Autism Subtreshold Spectrum (AdAS Spectrum), and the Mood Spectrum-Self Report questionnaires. Statistical analyses included Mann-Whitney U test, Chi-square test, logistic regression analyses, and a decision tree model. Results: The SC group exhibited higher CS, AdAS Spectrum, and MOODS-SR total and domain scores compared to the NSC group. Individuals with significant autistic traits were over-represented in the SC group, as well as participants with higher suicidality, suicidal ideation, and a history of suicide attempts. The total AdAS Spectrum and MOOD-SR score, the AdAS domain "Hyper-hypo reactivity to sensory input", and the "Cognitive depressive" MOOD-SR domain were predictive of belonging to the SC group. Suicidality levels appeared to be higher in clinically significant ASD, intermediate in subjects with autistic traits (AT), and low in the absence of AT. Conclusions: the study suggests the existence of a specific phenotype of MDD associated with catatonia, characterized by elevated autistic traits and suicide risk.

Assessing Autistic Traits, Hikikomori Tendencies, Pathological Videogaming, and Eating Disorders in University Students: Are Pathological Videogaming and Eating Disorders Gender-Specific Manifestations of the Autism Spectrum?

In the previous literature, specific attention has been paid to investigate autism spectrum symptoms and traits in university students. In this framework, we aimed to evaluate the presence and correlates of autistic traits, hikikomori tendencies, altered eating behaviors, and pathological videogaming in a sample of Italian university students enrolled in bachelor's degree courses. A total of 1192 students were recruited via an online survey and assessed with the Hikikomori Questionnaire-25, the Adult Autism Subthreshold Spectrum Questionnaire, the Eating Attitude test-26, and the Assessment of Internet and Computer Game Addiction. Our results highlighted significant differences in the prevalence of autistic traits, social withdrawal tendencies, altered eating habits, and pathological videogame use in university students based on gender, age, parents' level of instruction, and field of study. A significant effect of the presence of autistic traits and gender on the scores obtained with the other questionnaires was reported. Our results not only support the role of autistic traits as a vulnerability factor for the development of a set of psychopathological conditions but also suggest that gender could modulate this vulnerability, supporting the hypothesis of gender-specific phenotypes in the autism spectrum.

Video Gaming in Older People: What Are the Implications for Cognitive Functions?

Mild cognitive impairment impacts a sizable segment of the older population, and often evolves into dementia within a few years. At this stage, subjects may benefit from non-pharmacological therapies that can delay or stop the progression of the mild cognitive impairment into dementia and are crucial for improvement in the subject's quality of life, while also being easily accessible and safe for use. Many research studies have shown that a variety of exercises, including cognitive training, have the potential to enhance or optimize cognitive function and general well-being. Recently, many authors have suggested video games as a promising approach for cognitive training and neurorehabilitation in older people, thanks to their increasing motivation and training effects through immersion in stimulating environments. Under this premise, our narrative review's objective is to discuss and summarize the body of existing material on the role of video games in improving cognitive performance, daily life activities, and depression symptoms in older individuals with different levels of cognitive decline. From the papers reviewed, it emerged that older subjects trained with video games showed a significant improvement in cognitive functions, sleep quality, and psychiatric symptoms, positioning video games as an intriguing and useful tool.

Platelet Levels of Brain-Derived Neurotrophic Factor in Adults with Autism Spectrum Disorder: Is There a Specific Association with Autism Spectrum Psychopathology?

To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact that circulating BDNF is stored in platelets and released into the circulation when needed. To the best of our knowledge, a very limited number of studies have related peripheral BDNF values to platelet counts, and yet no study has evaluated intra-platelet BDNF levels in adults with ASD. In this framework, the aim of the present work is to pave the way in this field and evaluate platelet BNDF levels in adult ASD patients, as well as their correlation with autistic symptoms and related psychopathological dimensions. We recruited 22 ASD and 22 healthy controls, evaluated with the Adult autism subthreshold spectrum (AdAS Spectrum), the Social Anxiety Spectrum-self report (SHY-SR), the Trauma and loss spectrum-self report (TALS-SR), the Work and Social Adjustment Scale (WSAS), and the Mood Spectrum-self report for suicidality. Intra-platelet BDNF levels were also assessed. The results highlighted lower BDNF levels in the ASD group; moreover, AdAS Spectrum and WSAS total score as well as AdAS Spectrum Restricted interest and rumination, WSAS Private leisure activities, TALS-SR Arousal, and SHY-SR Childhood domains were significant negative predictors of platelet BDNF levels.

Case report: hikikomori syndrome in Italy and its link with autistic traits and internet gaming disorder.

During the last few decades, a growing field of literature is focusing on hikikomori, a phenomenon described as a form of pathological social withdrawal or social isolation that lasts for more than 6 months leading to significant functional impairment and/or distress. Despite initially considered a culture-bound syndrome, hikikomori syndrome later gained a wider recognition in different countries, ranging from an attempt to take refuge in an idealistic world, when society success' standards are not reached, to a maladaptive coping strategy complicating several psychiatric illnesses such as anxiety disorders, major depression, internet addiction, internet gaming disorder (IGD) and autism spectrum disorder (ASD). In this framework, difficulties in social interaction, in problem solving strategies and socio-emotional reciprocity, may lead to social withdrawal and hikikomori-like behaviors. In this work, we described two cases of patients where the presence of underlying autism spectrum may have represented a sign of vulnerability towards the development of a possible full-blown case of hikikomori with IGD.

Autistic traits as predictors of post-traumatic stress symptoms among patients with borderline personality disorder.

Background: Autistic traits (AT) seem to be particularly frequent among patients with borderline personality disorder (BPD). Moreover, the autism spectrum is considered a vulnerability factor for the development of post-traumatic stress disorder (PTSD) symptoms, increasing the vulnerability of BPD subjects toward the development of a stress-related disorder. Aim: The study aimed to investigate the association between AT and trauma-related symptoms in a clinical sample of patients with BPD. Methods: A total of 48 patients with a clinical diagnosis of BPD and 52 healthy control (HC) subjects were recruited and assessed with the Adult Autism Subthreshold Spectrum Self-Report (AdAS Spectrum) questionnaire and the Trauma and Loss Spectrum-Self-Report questionnaire (TALS-SR). The BPD group was divided into two subgroups: BPD with a symptomatological diagnosis of PTSD (pBPD = 25) and BPD not diagnosed with PTSD (No-pBPD = 23). Results: The clinical sample scored significantly higher in almost all AdAS domains. Moreover, pBPD groups reported higher AdAS and TALS-SR scores in the total and in various domains than the No-pBPD group, which scored higher in several domains than HC. AdAS Restricted interests and rumination domain scores were positive predictors of BPD presence independently from PTSD, while Inflexibility and adherence to routine domain was a negative predictor. Finally, AdAS Hyper/hyporeactivity to sensory stimuli domain was a positive predictor only for inclusion in the pBPD group. Conclusion: Our study confirmed the existence of a statistically significant relationship between the autism spectrum and BPD, while BPD subjects diagnosed with PTSD seem to show a higher autism spectrum burden.

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.

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.

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.

Measuring Social Camouflaging in Individuals with High Functioning Autism: A Literature Review.

In the recent years, growing attention has been paid to the use of camouflaging strategies by adult populations suffering from autism spectrum disorder (ASD) with milder manifestations and without intellectual impairment, which may lead to a delay in diagnosis or even a misdiagnosis. In fact, high-functioning ASD individuals were reported to be more aware of their communication difficulties and were more likely make considerable efforts to adjust their behavior to conventional rules of non-autistic individuals, learning to imitate other non-ASD individuals. Moreover, females reported a higher frequency of camouflaging strategies, suggesting a role of camouflaging in the gender gap of the ASD diagnosis. Although camouflaging strategies can sometimes grant a better level of adjustment, even resulting in a hyper-adaptive behavior, they are also often correlated with negative mental health consequences due to the long-term stress associated with continuous attempts to adapt in day-to-day life. In this framework, the aim of the present work was to review the available studies that assessed the presence and correlates of camouflaging strategies in individuals with ASD. Although the literature available on the topic is still scarce, some interesting correlations between camouflaging and anxious and depressive symptoms, as well as suicidality, were highlighted. In particular, the controversial and sometime opposite thoughts and results about camouflaging may be clarified and integrated in light of a dimensional approach to psychopathology.

Autism Spectrum Disorder in a Patient with Bipolar Disorder and Its Relationship with Catatonia Spectrum: A Case Study.

According to several studies, the prevalence of Autism Spectrum Disorder (ASD) ranges from 2.4 to 9.9 percent among adult mental inpatients. However, subjects with forms of ASD that fit in the high functioning spectrum may remain undiagnosed during childhood and adolescence without reaching clinical attention until they develop in adult life other psychiatric disorders, often characterized by treatment resistance and poor outcomes. The aim of this case report was to evaluate the role of an undiagnosed ASD in the mental illness trajectory and discuss the diagnostic and therapeutic implications. We reported a case of a young man with an undiagnosed ASD that came to clinical attention only after the development of a severe manic episode with mixed and psychotic features and with catatonia in adulthood, despite meeting DSM-5-TR (APA, 2022) diagnostic criteria for ASD since early childhood. This case confirms the need of a timely identification of ASD in order to prevent the development of a mental illness trajectory and to improve the prognosis and the outcome. Moreover, on the heuristic level, this case seems to support the presence of a continuum between ASD and catatonia. In this framework, the use of a questionnaire based on a spectrum model, such as the AdAS Spectrum, could be useful in early diagnosis of ASD without intellectual or language impairment as well as in early detection of subthreshold conditions (broad autism spectrum phenotype or autistic traits), which represents a vulnerability factor for the development of various mental disorders.

Neuroprotective properties of antiepileptics: what are the implications for psychiatric disorders?

Since the discovery of the first antiepileptic compound, increasing attention has been paid to antiepileptic drugs (AEDs), and recently, with the understanding of the molecular mechanism underlying cells death, a new interest has revolved around a potential neuroprotective effect of AEDs. While many neurobiological studies in this field have focused on the protection of neurons, growing data are reporting how exposure to AEDs can also affect glial cells and the plastic response underlying recovery; however, demonstrating the neuroprotective abilities of AEDs remains a changeling task. The present work aims to summarize and review the literature available on the neuroprotective properties of the most commonly used AEDs. Results highlighted how further studies should investigate the link between AEDs and neuroprotective properties; while many studies are available on valproate, results for other AEDs are very limited and the majority of the research has been carried out on animal models. Moreover, a better understanding of the biological basis underlying neuro-regenerative defects may pave the way for the investigation of further therapeutic targets and eventually lead to an improvement in the actual treatment strategies.