Is the Hedgehog Pathway Involved in the Pathophysiology of Schizophrenia? A Systematic Review of Current Evidence of Neural Molecular Correlates and Perspectives on Drug Development.

Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been traditionally studied in embryonic development and oncology. Its dysregulation may impact brain homeostasis, neuroplasticity, and potential involvement in neural processes. This systematic review provides an overview of the involvement of Hh signalling in the pathophysiology of schizophrenia and antipsychotic responses. We searched the PubMed and Scopus databases to identify peer-reviewed scientific studies focusing on Hh and schizophrenia, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, finally including eight studies, including three articles focused on patients with schizophrenia, two animal models of schizophrenia, two animal embryo studies, and one cellular differentiation study. The Hh pathway is crucial in the development of midbrain dopaminergic neurons, neuroplasticity mechanisms, regulating astrocyte phenotype and function, brain-derived neurotrophic factor expression, brain glutamatergic neural transmission, and responses to antipsychotics. Overall, results indicate an involvement of Hh in the pathophysiology of schizophrenia and antipsychotic responses, although an exiguity of studies characterises the literature. The heterogeneity between animal and human studies is another main limitation. Further research can lead to better comprehension and the development of novel personalised drug treatments and therapeutic interventions.

Calls to the anti-violence number in Italy during COVID-19 pandemic: correlation and trend analyses of violence reports during 2020.

PURPOSE: We hypothesized that during the 2020 pandemic there has been a significant change along the year, depending on the SARS-CoV-2 impact on the population and varying difficulties implied in the norms that were adopted to embank the pandemic. Our objectives were to verify how the phenomenon of domestic violence has evolved and changed along 2020, and to clarify if these changes were correlated to the evolution of the pandemic. METHODS: Though the analysis of the number of daily calls from women to the national anti-violence number and the parameters related to COVID-19 pandemic (daily cases, deaths, hospitalizations, and admissions in ICU), a positive correlation was found between daily deaths due to COVID-19 and the number of calls to the anti-violence number, while daily hospitalizations and admissions in ICU negatively correlated with calls of women reporting at the national anti-violence number. RESULTS: The number of daily calls from women reporting at the national anti-violence number positively correlated with the number of quarantined people shifted of 30 days from the beginning of isolation at home, as well. We also analyzed temporal trends of daily calls from women to the national anti-violence number from 25th of February 2020 to 31st of December 2020. CONCLUSIONS: These findings demonstrate the importance of an active anti-violence telephone service and may help in developing a strategy to improve anti-violence facilities, especially during crises, such as specific sources of psychological support for women who have survived violence episodes.

A Systematic Review on Add-On Psychotherapy in Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders represent a varied class of mental illnesses characterised by psychosis. In addition to negative and positive symptoms, a significant lack of insight often hinders the therapeutic process. We performed an overview of the existing literature concerning these disorders to summarise the state of knowledge in the psychotherapies applied to treating psychotic symptoms. We searched the PubMed database, including randomised controlled and clinical trials, including 17 studies conducted on 1203 subjects. Psychotherapy of schizophrenia spectrum disorders can improve social functioning and positive symptoms, as well as many other symptomatic areas, and could therefore be considered a helpful adjunctive treatment of schizophrenia spectrum disorders. Among cognitive-behavioural therapies and the newest derived approaches, there is evidence that they can improve different psychotic symptoms. On the other hand, psychodynamic psychotherapies can have a positive influence on psychotic symptoms as well. Further studies are needed to identify better-tailored treatment protocols for schizophrenia spectrum disorders.

Facing the Shadow Pandemic: Correlation and Trend Analyses of Violence Reports from Women to the Italian National Anti-Violence Number during 2021.

OBJECTIVES: To help to tackle gender-based violence against women in the aftermath of COVID-19 or other potential crisis situations, as recommended by the European Institute for Gender Equality, the present study aims to investigate the relationship between calls to the National Anti-violence Number (NAN) and the socio-sanitary pandemic factors during 2021, a period in which the scenario changed due to containment measures that gradually allowed women to emerge from the condition of isolation. In addition, the present work aims to identify significant changes in the number of calls to NAN during the progression of the pandemic in 2021. METHODS: Using Italian Civil Protection Department data on the socio-sanitary pandemic factors (defined by daily number of cases, swabs, deaths, hospitalizations, dismissions, intensive care unit hospitalizations, people isolated at home, and quarantine after 15 and 30 days) and NAN data. Correlation analyses, a joinpoint regression analysis, and Granger causality tests were performed. RESULTS: The number of calls correlated with the daily number of cases, swabs, deaths, hospitalizations, dismissions, intensive care unit hospitalizations, and quarantine after 15 and 30 days. The identified joinpoints showed significant changes in the number of daily anti-violence calls during the year. Furthermore, we found evidence of a significant causality between daily hospitalizations, daily home quarantined, daily dismissed patients, and calls to NAN. CONCLUSIONS: The results underline the influence of containment measures on the increased access to NAN, suggesting the need for a greater implementation of social and psychological support services in other potential crisis situations.

Anxiety Symptoms, COVID-19-Related Stress Reactions in the Italian General Population, and Validation of the Italian COVID Stress Scales (CSS-I).

Background. The COVID Stress Scales (CSS) assess COVID-related stress experienced in the past week related to danger and contamination fears, socioeconomic consequences, xenophobia, compulsive checking, and reassurance seeking, and traumatic stress symptoms. Our objective was to provide a translation into Italian, replication, and psychometric validation of the CSS in the general population. Moreover, we aimed to test the convergent and discriminant validity of the Italian CSS (CSS-I) with respect to anxiety, stress, and depressive symptoms in the general Italian population. Method. Adult participants (n = 935) over the age of 18 years were recruited from the general population in Italy. Psychological status was assessed using multiple validated measures, including the CSS, Depression, Anxiety and Stress Scales-21 (DASS-21), and the Prejudice Against Immigrants Scale (PAIS). Results. Our confirmatory factor analysis supported a 6-factor model, including danger fears (DAN), socioeconomic consequences (SEC), xenophobia (XEN), compulsive checking and reassurance seeking (CHE), contamination fears (CON), and traumatic stress symptoms (TSS). Strong reliability of the CSS-I (Cronbach's α = 0.863-0.936) and convergent validity with the DASS-21 and PAI were established with positive correlations between total and scale scores across measures. Conclusions. The CSS-I is a valid and reliable instrument to measure COVID-19-related distress in the Italian population.

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

BACKGROUND: The objective of this study was to investigate the DRD2 rs1800497, rs1799732, rs1801028, DRD3 rs6280, and HTR2A rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders. METHODS: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership. RESULTS: A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the DRD3 rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, HTR2A rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and DRD2 rs1799732 I|I vs. D|I (OR = 12.079) genotypes. CONCLUSIONS: A diagnosis of schizophrenia and the DRD2 rs1799732, DRD3 rs6280, and HTR2A rs7997012 genotypes can predict high treatment resistance to SGAs.

Functional Neuroimaging in Dissociative Disorders: A Systematic Review.

BACKGROUND: Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders. METHODS: we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders. RESULTS: Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders. CONCLUSIONS: Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments.

Clinical Aspects of Manic Episodes After SARS-CoV-2 Contagion or COVID-19.

As COVID-19 pandemic spread all over the world, it brought serious health consequences in every medical field, including mental health. Not only healthcare professionals were more prone to develop anxiety, depression, and stress, but the general population suffered as well. Some of those who had no prior history of a psychiatric disease developed peculiar symptoms following infection with SARS-CoV-2, mostly because of psychological and social issues triggered by the pandemic. People developed traumatic memories, and hypochondria, probably triggered by social isolation and stress. Infection with SARS-CoV-2 has influenced the mental health of psychiatric patients as well, exacerbating prior psychiatric conditions. In this review, we focus on analyzing those cases of mania in the context of bipolar disorder (BD) reported after COVID-19 disease, both in people with no prior psychiatric history and in psychiatric patients who suffered an exacerbation of the disease. Results have shown that COVID-19 may trigger a pre-existing BD or unmask an unknown BD, due to social and psychological influences (decreased social interaction, change in sleep patterns) and through biological pathways both (neuroinflammation and neuroinvasion through ACE-2 receptors expressed in the peripheral and central nervous systems (PNS and CNS respectively). No direct correlation was found between the severity of COVID-19 disease and manic symptoms. All cases presenting severe symptoms of both diseases needed specific medical treatment, meaning that they concur but are separate in the treatment strategy needed. This review highlights the importance of a now widespread viral disease as a potential agent unmasking and exacerbating bipolar mood disorder, and it can hopefully help physicians in establishing a rapid diagnosis and treatment, and pave the road for future research on neuroinflammation triggered by SARS-CoV-2.

Neuroanatomical correlates of autism spectrum disorders: A meta-analysis of structural magnetic resonance imaging (MRI) studies.

Autism spectrum disorders (ASD) are neurodevelopmental disorders correlated to various neuroanatomical modifications. We aimed to identify neuroanatomical changes assessed in magnetic resonance imaging (MRI) studies of autism spectrum disorder (ASD) through Activation Likelihood Estimate (ALE) meta-analysis. We included 19 peer-reviewed magnetic resonance imaging (MRI) studies that analyzed cortical volume in patients with ASD compared to healthy control subjects (HCs). The between-group analyses comparing subjects with ASD to HCs showed a volumetric reduction of a large cluster in the right brain, including the uncus/amygdala, parahippocampal gyrus, and entorhinal cortex, and putamen. The anomalies are primarily found in the right hemisphere, involved in social cognitive function, particularly impaired in ASD. These results correlate with several clinical aspects of ASD. These volumetric alterations can be considered a major correlate of disease in the context of multifactorial etiology. Further studies on brain lateralization in ASD are needed, considering the clinical phenotype variability of these disorders.

Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders.

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders.

Correlations between cortical gyrification and schizophrenia symptoms with and without comorbid hostility symptoms.

Introduction: Interest in identifying the clinical implications of the neuropathophysiological background of schizophrenia is rising, including changes in cortical gyrification that may be due to neurodevelopmental abnormalities. Inpatients with schizophrenia can show abnormal gyrification of cortical regions correlated with the symptom severity. Methods: Our study included 36 patients that suffered an acute episode of schizophrenia and have undergone structural magnetic resonance imaging (MRI) to calculate the local gyrification index (LGI). Results: In the whole sample, the severity of symptoms significantly correlated with higher LGI in different cortical areas, including bilateral frontal, cingulate, parietal, temporal cortices, and right occipital cortex. Among these areas, patients with low hostility symptoms (LHS) compared to patients with high hostility symptoms (HHS) showed significantly lower LGI related to the severity of symptoms in bilateral frontal and temporal lobes. Discussion: The severity of psychopathology correlated with higher LGI in large portions of the cerebral cortex, possibly expressing abnormal neural development in schizophrenia. These findings could pave the way for further studies and future tailored diagnostic and therapeutic strategies.