Neural functional correlates of emotional processing in patients with first-episode psychoses: an activation likelihood estimation (ALE) meta-analysis.

BACKGROUND: Early emotional recognition impairment characterises rst-episode psychoses (FEP) and remains stable thereafter. Patients with FEP consistently show brain activation changes during emotional processing in functional neuroimaging studies. AIM AND METHODS: To identify and compare cerebral activation correlates of FEP patients and healthy controls (HCs) during emotional task performances, we performed an Activation Likelihood Estimation (ALE) meta-analysis of peer-reviewed functional magnetic resonance imaging (fMRI) studies. RESULTS: Five studies included 71 patients with FEP and 75 HCs. Within-group analyses showed that HCs activated during emotional task performance the bilateral inferior parietal lobule (BAs 39 and 40), left inferior frontal gyrus (BAs 9 and 47), right amygdala, left middle frontal gyrus (BA 9), right cingulate gyrus (BA 32), and right middle temporal gyrus (BA 21). FEP activations correlating with emotional tasks included the right cuneus (BA 17) and right angular gyrus (BA 39). CONCLUSIONS: During emotional task performance, FEP patients fail to activate an extensive brain network comprising emotional processing-related areas, including both cortical and subcortical areas.

Comparison of psychotic bipolar disorder, schizoaffective disorder, and schizophrenia: an international, multisite study.

OBJECTIVE: Nosological distinctions among schizoaffective disorder (SA), bipolar I disorder with psychotic features (BDp), and schizophrenia (SZ) remain unresolved. METHOD: We compared 2269 subjects with psychotic features in DSM-IV-TR diagnoses (1435 BDp, 463 SZ, 371 SA) from 8 collaborating international sites, by 12 sociodemographic and clinical measures, all between diagnostic pairs. RESULTS: In bivariate comparisons, SA was consistently intermediate between BDp and SZ for 11/12 features (except onset stressors), and SZ vs. BDp differed in all 12 factors. SA differed from both BDp and SZ in 9/12 factors: SA and BDp were similar in education and suicidal ideation or acts; SA and SZ were similar in education, onset stressors, and substance abuse. Meta-analytic comparisons of diagnostic pairs for 10 categorical factors indicated similar differences of SA from both SZ and BDp. Multivariate modeling indicated significantly independent differences between BDp and SZ (8 factors), SA vs. SZ (5), and BDp vs. SA (3). Measurement variance was similar for all diagnoses. CONCLUSION: SA was consistently intermediate between BDp and SZ. The three diagnostic groups ranked: BDp > SA > SZ related to lesser morbidity or disability. The findings are not consistent with a dyadic Kraepelinian categorization, although the considerable overlap among the three DSM-IV diagnostic groups indicates uncertain boundaries if they represent distinct disorders.

Weighing the stigma of weight: An fMRI study of neural reactivity to the pain of obese individuals.

Explicit negative attitudes and blameful beliefs (e.g. poor diet, laziness) towards obese individuals are well documented and are pervasive even among health professionals. Here we sought to determine whether obesity stigma is reflected in a fundamental feature of intersubjectivity namely the automatic neural resonance with others' affective experiences. During fMRI, normal-weight female participants observed short clips depicting normal-weight (NW) and obese (Ob) models experiencing pain. Importantly, participants believed that half of the Ob were overweight due to a hormonal disorder (HormOb) and ignored the cause of obesity of the remaining models (Unknown obese models; UnkOb). Analyses of hemodynamic responses showed reduced activity to the pain of Ob compared to that of NW in areas associated with pain processing and early visual processing. The comparison between the two Ob conditions revealed a further decrease of activity to HormOb's pain compared to UnkOb's (and NW) pain in the right inferior frontal gyrus, an area associated with emotional resonance. Our study demonstrates that stigma for obese individuals can be observed at implicit levels, and that it is modulated by knowledge concerning the etiology of obesity, with the seemingly surprising result that obesity due to disease may result in greater stigmatization. Moreover, the perceived similarity with the models and the ambivalent emotion of pity may index biased brain responses to obese individuals' pain. The study highlights a possibly important neural link between resonance with the pain of others and obesity stigma.

DSM-5 criteria for depression with mixed features: a farewell to mixed depression.

OBJECTIVE: To review the DSM-5 proposed criteria for mixed depression in light of robust and consistent historical and scientific evidence. METHOD: An extensive historical search, a systematic review of the papers used by DSM-5 as reference papers, and a PubMed search were performed. RESULTS: As Hippocrates, depressive mixed states have been described as conditions of intense psychic suffering, consisting of depressed mood, inner tension, restlessness, and aimless psychomotor agitation. In DSM-5, new criteria are proposed for a mixed features specifier, as part of depression either in major depressive disorder (MDD) or bipolar disorder. Those criteria require, as diagnostically specific, manic/hypomanic symptoms that are the least common kinds of symptoms that actually arise in depressive mixed states. The DSM-5 proposal is based, almost entirely, on a speculative wish to avoid 'overlapping' manic and depressive symptoms. Mixed states are, in fact, nothing but overlapping manic and depressive symptoms. CONCLUSION: In this article, we review the psychopathology and research on mixed depressive states, and try to demonstrate that the DSM-5 proposal has weak scientific basis and does not identify a large number of mixed depressive states. This may be harmful because of the different treatment required by these conditions.

Beneficial effects of a program of Mindfulness by remote during COVID-19 lockdown.

OBJECTIVE: In the emergency context of COVID-19 pandemic and lockdown, mindfulness relaxation techniques can provide a safe and effective strategy to obtain in a reasonably short time some degree of relief from suffering and to guarantee a greater confidence with emotional reactions in the general population. SUBJECTS AND METHODS: The Mindfulness-Based Stress Reduction program for coping with COVID-19 emergency was designed as an 8-week program during the early phase of lockdown consisting in practice meditation exercises at least once a day guided and structured by certified instructors entered on a free online platform. At the end of the program all participants completed a survey. RESULTS: A total of 108 surveys were completed (67.6% male; 32.4% female). Despite the difficult moment of lockdown and the fear linked to the pandemic, 61.9% of interviewed subjects declared a state of general well-being from fair to good linked to the practice of mindfulness. Female subjects (p=0.001), married subjects (p=0.05) and people taking pharmacologic therapy demonstrated (p=0.009) significant improvement in daily management of emotions and practical requests during the early phase of the COVID-19 outbreak. CONCLUSIONS: Mindfulness meditation may be effective in helping people to regulate emotions and to support their mental health during this period of worry and uncertainty.

Web-mediated counseling to counteract the emotional impact of COVID-19 for women with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Interstitial Cystitis (IC) is a chronic and rare disease, more frequent in women. Symptoms of continuous pain can produce psychological disorders, such as anxiety and depression. The spread of COVID-19 pandemic added to distress experienced by patients with IC emotions, such as fear, sadness, boredom, frustration and anger. MATERIALS AND METHODS: A research on very recent literature outlines the necessity for patients facing the complexity of IC during the COVID-19 outbreak to prevent the temporary crisis, to broaden perspectives, to deal with confusion, to support in struggling with unpleasant and unexpected events. CONCLUSIONS: People affected by IC have a psychological vulnerability that needs tailored support interventions, particularly in the COVID era. A multidisciplinary approach offers a personalized treatment through a web-mediated counseling intervention for patients and their caregivers: a space for continuous discussion and reflection can favour a relationship-based process of change aimed at an improvement in quality of life.

Mental health and counseling intervention for hereditary hemorrhagic telangiectasia (HHT) during the COVID-19 pandemic: perspectives from Italy.

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of fibrovascular tissue, transmitted as an autosomal dominant trait. This rare disease can involve one or more organs and clinical manifestations interest several medical specialties. MATERIALS AND METHODS: A review of recent literature and our clinical experience shows that COVID-19 pandemic greatly influences the autonomy and psychic sphere of patients with HHT, causing them further distress. RESULTS: Often patients affected by HHT experience a sense of loneliness due to the rarity of this pathology and COVID-19 pandemic adds a burden for them and their caregivers who have to face emotional experiences that interfere with personal, social and working functioning. CONCLUSIONS: Multidisciplinary approach and web-mediated counseling intervention could offer a valid and personalized support for patients affected by HHT and their caregivers during quarantine due to COVID-19 pandemic.

Ethical questions in human clinical psychopharmacology: should the focus be on placebo administration?

Of all ethical issues in clinical trial designs, only placebo use is dealt with acrimony and unwarranted, rhetoric emphasis. Many misconceptions are biased and may hamper research in the mechanisms of healing and recovery if placebo is banned from clinical trials, as some influential ethicists propose. Current treatments in psychiatry are by no means optimal and may vary in their effect across studies, rendering difficult to find the best available therapeutic method with which to compare new drugs. Because drugs possess specific mechanisms, it is not possible to compare drugs with different mechanisms as to their relevance in the pathophysiology of a given disorder. Placebo acts through non-specific mechanisms and is the ideal control for any disorder whose pathophysiology is relatively unknown and its treatment is still suboptimal. Sticking to short-term patient benefit in a trial reflects an individualistically oriented thinking in contemporary ethics and is likely to limit further research and efforts to better understand the mechanisms of disease and drug action, but also those related to general body reactance and self-healing, which are enhanced by placebo administration. Because in history ethics are swinging between two opposed views, it is possible that in the near future, the balance will move towards communitarianism, which is more likely to better serve long-term patient needs. Ethicists should also consider some other aspects of human experimentation, such as the consistency of research lines and the trend to substitute older drugs with their metabolites or enantiomers.

Early clinical predictors and correlates of long-term morbidity in bipolar disorder.

OBJECTIVES: Identifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). METHODS: We analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. RESULTS: Total % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. CONCLUSIONS: Long-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity.

Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: endothelin-1 system in the human failing heart.

Only scarce information is available on the activity and modifications of the cardiac endothelin (ET)-1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro-ET-1 (ppET-1), ET-converting enzyme-1, and ET(A) and ET(B) receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription-polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ET(A) and ET(B) receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P<0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ET(A) mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ET(B) mRNA was almost exclusively localized on nonmyocyte cells. ET(A)- and ET(B)-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r=0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.

Cardiac growth factors in human hypertrophy. Relations with myocardial contractility and wall stress.

The aim of the present study was to investigate whether and which cardiac growth factors are involved in human hypertrophy, whether growth factor synthesis is influenced by overload type and/or by the adequacy of the hypertrophy, and the relationships between cardiac growth factor formation and ventricular function. Cardiac growth factor formation was assessed by measuring aorta-coronary sinus concentration gradient in patients with isolated aortic stenosis (n=26) or regurgitation (n=15) and controls (n=12). Gene expression and cellular localization was investigated in ventricular biopsies using reverse transcriptase-polymerase chain reaction and in situ hybridization. Cardiac hypertrophy with end-systolic wall stress <90 kdyne/cm2 was associated with a selective increased formation of insulin-like growth factor (IGF)-I in aortic regurgitation and of IGF-I and endothelin (ET)-1 in aortic stenosis. mRNA levels for IGF-I and preproET-1 were elevated and mainly expressed in cardiomyocytes. At stepwise analysis, IGF-I formation was correlated to the mean velocity of circumferential fiber shortening (r=0.86, P<0.001) and ET-1 formation to relative wall thickness (r=0.82, P<0. 001). When end-systolic wall stress was >90 kdyne/cm2, IGF-I and ET-1 synthesis by cardiomyocytes was no longer detectable, and only angiotensin (Ang) II was generated, regardless of the type of overload. The mRNA level for angiotensinogen was high, and the mRNA was exclusively expressed in the interstitial cells. Ang II formation was positively correlated to end-systolic stress (r=0.89, P<0.001) and end-diastolic stress (r=0.84, P<0.001). Multivariate stepwise analysis selected end-systolic stress as the most predictive variable and left ventricular end-diastolic pressure as the independent variable for Ang II formation (r=0.93, P<0.001). In conclusion, the present results indicate that the course of human left ventricular hypertrophy is characterized by the participation of different cardiac growth factors that are selectively related both to the type of hemodynamic overload and to ventricular function.

First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

Evaluation of Right Ventricular Function in the Management of Patients Referred for Left Ventricular Assist Device Therapy.

BACKGROUND: Speckle tracking echocardiography analysis (STE) has recently allowed an in-depth analysis of right ventricular (RV) performance. The aim of the study was to observe RV function by STE in patients with advanced heart failure before and after left ventricular assist device (LVAD) implantation. METHODS: A transthoracic echocardiogram was performed in 19 patients referred for LVAD implant at baseline and with serial echocardiograms after LVAD implantation (Jarvik 2000). All echocardiographic images were analyzed off line by an independent operator to calculate with STE the RV free wall longitudinal strain (RVLS). RESULTS: All the patients, except 4, showed a progressive increase of RVLS after LVAD implant. However, 4 patients, who presented the lowest RVLS values at baseline, presented a further RV failure in the postoperative. The value of -11% represented the empirical preoperative cutoff able to identify patients at greater risk of postimplant RV failure. CONCLUSIONS: RV myocardial deformation may have important clinical implications for the selection and management of LVAD patients. It can be used to evaluate RV function before LVAD implantation, to drive decisional strategy regarding the management of this type of patients, and after LVAD implant for the follow-up.

Endothelin receptors in adult human and swine isolated ventricular cardiomyocytes.

The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridization using specific cDNA probes. The 1251-ET-1 binding, which reached equilibrium in about 120 min (Kobs = 0.051+/-0.003 min(-1)), was only partially displaceable by the addition of a large excess of ET-1 (about 15% with a half-life of 20 min). In equilibrium binding studies, 125I-ET-1 had a Kd of 0.43+/-0.08 nM and a maximum binding (Bmax) of 42.8+/-6.6 fmol/mg protein. ET(A) and ET(B) receptors are represented in human and swine cardiomyocytes with an 85:15 ratio as indicated by the biphasic pattern of competition of both BMS-182874 and BQ-788. In situ hybridization studies confirmed that myocytes mainly expressed mRNA for ET(A), whereas expression of mRNA for the ET(B) subtype was documented in non-myocyte cells. These results showed that ET-1 binds with high affinity and poor reversibility to specific receptors, in both human and swine isolated ventricular cardiomyocytes, without significant species differences.

Video-assisted minimally invasive coronary operations without cardiopulmonary bypass: a multicenter study.

OBJECTIVE: The need to avoid the risks associated with cardiopulmonary bypass has led to the interest in coronary operations without cardiopulmonary bypass. PATIENTS AND METHODS: From April 1994 to September 1995, 44 patients (mean age 63.3 +/- 10.0 years, range 43 to 83 years) were selected for video-assisted coronary artery bypass grafting without cardiopulmonary bypass through a small anterior thoracotomy. Mean preoperative ejection fraction was 50.7% +/- 13.4% (range 20% to 65%). Four patients had left ventricular dysfunction (ejection fraction below 35%). Thirty patients had stable angina (26 with class 3 angina) and 14 had unstable angina. One had recurrent angina (redo). In all cases a small (3.5 to 11 cm) anterior thoracotomy (43 left and one right) was performed and the harvesting of the left internal thoracic artery was video-assisted by thoracoscopy. RESULTS: The left internal thoracic artery was used in 43 cases to graft the left anterior descending coronary artery; the right thoracic mammary was used in one case to graft the right coronary artery; the radial artery was used in one case to perform a T-graft to the first diagonal and first marginal branches. We recorded one death (2.3%) and one case of postoperative low cardiac output syndrome (2.3%). Perioperative myocardial infarction occurred in two cases (4.5%). We did not record noncardiac complications (cerebrovascular complications, kidney failure, prolonged ventilatory support, or wound complications). Supraventricular and ventricular arrhythmias were never detected. CONCLUSION: According to our experience, video-assisted coronary bypass through a small anterior thoracotomy is a new promising technique that can be considered an alternative in most cases to angioplasty and complementary to conventional coronary operations.

Prognostic value of baroreflex sensitivity assessed by phase IV of Valsalva manoeuvre in patients with mild-to-moderate heart failure.

BACKGROUND: In patients with heart failure, impairment of baroreflex function occurs early and contributes to sympathetic activation, however, at present its prognostic role has not been definitively established. AIMS: To evaluate the prognostic significance of baroceptor impairment in patients with different degrees of heart failure. METHODS: We enrolled 52 consecutive patients with heart failure, referred to our institution for functional evaluation. Twenty-eight suffered from ischemic cardiomyopathy and 26 from dilated cardiomyopathy. Thirteen patients were in NYHA class I, 20 in NYHA class II and 19 in class III. All patients underwent baroreflex assessment by phase IV Valsalva manoeuvre using Finapres finger monitoring of arterial blood pressure, echocardiography [with evaluation of left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD) and mean pulmonary artery pressure] and functional evaluation by cardiopulmonary exercise test and 6-min walk corridor test within 2 days of hospital admission. RESULTS: Mean duration of follow-up was 26 months (range 6-35 months). At baseline, evaluation in 13 patients BRS was normal (>5 ms/mmHg), in 17 moderately impaired (1.5-5 ms/mmHg) and in 22 severely depressed (<1.5 ms/mmHg). Baroreflex function was relatively preserved in patients in NYHA class I (5.1+/-2.5) in comparison to patients in NYHA class II and III (2.1+/-2.3 and 2.08+/-1.9 ms/mmHg, respectively). Of the 52 patients who entered the study at the end of follow-up 15 died of cardiac cause and 5 underwent heart transplantation. Survival free from heart transplantation was 62% in patients with normal baroreflex function, 62% in patients with moderate impairment of baroreflex and 66% in patients with major derangement. NYHA class, LVEF, LVFS and LVEDD were significantly associated with event free survival while baroreflex function was not. CONCLUSIONS: Our results suggest that evaluation of BRS impairment by phase IV Valsalva manoeuvre has limited prognostic value in patients with heart failure.

Myocardial ischemic injury and purine metabolism in patients undergoing coronary artery bypass.

OBJECTIVES: High-energy phosphates and their catabolic products were determined in myocardium during coronary artery bypass surgery with blood cardioplegic reperfusion in order to evaluate the effects of aortic cross-clamping and reoxygenation on myocardial purine metabolism. DESIGN AND METHODS: Transmural left ventricular biopsy specimens were taken with ITu-Cut biopsy needles, before aortic cross-clamping, before cross-clamp removal and after 30' of reperfusion; perchloric extracts of the material were analyzed for nucleotide content by capillary zone electrophoresis (CZE). The CZE procedure used separates the complete spectrum of purine metabolites in myocardial extracts obtained from 0.6-8.6 mg biopsy material. RESULTS: The basal values of ATP/ADP ratio and energy charge were low, IMP content was high. After the ischemic period, ATP levels further decreased and IMP, nucleosides and bases accumulated. After reperfusion, nucleoside and base basal levels, but not energy charge, were restored to some extent. CONCLUSIONS: The study arises the problem of myocardial preservation during heart surgery. In this investigation, capillary electrophoresis was an extremely adaptable technique for the evaluation of ischemic injury and could be useful in studying the effects of cardioplegic solutions.