Preclinical and clinical evidence on the approach-avoidance conflict evaluation as an integrative tool for psychopathology.

The approach-avoidance conflict (AAC), i.e. the competing tendencies to undertake goal-directed actions or to withdraw from everyday life challenges, stands at the basis of humans' existence defining behavioural and personality domains. Gray's Reinforcement Sensitivity Theory posits that a stable bias toward approach or avoidance represents a psychopathological trait associated with excessive sensitivity to reward or punishment. Optogenetic studies in rodents and imaging studies in humans associated with cross-species AAC paradigms granted new emphasis to the hippocampus as a hub of behavioural inhibition. For instance, recent functional neuroimaging studies show that functional brain activity in the human hippocampus correlates with threat perception and seems to underlie passive avoidance. Therefore, our commentary aims to (i) discuss the inhibitory role of the hippocampus in approach-related behaviours and (ii) promote the integration of functional neuroimaging with cross-species AAC paradigms as a means of diagnostic, therapeutic, follow up and prognosis refinement in psychiatric populations.

Position paper of the Italian Association of Medical Oncology on the impact of COVID-19 on Italian oncology and the path forward: the 2021 Matera statement.

The coronavirus disease 2019 (COVID-19) pandemic has severely affected cancer care and research by disrupting the prevention and treatment paths as well as the preclinical, clinical, and translational research ecosystem. In Italy, this has been particularly significant given the severity of the pandemic's impact and the intrinsic vulnerabilities of the national health system. However, whilst detrimental, disruption can also be constructive and may stimulate innovation and progress. The Italian Association of Medical Oncology (AIOM) has recognized the impact of COVID-19 on cancer care continuum and research and proposes the '2021 Matera statement' which aims at providing pragmatic guidance for policymakers and health care institutions to mitigate the impact of the global health crisis on Italian oncology and design the recovery plan for the post-pandemic scenario. The interventions are addressed both to the pillars (prevention, diagnosis, treatment, follow-up, health care professionals) and foundations of cancer care (communication and care relationship, system organization, resources, research, networking). The priorities to be implemented can be summarized in the MATERA acronym: Multidisciplinarity; Access to cancer care; Telemedicine and Territoriality; Equity, ethics, education; Research and resources; Alliance between stakeholders and patients.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Olfactory and gustatory dysfunctions in SARS-CoV-2 infection: A systematic review.

BACKGROUND: Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: A systematic review comprising all the observational studies that reported the prevalence and/or the longitudinal trajectories of OGD in COVID-19 patients, as self-reported by patients or measured through objective psychophysical tests. RESULTS: After the selection process, 155 studies were included, with a total of 70,920 patients and 105,291 not-infected individuals. Prevalence reports were extremely variable across studies, with wide ranges for OD (0%-98%) and GD (0-89%) prevalence. OGD occurred early during the disease course and only rarely preceded other symptoms; out of 30 studies with a follow-up time of at least 20 days, only in 5 studies OGD fully resolved in more than 90% of patients. OGD had low sensitivity and high specificity for SARS-CoV-2 infection; accuracy of OD and GD for infection identification was higher than 80% in 10 out of 33 studies and in 8 out of 22 studies considered, respectively. 28 out of 30 studies that studied the association between OGD and disease severity found how OGD were associated with lower rates of severe pneumonia, hospitalization and mortality. CONCLUSIONS: OGD seem to be highly prevalent in SARS-CoV-2 infection. They occur early, concomitantly with other symptoms and often persist after recovery, in some cases for months; whether a full recovery eventually occurs in all cases is not clear yet. OGD are good predictors of SARS-CoV-2 infection and are associated with a milder disease course.

Automated cortical thickness and skewness feature selection in bipolar disorder using a semi-supervised learning method.

BACKGROUND: Bipolar disorder (BD) broadly affects brain structure, in particular areas involved in emotion processing and cognition. In the last years, the psychiatric field's interest in machine learning approaches has been steadily growing, thanks to the potentiality of automatically discriminating patients from healthy controls. METHODS: In this work, we employed cortical thickness of 58 regions of interest obtained from magnetic resonance imaging scans of 41 BD patients and 34 healthy controls, to automatically identify the regions which are mostly involved with the disease. We used a semi-supervised method, addressing the criticisms on supervised methods, related to the fact that the diagnosis is not unaffected by uncertainty. RESULTS: Our results confirm findings in previous studies, with a classification accuracy of about 75% when mean thickness and skewness of up to five regions are considered. We obtained that the parietal lobe and some areas in the temporal sulcus were the regions which were the most involved with BD. LIMITATIONS: The major limitation of our work is the limited size or our dataset, but in line with other recent machine learning works in the field. Moreover, we considered chronic patients, whose brain characteristics may thus be affected. CONCLUSIONS: The automatic selection of the brain regions most involved in BD may be of great importance when dealing with the pathogenesis of the disorder. Our method selected regions which are known to be involved with BD, indicating that damage to the identified areas can be considered as a marker of disease.

MRI features of clinical outcome in bipolar disorder: A selected review: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Bipolar disorder (BD) is a severe and disabling mental illness, which is characterized by selective gray matter (GM) and white matter (WM) brain alterations, as observed by several imaging studies. However, the clinical course of the disease is uncertain and can vary across BD patients, with some having a benign course and others a severe disability. In this perspective, magnetic resonance imaging (MRI) can help identifying biological markers of worse prognosis. METHODS: The present selected review aimed at summarizing structural MRI (sMRI) studies exploring the correlation between brain morphology and features of clinical outcome, which could include treatment response, cognitive impairment and global functioning. RESULTS: Overall, the results from the reviewed sMRI studies reported that WM hyperintensities and GM volume reductions, mainly in fronto-limbic areas, correlate with worse outcome in BD. However, the selected outcome measures vary across studies, thus these observations cannot be conclusive. LIMITATIONS: Heterogeneity across studies and inconsistency on the outcome measures adopted limit the conclusion of the present review. Absence of widely shared definitions of outcome should be object of further research on BD in order to indicate more stable features of illness course. CONCLUSIONS: In summary, WM hyperintensities and fronto-temporo-limbic GM alterations may be potential indices of worse outcome in BD patients, particularly in terms of illness severity and progression. The identification of stable markers of prognosis can help the clinicians in selecting subgroups of bipolar patients who need specific treatment to preserve cognitive / psychosocial functioning, in the light of personalized approaches. To further characterize outcome in BD, future sMRI studies should a) longitudinally investigate patients with either poor or good course of the disease, and b) correlate neuroimaging measures with clinical, cognitive and genetic markers.

The neural basis of hostility-related dimensions in schizophrenia.

Hostility and related dimensions like anger, urgency, impulsivity and aggressiveness have been described in non-clinical populations and various serious mental illnesses including schizophrenia. Although representing a mental healthcare challenge, the investigation of such constructs is often limited by the presence of complex and multi-factorial causes and lack of agreement in their conceptualisation and measurement. In this review, we aim to clarify the anatomical basis of hostility-related dimensions in schizophrenia. Imaging studies suggest malfunctioning of a neural circuitry including amygdala, striatum, prefrontal cortex, anterior cingulate cortex, insula and hippocampus to modulate hostile thoughts and behaviours, at least in the subgroup of patients with schizophrenia who exhibit high levels of urgency, impulsivity and aggressiveness.

A review of altered biochemistry in the anterior cingulate cortex of first-episode psychosis.

Relevant biochemicals of the brain can be quantified in vivo, non-invasively, using proton Magnetic Resonance Spectroscopy (¹H MRS). This includes metabolites associated with neural general functioning, energetics, membrane phospholipid metabolism and neurotransmission. Moreover, there is substantial evidence of implication of the frontal and prefrontal areas in the pathogenesis of psychotic disorders such as schizophrenia. In particular, the anterior cingulate cortex (ACC) plays an important role in cognitive control of emotional and non-emotional processes. Thus the study of its extent of biochemistry dysfunction in the early stages of psychosis is of particular interest in gaining a greater understanding of its aetiology. In this review, we selected ¹H MRS studies focused on the ACC of first-episode psychosis (FEP). Four studies reported increased glutamatergic levels in FEP, while other four showed preserved concentrations. Moreover, findings on FEP do not fully mirror those in chronic patients. Due to conflicting findings, larger longitudinal ¹H MRS studies are expected to further explore glutamatergic neurotransmission in ACC of FEP in order to have a better understanding of the glutamatergic mechanisms underlying psychosis, possibly using ultra high field MR scanners.

Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: A 3-year longitudinal study.

INTRODUCTION: Schizophrenia is a severe disabling disorder with heterogeneous illness courses. In this longitudinal study we characterized schizophrenia patients with poor and good outcome (POS, GOS), using functional and imaging metrics. Patients were defined in accordance to Keefe's criteria (i.e. Kraepelinian and non-Kraepelinian patients). METHODS: 35 POS patients, 35 GOS patients and 76 healthy controls (H) underwent clinical, functioning and magnetic resonance imaging (MRI) assessments twice over three years of follow-up. Information on psychopathology, treatment, disability (using the World Health Organization Disability Assessment Scale II, WHO-DAS-2) and prefrontal morphology was collected. Dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) were manually traced. RESULTS: At baseline, subjects with POS showed significantly decreased right dorsolateral prefrontal cortex (DLPFC) white matter volumes (WM) compared to healthy controls and GOS patients (POS VS HC, p<0.001; POS vs GOS, p=0.03), with shrinkage of left DLPFC WM volumes at follow up (t=2.66, p=0.01). Also, POS patients had higher disability in respect to GOS subjects both at baseline and after 3years at the WHO-DAS-2 (p<0.05). DISCUSSION: Our study supports the hypothesis that POS is characterized by progressive deficits in brain structure and in "real-life" functioning. These are particularly notable in the DLPFC.

Twin studies for the investigation of the relationships between genetic factors and brain abnormalities in bipolar disorder.

The pathogenesis of bipolar disorder (BD) is to date not entirely clear. Classical genetic research showed that there is a contribution of genetic factors in BD, with high heritability. Twin studies, thanks to the fact that confounding factors as genetic background or family environment are shared, allow etiological inferences. In this work, we selected twin studies, which focus on the relationship between BD, genetic factors and brain structure, evaluated with magnetic resonance imaging. All the studies found differences in brain structure between BD patients and their co-twins, and also in respect to healthy controls. Genetic effects are predominant in white matter, except corpus callosum, while gray matter resulted more influenced by environment, or by the disease itself. All studies found no interactions between BD and shared environment between twins. Twin studies have been demonstrated to be useful in exploring BD pathogenesis and could be extremely effective at discriminating the neural mechanisms underlying BD.

Neuroanatomical voxel-based profile of schizophrenia and bipolar disorder.

Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology (Ellison-Wright and Bullmore, 2009), the neural mechanisms underlying these disorders are still under investigation. Up until now, many neuroimaging studies investigated the brain structural differences of SCZ and BD compared with healthy controls (HC), trying to identify the possible neuroanatomical markers for the two disorders. However, just a few studies focused on the brain structural changes between the two diagnoses. The present review summarises the findings of the voxel-based grey matter (GM) comparisons between SCZ and BD, with the objective to highlight the possible consistent anatomical differences between the two disorders. While the comparisons between patients and HC highlighted overlapping areas of GM reduction in insula and anterior cingulate cortex, the SCZ-BD comparisons suggest the presence of more generalised GM deficits in SCZ compared with BD. Indeed, in a number of studies, SCZ patients showed lower GM volumes than BD patients in fronto-temporal cortex, thalamus, hippocampus and amygdala. Conversely, only a couple of studies reported GM deficits in BD compared with SCZ, both at the level of cerebellum. In summary, the two disorders exhibit both common and specific neuroanatomical characteristics, whose knowledge is mandatory to develop innovative diagnostic and treatment strategies.

The association between the serotonin and dopamine neurotransmitters and personality traits.

Evidence from previous studies has reported that complex traits, including psychiatric disorders, are moderately to highly heritable. Moreover, it has also been shown that specific personality traits may increase the risk to develop mental illnesses. Therefore the focus of the research shifted towards the identification of the biological mechanisms underpinning these traits by exploring the effects of a constellation of genetic polymorphisms in healthy subjects. Indeed, studying the effect of genetic variants in normal personality provides a unique means for identifying candidate genes which may increase the risk for psychiatric disorders. In this review, we discuss the impact of two of the most frequently studied genetic polymorphisms on personality in healthy subjects, the 5-HTT polymorphism of the serotonin transporter and the DRD2/DRD4 polymorphisms of the D2/D4 dopamine's receptors. The main aims are: (a) to highlight that the study of candidate genes provides a fruitful ground for the identification of the biological underpinnings of personality without, though, reaching a general consensus about the strength of this relationship; and (b) to outline that the research in personality genetics should be expanded to provide a clearer picture of the heritability of personality traits.

Basal ganglia anatomy and schizophrenia: the role of antipsychotic treatment.

Progressive enlargement of basal ganglia volume has been observed in schizophrenia individuals, potentially being sustained by chronic administration of antipsychotic drugs. Here we briefly summarise the state of the art of the role of antipsychotic in leading to increased basal ganglia in schizophrenia, particularly focusing on the caudate nucleus.

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia.

We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfß (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives.

This editorial offers a concise overview of the recent structural magnetic resonance imaging studies that evaluate the basal ganglia (BG) volumes in autism spectrum disorders (ASD). The putative relationship between the repetitive or stereotyped behaviours of ASD and BG volumes is also explored, with a focus on possible translational approaches.

Discordant twins as a tool to unravel the aetiology of bipolar disorder.

This editorial focuses on discordant twins as a valuable epidemiological design for psychiatric aetiological research. First, we summarise the advantages and strengths of this design over the classical matched case-control study. Then, we draw attention to the use of this method in bipolar disorder, revising previous discordant-twin studies. A future greater use of discordant twins is desirable to gain further relevant insights in the aetiology of bipolar disorder.

Cognitive remediation in schizophrenia: background, techniques, evidence of efficacy and perspectives.

Impairment of cognitive functions is a core feature of schizophrenia with relevant consequences on patients' psychosocial functioning. Cognitive remediation techniques have been recently developed with the aim to restore or compensate for such impairments and improve the functional outcome of the disease. There is now convincing evidence of the efficacy of many of these techniques, especially when delivered in the context of a comprehensive treatment programme. Whether the application of these techniques in the early phases of the disease could modify the disease course and outcome and how they could affect brain plasticity and the trajectory of brain disease of schizophrenia is still under scrutiny.

Brain anatomy of autism spectrum disorders II. Focus on amygdala.

This brief review encompasses the key findings of structural Magnetic Resonance Imaging (sMRI) research on amygdala volume in autism spectrum disorders (ASD). We also highlight the possible correlation between the autistic behavioural phenotype and amygdala alteration.

Brain anatomy of autism spectrum disorders I. Focus on corpus callosum.

This brief review aims to examine the structural magnetic resonance imaging (sMRI) studies on corpus callosum in autism spectrum disorders (ASD) and discuss the clinical and demographic factors involved in the interpretation of results.