Martino Belvederi Murri

Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.

BACKGROUND Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. METHOD Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. RESULTS Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). CONCLUSIONS Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF.

Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis

Background: Cortisol and inflammatory markers have been increasingly reported as abnormal at psychosis onset. The main aim of our study was to investigate the ability of these biomarkers to predict treatment response at 12 weeks follow-up in first episode psychosis. Methods: In a longitudinal study, we collected saliva and blood samples in 68 first episode psychosis patients (and 57 controls) at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. Moreover, we repeated biological measurements in 39 patients at the same time we assessed the response. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ (IFN-γ) levels were analyzed from serum samples. Patients were divided into Non-Responders (n = 38) and Responders (n = 30) according to the Remission symptom criteria of the Schizophrenia Working Group Consensus. Results: At first onset, Non-Responders had markedly lower CAR (d = 0.6, P = .03) and higher IL-6 and IFN-γ levels (respectively, d = 1.0, P = .003 and d = 0.9, P = .02) when compared with Responders. After 12 weeks, Non-Responders show persistent lower CAR (P = .01), and higher IL-6 (P = .04) and IFN-γ (P = .05) when compared with Responders. Comparison with controls show that these abnormalities are present in both patients groups, but are more evident in Non-Responders. Conclusions: Cortisol and inflammatory biomarkers at the onset of psychosis should be considered as possible predictors of treatment response, as well as potential targets for the development of novel therapeutic agents.

Vitamin D and psychosis: Mini meta-analysis

Individuals with psychotic disorders are more likely to have vitamin D (VD) deficiency, while evidence suggests VD could have pathophysiological roles. We summarized meta-analytically the available evidence on VD levels in psychotic disorders in comparison with healthy controls and other psychiatric illnesses. We found seven studies, all reporting insufficient VD levels in patients with psychosis. Schizophrenia had a medium effect size for lower VD than healthy controls, and a trend for lower levels than other psychoses. There were non-significant differences between schizophrenia and major depression. No study has investigated the potential psychotropic effects of VD supplementation in patients with psychosis.

Recognition and treatment of depression in primary care: Effect of patients' presentation and frequency of consultation

OBJECTIVE Primary care physicians (PCPs) are expected to recognize depression and appropriately prescribe antidepressants. This article investigated the single and combined effects of different patient presentations and frequency of visits on detection and antidepressant use. METHODS Data came from an Italian nationwide survey on depressive disorders in primary care, involving 191 PCPs and 1910 attenders. Two hundred fifty patients suffering from major or subthreshold depression were compared in relation to their presentation (psychological, physical, and pain) and frequency of visits (low and high). RESULTS Recognition of depression significantly varied according to both presentation and frequency of visits. When compared to patients with psychological complaints, the odds ratios for nonrecognition of depression were higher for patients presenting with physical symptoms [2.3; 95% confidence interval (CI)=1.1-5.3] and with pain (4.1; 95% CI=1.6-9.9). Subjects who rarely attended the practice were 2.3 times less likely to receive a diagnosis of depression, compared with those having a high frequency of visits (95% CI=1.2-4.6). Similarly, patients presenting with physical symptoms or with pain and those with a low frequency of visits were rarely treated with antidepressants. The combination of physical or pain presentation with low frequency of visits further increased the risk for nonrecognition, which was sixfold that of the reference category. CONCLUSIONS Some subgroups of depressed patients still run a high risk of having their depression unrecognized by the PCP. Screening for depression among patients presenting with pain might be useful in order to improve recognition and management.

The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Performance in Treatment-Resistant Depression. A Systematic Review

Background: Major depressive disorder (MDD) is a disabling illness associated with significant functional and psychosocial impairment. Although many psychopharmacological agents are currently available for its treatment, many MDD patients suffer from treatment-resistant depression (TRD). Methods: A systematic review of the current literature (Pubmed/Medline, Scopus and ScienceDirect search) has been conducted with the primary aim to investigate the role of repetitive transcranial magnetic stimulation (rTMS) in improving neurocognition in patients with TRD. Studies were included according to the following criteria: (a) being an original paper in a peer-reviewed journal and (b) having analyzed the effect of rTMS on neurocognitive functioning in TRD. Results: The combined search strategy yielded a total of 91 articles, of which, after a complete analysis, 22 fulfilled our inclusion criteria. Based on the main findings, most of the selected studies suggested the existence of a trend towards improvements in the neurocognitive profile using rTMS. Negative findings have also been reported. However, most studies were limited by their small sample size or included mixed samples, or the adopted single-blind designs potentially biased the blinding of the study design. Conclusion: rTMS is a noninvasive brain stimulation that may be considered a valuable and promising technique for cognitive enhancement in TRD.

Anxiety Symptoms in 74+ Community-Dwelling Elderly: Associations with Physical Morbidity, Depression and Alcohol Consumption

Objective Anxiety among community-dwelling older adults has not been studied sufficiently. The aims of this cross-sectional population-based study were to estimate the point prevalence of clinically relevant anxiety symptoms and to describe their socio-demographic and clinical features, with particular focus on the association with somatic illnesses. Methods Three-hundred-sixty-six non-demented older adults (mean age 83.7±6.2, range 74–99 years) from the Faenza Project (Northern Italy) were assessed using the Cambridge Mental Disorders of the Elderly Examination-Revised (CAMDEX-R) and the Geriatric Anxiety Inventory short form (GAI-sf). Multi-adjusted regression analyses were used to estimate Odds Ratio (OR) and 95% Confidence Intervals (95% CI). Results Clinically relevant anxiety symptoms occurred in one out of five participants (point prevalence 21.0%) and were significantly associated with depression (OR 5.6 per rank; 95% CI: 3.1–10.1), physical morbidity (OR 3.5 per illness; 95% CI: 1.0–11.9) and female gender (OR 2.8; 95% CI: 1.4–5.5). Further, there were significant associations with a consumption of alcohol exceeding 1 alcoholic unit/day. Conclusions Anxiety symptoms are very common in older subjects, especially when medically ill. Depression and alcohol consumption often co-occur with late-life anxiety symptoms, thus requiring special attention in daily clinical practice.

Cyclothymic temperament rather than polarity is associated with hopelessness and suicidality in hospitalized patients with mood disorders

BACKGROUND The aim of the present study was to assess sociodemographic and clinical differences between inpatients with major mood disorders (bipolar disorder - BD - and major depression - MDD) and the cyclothymic phenotype (CYC), and pure BDs or MDDs. METHODS Participants were 281 adult inpatients (134 men and 147 women) consecutively admitted to the Department of Psychiatry of the Sant׳Andrea University Hospital in Rome, Italy, between January 2008 and June 2010. The patients completed the Hamilton Scale for Depression (HAMD17), the Young Mania Rating Scale, the TEMPS-A (Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire), and the Beck Hopelessness Scale. RESULTS 38.7% of the MDD patients and 48.3% of the BD patients satisfied criteria to be included in the cyclothymic groups. Above 92% of the patients with the cyclothymic phenotype reported suicidal ideation at the item #3 of the HAMD17. Furthermore, patients with the cyclothymic phenotype reported higher hopelessness than other patients. LIMITATIONS Our results are potentially limited by the small number of MDD-CYC patients included in the sample. CONCLUSIONS Our results support the clinical usefulness of the concept of soft bipolar spectrum. Patients with the cyclothymic phenotype differ from pure MDD patients and BD patients for temperamental profile and clinical variables.

Vitamin D supplements in geriatric major depression

Geriatric depression is associated with a high prevalence of vitamin D deficiency (Hoogendijk et al., 2008; Chan et al., 2010)—possibly playing a pathophysiological role (Bertone‐Johnson, 2009). Indeed, vitamin D has been demonstrated to improve subjective psychological status (Vieth et al., 2004; Jorde et al., 2008), but it is unknown if this might hold true also among patients with major depression. Older patients have a high risk for both treatment‐resistant depression and vitamin D deficiency: if vitamin D had antidepressant properties, this might improve the management of geriatric depression. Therefore, our study aimed at evaluating the safety and efficacy of vitamin D supplementation among older patients having major depression.

Food Cravings Questionnaire–Trait (FCQ–T) Discriminates Between Obese and Overweight Patients With and Without Binge Eating Tendencies: The Italian Version of the FCQ–T

Food craving (FC) might play an important role in the course of eating disorders and obesity. The question of its measurement has particular importance in relation to the dramatic growth in obesity rates and its relevance for public health. The aim of this study was to investigate the psychometric properties of the Italian version of the Food Cravings Questionnaire–Trait (FCQ–T) in overweight and obese patients who were attending weight loss programs, and its efficiency in discriminating patients with binge eating. Participants were 497 (411 women, 86 men) overweight and obese patients in treatment with low-energy diet therapy. We used structural equation modeling to compare 3 factor models tested in previous studies (a 6-factor model, an 8-factor model, and a 9-factor model), which indicated that the 9-factor model has a better fit over the competing models. The FCQ–T had good internal consistency (Cronbachs α of.96 for the total score, and between.76 and.92 for subfactors), and was able to discriminate patients with clinical-level binge eating from those with probable and without binge eating with an efficiency of.74 (sensitivity =.64, specificity =.78). FCQ–T scores were sensitive to changes associated with treatment only for patients who started dietary restriction between the baseline and the follow-up assessment, but not for patients who were already observing dietary restrictions at the time of the baseline assessment. These results suggest that the FCQ–T could be a potentially useful measure for the screening of binge eating problems in overweight and obese patients while in treatment.

Biased processing of neutral facial expressions is associated with depressive symptoms and suicide ideation in individuals at risk for major depression due to affective temperaments

BACKGROUND To elucidate whether abnormal facial emotion processing represents a vulnerability factor for major depression, some studies have explored deficits in emotion processing in individuals at familial risk for depression. Nevertheless, these studies have provided mixed results. However, no studies on facial emotion processing have been conducted in at-risk samples with early or attenuated signs of depression, such as individuals with affective temperaments who are characterized by subclinical depressive moods, cognitions, and behaviors that resemble those that occur in patients with major depression. METHODS Presence and severity of depressive symptoms, affective temperaments, death wishes, suicidal ideation, and suicide planning were explored in 231 participants with a mean age 39.9 years (SD=14.57). Participants also completed an emotion recognition task with 80 emotional face stimuli expressing fear, angry, sad, happy, and neutral facial expressions. RESULTS Participants with higher scores on affective temperamental dimensions containing a depressive component, compared to those with lower scores, reported more depressive symptoms, death wishes, suicide ideation and planning, and an increased tendency to interpret neutral facial expressions as emotional facial expressions; in particular, neutral facial expressions were interpreted more negatively, mostly as sad facial expressions. However, there were no group differences in identification and discrimination of facial expressions of happiness, sadness, fear, and anger. CONCLUSIONS A negative bias in interpretation of neutral facial expressions, but not accuracy deficits in recognizing emotional facial expressions, may represent a vulnerability factor for major depression. However, further research is needed.