Cardiovascular assessment of supportive doctor-patient communication using multi-scale and multi-lag analysis of heartbeat dynamics.

Emphatic doctor-patient communication has been associated with improved psycho-physiological well-being involving cardiovascular and neuroendocrine responses. Nevertheless, a comprehensive assessment of heartbeat linear and nonlinear dynamics throughout the communication of a life-threatening disease has not been performed yet. To this extent, we studied linear heartbeat dynamics through the extraction of time-frequency domain measurements, as well as heartbeat nonlinear and complex dynamics through novel approaches to compute multi-scale and multi-lag series analyses: namely, the multi-scale distribution entropy and lagged Poincaré plot symbolic analysis. Heart rate variability series were recorded from 54 healthy female subjects who were blind to the aim of the experiment. Participants were randomly assigned into two groups: 27 subjects watched a video where an oncologist discloses the diagnosis of a cancer metastasis to a patient, whereas the remaining 27 watched the same video including four additional supportive comments by the clinician. Considering differences between the beginning and the end of each communication video, results from non-parametric Wilcoxon tests demonstrated that, at a group level, significant differences occurred in heartbeat linear and nonlinear dynamics, with lower complexity during nonsupportive communication. Furthermore, a support vector machine algorithm, validated using a leave-one-subject-out procedure, was able to discern the supportive experience at a single-subject level with an accuracy of 83.33% when nonlinear features were considered, dropping to 51.85% when using standard HRV features only. In conclusion, heartbeat nonlinear and complex dynamics can be a viable tool for the psycho-physiological evaluation of supportive doctor-patient communication. Graphical Abstract Scheme of the three main stages of the study: signal acquisition during doctor-patient communication, ECG signal processing and pattern recognition results.

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.

Characterization of doctor-patient communication using heartbeat nonlinear dynamics: A preliminary study using Lagged Poincaré Plots.

Emphatic doctor-patient communication has been associated with an improved psycho-physiological well-being involving cardiovascular and neuroendocrine responses. Nevertheless, a comprehensive assessment of heartbeat linear and nonlinear/complex dynamics throughout the communication of a life-threatening disease has not been performed yet. To this extent, we here study heart rate variability (HRV) series gathered from 17 subjects while watching a video where an oncologist discloses the diagnosis of a cancer metastasis to a patient. Further 17 subjects watched the same video including additional affective emphatic contents. For the assessment of the two groups, linear heartbeat dynamics was quantified through measures defined in the time and frequency domains, whereas nonlinear/complex dynamics referred to measures of entropy, and combined Lagged Poincare Plots (LPP) and symbolic analyses. Considering differences between the beginning and the end of the video, results from non-parametric statistical tests demonstrated that the group watching emphatic contents showed HRV changes in the LF/HF ratio exclusively. Conversely, the group watching the purely informative video showed changes in vagal activity (i.e., HF power), LF/HF ratio, as well as LPP measures. Additionally, a Support Vector Machine algorithm including HRV nonlinear/complex information was able to automatically discern between groups with an accuracy of 76.47%. We therefore propose the use of heartbeat nonlinear/complex dynamics to objectively assess the empathy level of healthy women.

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.

Neuropsychological underpinnings of the dynamics of bipolar disorder.

Although we have gained enormous insights into neurobiological and psychological underpinnings of bipolar disorder (BD) symptoms, our knowledge concerning pathogenic mechanisms initiating recurrent affective episodes is still fragmentary. Previous research has highlighted the role of significant life events and social rhythm in recurrent episodes of mania and depression. However, most studies share the drawback of retrospective self-report data, which are prone to recall biases and limited introspective abilities. Therefore, more objective data, such as neuropsychological and neurobiological measures are needed to further unravel the pathogenic mechanisms of the dynamics of bipolar disorder. Previous research has highlighted disturbed emotional reactivity as well as impaired emotion regulation and impulse control as major behavioural characteristics of BD and aberrancies in prefrontal-limbic-striatal networks that have been proposed to be the correlates of these behavioural alterations. However, longitudinal studies assessing these neural and behavioural alterations are rare. Future research should therefore adopt prospective study designs including behavioural and neuroimaging measures underlying cognitive, emotional and motivational deficits in bipolar disorder. Particularly, these measures should be collected continuously at multiple time points as implemented in modern ambulatory assessment tools.

Applying neuroimaging to detect neuroanatomical dysconnectivity in psychosis.

This editorial discusses the application of a novel brain imaging analysis technique in the assessment of neuroanatomical dysconnectivity in psychotic illnesses. There has long been a clinical interest in psychosis as a disconnection syndrome. In recent years graph theory metrics have been applied to functional and structural imaging datasets to derive measures of brain connectivity, which represent the efficiency of brain networks. These metrics can be derived from structural neuroimaging datasets acquired using diffusion imaging whereby cortical structures are parcellated into nodes and white matter tracts represent edges connecting these nodes. Furthermore neuroanatomical measures of connectivity may be decoupled from measures of physiological connectivity as assessed using functional imaging, underpinning the need for multi-modal imaging approaches to probe brain networks. Studies to date have reported a number of structural brain connectivity abnormalities associated with schizophrenia that carry potential as illness biomarkers. Structural connectivity abnormalities have also been reported in well patients with bipolar disorder and in unaffected relatives of patients with schizophrenia. Such connectivity metrics may represent clinically relevant biomarkers in studies employing a longitudinal design of illness course in psychosis.

Epidemiological and clinical aspects will guide the neuroimaging research in bipolar disorder.

Although neurobiological mechanisms of bipolar disorder (BD) are still unclear, neural models of the disease have recently been conceptualised thanks to neuroimaging. Indeed, magnetic resonance imaging (MRI) studies investigating structural and functional connectivity between different areas of the brain suggest an altered prefrontal-limbic coupling leading to disrupted emotional processing in BD, including uncinate fasciculus, amygdala, parahippocampal cortex, cingulate cortex as well corpus callosum. Specifically, these models assume an altered prefrontal control over a hyperactivity of the subcortical limbic structures implicated in automatic emotional processing. This impaired mechanism may finally trigger emotional hyper-reactivity and mood episodes. In this review, we first summarised some key neuroimaging studies on BD. In the second part of the work, we focused on the heterogeneity of the available studies. This variability is partly due to methodological factors (i.e., small sample size) and differences among studies (i.e., MRI acquisition and post-processing analyses) and partly to the clinical heterogeneity of BD. We finally outlined how epidemiological studies should indicate which risk factors and clinical dimensions of BD are relevant to be studied with neuroimaging in order to reduce heterogeneity and go beyond diagnostic categories.

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.

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.

Psychosis Incident Cohort Outcome Study (PICOS). A multisite study of clinical, social and biological characteristics, patterns of care and predictors of outcome in first-episode psychosis. Background, methodology and overview of the patient sample.

AIMS: This paper aims at providing an overview of the background, design and initial findings of Psychosis Incident Cohort Outcome Study (PICOS). METHODS: PICOS is a large multi-site population-based study on first-episode psychosis (FEP) patients attending public mental health services in the Veneto region (Italy) over a 3-year period. PICOS has a naturalistic longitudinal design and it includes three different modules addressing, respectively, clinical and social variables, genetics and brain imaging. Its primary aims are to characterize FEP patients in terms of clinical, psychological and social presentation, and to investigate the relative weight of clinical, environmental and biological factors (i.e. genetics and brain structure/functioning) in predicting the outcome of FEP. RESULTS: An in-depth description of the research methodology is given first. Details on recruitment phase and baseline and follow-up evaluations are then provided. Initial findings relating to patients' baseline assessments are also presented. Future planned analyses are outlined. CONCLUSIONS: Both strengths and limitations of PICOS are discussed in the light of issues not addressed in the current literature on FEP. This study aims at making a substantial contribution to research on FEP patients. It is hoped that the research strategies adopted in PICOS will enhance the convergence of methodologies in ongoing and future studies on FEP.

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.

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.

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.

Language disturbances in ADHD.

This article aims to review the studies exploring language abilities in attention deficit hyperactivity disorder (ADHD; with or without comorbid language impairment) focusing on oral speech discrimination, listening comprehension, verbal and spatial working memory as well as on discourse analysis and pragmatic aspects of communication and language comprehension.

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.

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.

Cortical white-matter microstructure in schizophrenia. Diffusion imaging study.

BACKGROUND: Several, although not all, of the previous small diffusion-weighted imaging (DWI) studies have shown cortical white-matter disruption in schizophrenia. AIMS: To investigate cortical white-matter microstructure with DWI in a large community-based sample of people with schizophrenia. METHOD: Sixty-eight people with schizophrenia and 64 healthy controls underwent a session of DWI to obtain the apparent diffusion coefficient (ADC) of white-matter water molecules. Regions of interest were placed in cortical lobes. RESULTS: Compared with controls, the schizophrenia group had significantly greater ADCs in frontal, temporal and occipital white matter (analysis of covariance, P < 0.05). CONCLUSIONS: Our findings confirm the presence of cortical white-matter microstructure disruption in frontal and temporo-occipital lobes in the largest sample of people with schizophrenia thus for studied with this technique. Future brain imaging studies, together with genetic investigations, should further explore white-matter integrity and genes encoding myelin-related protein expression in people with first-episode schizophrenia and those at high risk of developing the disorder.

Is the birthdate a risk factor for congenital hypothyroidism? A statistical answer based on personal experience.

BACKGROUND: To verify statistically the hypothesis that birthdate represents a risk factor for Congenital Hypothyroidism, as proposed by some European Authors. Moreover, to verify the existence of seasonal cyclic trends in TSH levels. METHODS: For the verification of birthdate as a risk factor, we considered retrospectively a data set of all consecutives newborns of Marche Region (Italy) affected by Congenital Hypothyroidism, in the period 1981-1996 (n = 92). For the evaluation of seasonal cyclic trends in TSH, we considered the level of the hormone in all newborns of Marche Region screened in the period 1989-1996. Data were collected from Neonatal Screening Register of Marche Region. All the statistical analyses are based on circular statistics techniques (Rayleigh test, Roger test, estimation of density by kernel method, Mardia test for circular-linear correlation, Maximization of Mean Vector Length). RESULTS: No cyclic trend was pointed out with regard to Congenital Hypothyroidism; neither seasonal rhythms nor other cyclic patterns of TSH levels were evidenced. CONCLUSIONS: Neither the hypothesis of birthdate as a risk factor for Congenital Hypothyroi-dism, nor the existence of seasonal variations in TSH hormone releasing were confirmed.