Antonello Bellomo

The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Functional lateralization of the sensorimotor cortex in patients with schizophrenia: effects of treatment with olanzapine.

BACKGROUND Earlier cross-sectional studies with functional magnetic resonance imaging (fMRI) in treated patients with schizophrenia have reported abnormalities of cortical motor processing, including reduced lateralization of primary sensory motor cortex. The objective of the present longitudinal study was to evaluate whether such cortical abnormalities represent state or trait phenomena of the disorder. METHODS Seventeen acutely ill, previously untreated patients were studied after 4 weeks and after 8 weeks of olanzapine therapy. Seventeen matched healthy subjects served as control subjects. All subjects underwent two fMRI scans 4 weeks apart during a visually paced motor task using a simple periodic block design. Functional magnetic resonance imaging data were analyzed in Statistical Parametric Mapping (SPM99). Region of interest analyses were used to determine a laterality quotient (an index of lateralization) of motor cortical regions. RESULTS The fMRI data indicated that patients had reduced activation of the primary sensory motor cortex at 4 weeks but not at 8 weeks; however, the laterality quotient in the primary sensory motor cortex was reduced in patients at both time points. CONCLUSIONS These results suggest that some cortical abnormalities during motor processing represent state phenomena, whereas reduced functional lateralization of the primary sensory motor cortex represents an enduring trait of schizophrenia.

Alexithymia and Psychopathology in Patients with Psychiatric and Functional Gastrointestinal Disorders

Background: Alexithymia and psychopathology may influence the way individuals experience psychological distress and somatic symptoms. This study evaluated patients referred to psychiatric and gastroenterologic outpatient settings in order to investigate the levels of alexithymia and psychopathology, and the possible role of alexithymia in symptom perception and health care utilization. The association between psychiatric disorders and functional gastrointestinal disorders (FGIDs) was also assessed. Methods: Psychopathology (by the Revised 90-item Symptom Checklist), alexithymia (by the 20-item Toronto Alexithymia Scale), and gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale) were evaluated in 52 psychiatric outpatients and 58 medical outpatients with FGIDs. Two comorbid subgroups of 25 psychiatric patients with FGIDs and 38 FGID patients with psychiatric disorders were formed and compared. Results: Forty-eight percent of the psychiatric patients had associated FGIDs, and 65.5% of the FGID patients had associated psychiatric disorders. The FGID patients had significantly less psychopathology, but significantly higher alexithymia and more severe gastrointestinal symptoms, than the psychiatric patients. In the comparison of the two subgroups with comorbidity, FGID patients with psychiatric disorders were still more alexithymic and had less psychopathology than psychiatric patients with FGIDs, but gastrointestinal symptoms were not significantly different. Conclusion: Patients with ‘functional’ gastrointestinal symptoms attending a medical care service are likely to be highly alexithymic, whereas those attending a psychiatric care service are likely to show severe psychopathology. Alexithymia seems to influence the presentation of ‘functional’ somatic symptoms and the type of health care utilization.

Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

The failure of several Phase II/III clinical trials in Alzheimers disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.

Is alexithymia related to negative symptoms of schizophrenia? : A preliminary longitudinal study

Background: Alexithymic features are close to anhedonia, blunted affect, and alogia that are also characteristics of the negative symptoms of schizophrenia. This study aimed to evaluate whether alexithymia is associated with negative symptoms and is related to the change of schizophrenic symptoms over time. Sampling and Methods: A consecutive sample of 29 schizophrenic outpatients was evaluated at baseline and at 3, 6, and 12 months during appropriate treatment. They completed the Positive and Negative Syndrome Scale, the Montgomery and Asberg Depression Rating Scale, the Global Assessment of Functioning Scale, and the 20-item Toronto Alexithymia Scale at any time points. Results: The psychiatric scale scores showed significant symptom improvement over time but were unrelated to the alexithymia score that was instead stable over time. Hierarchical regression showed that the 20-item Toronto Alexithymia Scale at baseline was the sole predictor of alexithymia at 12 months, after controlling for psychopathology and psychological functioning. Conclusions: Alexithymia was unrelated to negative symptoms, suggesting it is an independent and separate construct from schizophrenia. As expected, the negative symptoms were associated instead with illness-related aspects of depression and psychosocial functioning. Caution should be expressed in generalization mainly because this study is limited by the small sample size.

Psychosocial Functioning in Consultation-Liaison Psychiatry Patients: Influence of Psychosomatic Syndromes, Psychopathology and Somatization

Background:This study investigated whether the Diagnostic Criteria for Psychosomatic Research (DCPR) were able to predict psychosocial functioning in addition to psychiatric diagnoses and somatization in consultation-liaison psychiatry (CLP) patients. Method: A consecutive sample of 208 CLP patients were recruited and assessed for sociodemographic and medical data, psychopathology (SCID), psychosomatic syndromes (DCPR structured interview) and somatization (SCL-90-R SOM scale and multisomatoform disorder, MSD). The main endpoints were the mental and physical components of psychosocial functioning (SF-36). Results: A total of 185 (89%) patients had any psychiatric diagnosis, 51 (25%) had MSD positive criteria, 176 (85%) had any DCPR syndrome, and 105 (51%) had multiple DCPR syndromes. Although psychiatric and psychosomatic syndromes were variously associated with psychosocial functioning, hierarchical regression and effect size analyses showed that only DCPR syndromes, particularly demoralization and health anxiety, with somatization but not DSM-IV psychopathology independently predicted poor psychosocial functioning. Conclusions:The presence of psychosomatic syndromes, assessed with DCPR criteria, and high levels of somatization had larger effect size and were independent predictors of the mental and physical components of psychosocial dysfunction, over and above psychopathology. The DCPR classification can provide CLP professionals with a set of sensitive diagnostic criteria for a comprehensive clinical evaluation of psychosomatic syndromes that might play a significant mediating role in the course and the outcome of medical patients referred for psychiatric consultation.

Type A behaviour: a reappraisal of its characteristics in cardiovascular disease

Aims:  The role of type A behaviour in cardiovascular disease is controversial and most of the research is based on self‐rating scales. The aim of this study was to assess the prevalence of type A behaviour in cardiology and in other medical settings using reliable interview methods that reflect its original description.

Subtyping depression in the medically ill by cluster analysis

BACKGROUND There is increasing awareness of the need of subtyping major depressive disorder, particularly in the setting of medical disease. The aim of this investigation was to use both DSM-IV comorbidity and the Diagnostic Criteria for Psychosomatic Research (DCPR) for characterizing depression in the medically ill. METHODS 1700 patients were recruited from 8 medical centers in the Italian Health System and 1560 agreed to participate. They all underwent a cross-sectional assessment with DSM-IV and DCPR structured interviews. 198 patients (12.7%) received a diagnosis of major depressive disorder. Data were submitted to cluster analysis. RESULTS Two clusters were identified: depressed somatizers and irritable/anxious depression. The somatizer cluster included 58.6% of the cases and was characterized by DCPR somatization syndromes (persistent somatization, functional somatic symptoms secondary to a psychiatric disorder, conversion symptoms, and anniversary reactions) and DCPR alexithymia. The anxious/irritable cluster had 41.4% of the total sample and included DCPR irritable mood and type A behavior and DSM-IV anxiety disorders. LIMITATIONS The study has limitations due to its cross-sectional nature. Further, these findings require additional validation in another sample. CONCLUSIONS The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, irritable mood, type A behavior and alexithymia, as encompassed by the DCPR. Subtyping major depressive disorder may yield improved targets for psychosomatic research and treatment trials.

A cluster analysis-derived classification of psychological distress and illness behavior in the medically ill.

BACKGROUND The classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill. METHOD A cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate. RESULTS Three clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization. CONCLUSIONS Two-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimers Association guidelines for Alzheimers disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.