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.

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.

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.

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.

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.

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.

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.

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.

Autistic and Catatonic Spectrum Symptoms in Patients with Borderline Personality Disorder.

BACKGROUND: Recent literature has shown that a considerable percentage of patients with severe mental disorders can develop, over time, full-blown or subthreshold catatonia. Some studies corroborate the model of an illness trajectory in which different mental disorders would be arranged along a continuum of severity until the development of catatonia. In such an illness pathway, autistic traits (AT) and borderline personality disorder (BPD) may represent important steps. In order to further explore the association between AT, BPD, and catatonia, the aim of this study was to compare catatonic spectrum symptoms and AT among patients with major depressive disorder (MDD), BPD, and healthy controls (CTL), also evaluating possible predictive dimensions of the different diagnoses. METHODS: A total of 90 adults affected by BPD, 90 adults with a diagnosis of MDD, and 90 CTL, homogeneous in terms of gender and age, were recruited from six Italian university departments of psychiatry and assessed with the SCID-5-RV, the Catatonia Spectrum (CS), and the Adult Autism Subthreshold Autism Spectrum (AdAS Spectrum). RESULTS: The total CS score was significantly higher in the BPD and MDD groups than in the CTL group, while the majority of CS domain scores were significantly higher in the BPD group than in the MDD group, which scored significantly higher than the CTL group. The total AdAS Spectrum score and the AdAS Spectrum domain scores were significantly higher in the BPD group than in the MDD group, which in turn scored significantly higher than the CTL group. The CS domains "psychomotor activity" and "impulsivity", and AdAS Spectrum domains "verbal communication", "empathy", and "hyper-/hyporeactivity to sensory input" were associated with the risk of presenting a diagnosis of BPD.

The mediating effect of mood spectrum on the relationship between autistic traits and catatonia spectrum.

Background: In the recent years, several studies have shown a correlation between autism spectrum disorder (ASD) and catatonia. It is also known that both conditions are found to be associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum in the relationship between them. Methods: The total sample of 514 subjects was composed by four diagnostic groups, composed by patients affected by catatonia (CTN), borderline personality disorder (BPD), major depressive disorder (MDD) and healthy controls (HC). Subjects were assessed with the SCID-5-RV, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Catatonia Spectrum (CS) and the Mood Spectrum Self-Report (MOODS-SR). Statistical analyses included Pearson's coefficient calculation, multiple linear regression, and mediation analysis. Results: all the correlations appear to be strongly positive and significant with the strongest coefficient emerging between AdAS Spectrum total score and CS total score (r = 0.762, p < 0.001). The Mediation Analysis showed that AdAS Spectrum total score showed a significant indirect effect on CS total score through MOODS-SR total score (b = 0.168, 95% bootstrapped CI [0.127:0.207]). Conclusion: The present study highlights the presence of a mediating role of the mood disorder spectrum in the relationship between autistic traits and the catatonia spectrum.

Autism Spectrum, Hikikomori Syndrome and Internet Gaming Disorder: Is There a Link?

The aim of this study is to review the available literature investigating the relationship between hikikomori, a pathological condition characterized by severe social withdrawal or isolation, autism spectrum disorder (ASD) and Internet gaming disorder (IGD). Studies on the relationship between ASD and IGD have found significant positive correlations between these two conditions. Individuals with ASD would appear to be at risk of developing a problematic use of the Internet, which, to the right extent, would represent a useful tool for social interaction and cognitive development. Even subjects with hikikomori, in whom rarefied interpersonal relationships and social isolation could be balanced by the use of online connections, appear to be at high risk of developing IGD. On the other hand, the finding of significant autistic traits in populations with hikikomori could lead to considering this psychopathological condition as a particular presentation of autism spectrum, a hypothesis that requires further investigation.

Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients' Clinical Features.

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.

Validation of the short version of the obsessive compulsive spectrum questionnaire.

Aim: In the recent years, a rising amount of research has stressed the importance of a dimensional perspective on mental disorders. In particular, the conceptualization of an obsessive-compulsive spectrum appears to be in line with the very first descriptions of Obsessive-Compulsive Disorder and has been partially acknowledged by the inclusion of the "OCD-spectrum related syndromes and disorders" section in the DSM-5. The goal of the current study is to ascertain the psychometric characteristics of the Obsessive-Compulsive Spectrum-Short Version (OBS-SV), a novel questionnaire designed to measure the complete range of obsessive-compulsive symptoms, from severe full blown to subthreshold ones. Methods: Forty three subjects with a clinical diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); 42 subjects with a clinical diagnosis of social anxiety disorder (SAD), 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, the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the OBS-SV. Results: OBS-SV showed strong test-retest reliability for both the total and the domains scores, as well as a high level of internal consistency. The Pearson's coefficients for the OBS-SV domain scores ranged from 0.771 to 0.943, and they were positively and strongly linked with one another (p < 0.001). The OBS-SV total score had a strong correlation with each of the OBS-SV domain scores. All correlation coefficients between OBS-SV and additional measures of OCS were observed to be strong, significant and positive. Both OBS-SV domain and overall score differences between diagnostic groups were found to be statistically significant. From HCs, to the SAD, up to the OC group, which had the highest values, the OBS-SV total score grew dramatically and progressively. Conclusion: The OBS-SV demonstrated significant convergent validity with other dimensional OCD measures, excellent internal consistency, and test-retest reliability. Across the three diagnostic categories, the questionnaire functioned differently, with a rising score gradient from healthy controls through SAD patients to OCD subjects.

Investigating suicidality across the autistic-catatonic continuum in a clinical sample of subjects with major depressive disorder and borderline personality disorder.

Background: Recent literature has highlighted that catatonia may be more prevalent among psychiatric patients than previously thought, beginning from autism spectrum disorders (ASD), for which it has been suggested to represent a severe late consequence, but also among individuals with mood disorders and borderline personality disorder (BPD). Interestingly, one critical point shared by these conditions is the increased risk of suicidality. The aim of this study was to evaluate how the presence and the prevalence of catatonic symptoms may shape and correlate with suicidal risk in a sample of individuals with major depressive disorder (MDD) or BPD. Methods: We recruited two clinical samples of subjects (BPD and MDD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the catatonia spectrum (CS) and the MOODS-SR for evaluating suicidality. Results: In the total sample, suicidality score was significantly and positively correlated with all CS domains and CS total score. Correlation and regression analyses highlighted specific patterns of association among Catatonia spectrum domains and suicidality in the MDD and BPD group and in the total sample. Conclusion: In both disorders, higher catatonic traits are linked to higher suicidal tendencies, confirming the high risk of suicide for this population. However, different patterns of association between catatonic symptoms and suicidality were highlighted in the two disorders.

Autistic traits distribution in different psychiatric conditions: A cluster analysis on the basis of the Adult Autism Subthreshold Spectrum (AdAS Spectrum) questionnaire.

Increasing interest is being paid on full-threshold and sub-threshold autism spectrum conditions among adults. Sub-threshold autistic traits (AT) seem to be distributed in a continuum from the clinical to the general population, being particularly higher among subjects with other psychiatric disorders. The aim of the present study was to evaluate the distribution of AT in a sample of subjects with different psychiatric conditions by means of a cluster analysis on the basis of the score reported to the AdAS Spectrum instrument. A total of 738 subjects recruited by seven Italian Universities were divided in 5 groups depending on the clinical diagnosis: Autism spectrum disorder (ASD), subthreshold ASD symptoms (partial ASD), Bipolar disorder (BD), Feeding and eating disorders (FED), and controls (CTLs). All subjects were assessed with the AdAS Spectrum. The cluster analysis identified 3 clusters: the high, medium and low autism clusters. The Restricted interests and rumination domain reported the highest influence in forming the clusters. The high, medium and low autism clusters were respectively more represented in the ASD, partial ASD and CTL groups. The clusters were represented intermediately in the FED and BD groups, confirming the presence of intermediate levels of AT in these clinical populations.