Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study.

BACKGROUND: Hippocampal shrinkage is commonly reported in schizophrenia, but its role in the illness is still poorly understood. In particular, it is unclear how clinical and psychosocial variables relate to hippocampal volumes. AIMS: To investigate neuroanatomic differences in the hippocampus using three-dimensional (3D) computational image analysis. METHOD: We used high-resolution magnetic resonance imaging and surface-based modelling to map the 3D profile of hippocampal differences in adults with schizophrenia (n = 67) and a healthy control group (n = 72). Manual tracings were used to create 3D parametric mesh models of the hippocampus. Regression models were used to relate diagnostic measures to maps of radial distance, and colour-coded maps were generated to show the profile of associations. RESULTS: There was no detectable difference between the schizophrenia and control groups in hippocampal radial distance. In the schizophrenia group, however, bilateral shape deflation was associated with greater illness severity (length of illness, positive and negative symptoms) and with poorer social functioning (educational level, quality of life and health status), which survived Bonferroni correction. CONCLUSIONS: Illness severity and poor social functioning may be associated with hippocampal deflation in schizophrenia. As a structural sign of poor outcome, imaging measures might help to identify a subgroup of patients who may need specific treatment to resist hippocampal shrinkage, such as cognitive rehabilitation or physical exercise.

Increased salience of gains versus decreased associative learning differentiate bipolar disorder from schizophrenia during incentive decision making.

BACKGROUND: Abnormalities in incentive decision making, typically assessed using the Iowa Gambling Task (IGT), have been reported in both schizophrenia (SZ) and bipolar disorder (BD). We applied the Expectancy-Valence (E-V) model to determine whether motivational, cognitive and response selection component processes of IGT performance are differentially affected in SZ and BD. METHOD: Performance on the IGT was assessed in 280 individuals comprising 70 remitted patients with SZ, 70 remitted patients with BD and 140 age-, sex- and IQ-matched healthy individuals. Based on the E-V model, we extracted three parameters, 'attention to gains or loses', 'expectancy learning' and 'response consistency', that respectively reflect motivational, cognitive and response selection influences on IGT performance. RESULTS: Both patient groups underperformed in the IGT compared to healthy individuals. However, the source of these deficits was diagnosis specific. Associative learning underlying the representation of expectancies was disrupted in SZ whereas BD was associated with increased incentive salience of gains. These findings were not attributable to non-specific effects of sex, IQ, psychopathology or medication. CONCLUSIONS: Our results point to dissociable processes underlying abnormal incentive decision making in BD and SZ that could potentially be mapped to different neural circuits.

Classification of schizophrenia using feature-based morphometry.

The objective of this study was to use a combined local descriptor, namely scale invariance feature transform (SIFT), and a non linear support vector machine (SVM) technique to automatically classify patients with schizophrenia. The dorsolateral prefrontal cortex (DLPFC), considered a reliable neuroanatomical marker of the disease, was chosen as region of interest (ROI). Fifty-four schizophrenia patients and 54 age- and gender-matched normal controls were studied with a 1.5T MRI (slice thickness 1.25 mm). Three steps were conducted: (1) landmark detection and description of the DLPFC, (2) feature vocabulary construction and Bag-of-Words (BoW) computation for brain representation, (3) SVM classification which adopted the local kernel to implicitly implement the feature matching. Moreover, a new weighting approach was proposed to take into account the discriminant relevance of the detected groups of features. Substantial results were obtained for the classification of the whole dataset (left side 75%, right side 66.38%). The performances were higher when females (left side 84.09%, right side 77.27%) and seniors (left side 81.25%, right side 70.83%) were considered separately. In general, the supervised weighed functions increased the efficacy in all the analyses. No effects of age, gender, antipsychotic treatment and chronicity were shown on DLPFC volumes. This integrated innovative ROI-SVM approach allows to reliably detect subjects with schizophrenia, based on a structural brain marker for the disease such as the DLPFC. Such classification should be performed in first-episode patients in future studies, by considering males and females separately.

Structural imaging techniques in schizophrenia.

OBJECTIVE: The aim of this overview study is to translate the technical terminology regarding structural Magnetic Resonance Imaging (sMRI) post-processing analysis into a clinical clear description. METHOD: We resumed and explained the most popular post-processing methods for structural MRI (sMRI) data applied in psychiatry and their main contributions to the comprehension of the biological basis of schizophrenia. RESULTS: The region-of-interest (ROI) technique allows to investigate specific brain region size by manual tracing; it is anatomically precise and requires a priori hypothesis, but also it is time-consuming and operator-dependent. The voxel-based morphometry (VBM) detects gray matter density across the whole brain by comparing voxel to voxel; it is operator-independent, does not require a priori hypothesis, and is relatively fast; however, it is limited by multiple comparisons and poor anatomical definition. Finally, computational neuroanatomical analyses have recently been applied to automatically discriminate subjects with schizophrenia from healthy subjects on the basis of MRI images. CONCLUSION: Structural MRI represents a useful tool in understanding the biological underpinnings of schizophrenia and in planning focused interventions, thus assisting clinicians especially in the early phases of the illness.

Linguistic production and syntactic comprehension in schizophrenia and bipolar disorder.

OBJECTIVE: To explore linguistic abilities in schizophrenia and bipolar disorder. Specifically, the aims of this study were to: i) investigate microlinguistic (lexicon, morphology, syntax) and macrolinguistic (discourse coherence, pragmatics) dimensions of speech production and ii) evaluate syntactic comprehension skills in both schizophrenia and bipolar disorder. METHOD: Linguistic performance of 30 Italian-speaking patients with schizophrenia, 30 participants with bipolar disorder and 30 healthy controls comparable for age and educational level has been assessed using a story-telling task and a computer-based test of syntactic comprehension. RESULTS: In narrative production, compared with healthy participants, those with schizophrenia had slight problems in speech rate and deficits at both local and global discourse coherence, whereas patients with bipolar disorder showed reduced mean length of utterance. As regards syntactic comprehension, both groups of patients collected more grammatical errors than controls, but they differed with regard to the number and kind of grammatical construction they missed. CONCLUSION: Linguistic deficits have been detected in both groups of patients, being, however, more severe and generalized in schizophrenia than in bipolar disorder. Such results help us in improving our understanding of the potential psychopathological overlapping between these disorders.

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.

Altered microstructure integrity of the amygdala in schizophrenia: a bimodal MRI and DWI study.

BACKGROUND: The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes. METHOD: In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures. RESULTS: Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia. CONCLUSIONS: We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.

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.

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.

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.

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.

Increased fronto-temporal perfusion in bipolar disorder.

OBJECTIVES: Previous imaging reports showed over-activation of fronto-limbic structures in bipolar patients, particularly in response to emotional stimuli. In this study, for the first time, we used perfusion weighted imaging (PWI) to analyze lobar cerebral blood volume (CBV) in bipolar disorder to further explore the vascular component to its pathophysiology. METHODS: Fourteen patients with DSM-IV bipolar disorder (mean age+/-SD=49.00+/-12.30 years; 6 males, 8 females) and 29 normal controls (mean age+/-SD=45.07+/-10.30 years; 13 males, 16 females) were studied. PWI images were obtained following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), with a 1.5 T Siemens magnet using an echo-planar sequence. The contrast of enhancement (CE), was calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/So*100) for frontal, temporal, parietal, and occipital lobes, bilaterally, on two axial images. Higher CE values correspond to lower CBV and viceversa. RESULTS: Bipolar patients had significantly lower CE values in left frontal and temporal lobes (p=0.01 and p=0.03, respectively) and significantly inverse laterality index for frontal lobe (p=0.017) compared to normal controls. No significant correlations between CE measure and age or clinical variables were found (p>0.05). CONCLUSION: This study found increased left frontal and temporal CBV in bipolar disorder. Fronto-temporal hyper-perfusion may sustain over-activation of these structures during emotion modulation, which have been observed in patients with bipolar illness.

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.

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.

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.