Roberto Brugnoli

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.

Emotion recognition impairment is present early and is stable throughout the course of schizophrenia

Individuals with schizophrenia experience problems in the perception of emotion throughout the course of the disorder. Few studies have addressed the progression of the deficit over time. The present investigation explores face emotion recognition (FER) performance throughout the course of schizophrenia. The aim of the study was to test the hypotheses that: 1) FER impairment was present in ultra high-risk (putatively prodromal) individuals, and that 2) impairment was stable across the course of the illness. Forty-three individuals with a putative prodromal syndrome, 50 patients with first episode of schizophrenia, 44 patients with multi-episode schizophrenia and 86 unaffected healthy control subjects were assessed to examine emotion recognition ability. ANCOVA analysis adjusted for possible confounder factors and subsequent planned contrasts with healthy controls was undertaken. The results revealed deficits in recognition of sadness and disgust in prodromal individuals, and of all negative emotions in both first-episode and multi-episode patients. Furthermore, there were no significant differences between clinical groups. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of emotional recognition impairment before the onset of full-blown psychosis. Moreover, the deficit remains stable over the course of illness, fitting the pattern of a vulnerability indicator in contrast to an indicator of chronicity or severity.

Which somatic symptoms are associated with an unfavorable course in Asian patients with major depressive disorder

OBJECTIVE To investigate the impact of somatic symptoms on the severity and course of depression in Asian patients treated for an acute episode of major depressive disorder (MDD). METHODS Three-month prospective observational study of 917 patients with MDD in psychiatric care settings of which 909 had complete main baseline data. Depression severity was assessed using the physician-rated Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD17), and somatic symptoms were assessed using the patient-rated 28-item Somatic Symptom Inventory (SSI). Cluster analysis using baseline SSI scores grouped patients into 3 clusters with no/few, moderate or severe somatic symptoms. Four factors of SSI (pain, autonomic symptoms, energy, and central nervous system) were defined and regression analyses identified which factors were associated with remission and response at 3 months follow-up. RESULTS Baseline depression severity (HAMD17 and CGI-S scores) was associated with more severe somatic symptoms. Remission rates differed between clusters of patients: 68.4%, 54.7% and 29.3% for no/few, moderate and severe somatic symptoms, respectively (p<0.0001). Corresponding response rates were 81.8%, 72.1% and 55.2% (p<0.0001). Pain symptoms were the somatic symptoms most associated with these clinical outcomes at 3 months. LIMITATIONS Only patients diagnosed with MDD in psychiatric care were assessed. CONCLUSIONS Somatic symptoms are frequent among Asian patients in psychiatric care for MDD and are associated with greater clinical severity and lower response and remission rates. Among somatic symptoms, pain symptoms have the greatest prognostic value and should be taken into account when treating patients with depression.

Efficacy of Add-On Deep Transcranial Magnetic Stimulation in Comorbid Alcohol Dependence and Dysthymic Disorder: Three Case Reports

BACKGROUND Craving for alcohol is associated with abnormal activation in the dorsolateral prefrontal cortex. Deep transcranial magnetic stimulation (dTMS) has shown promise in the treatment of depression. There are few treatment options for treatment-resistant dysthymic disorder comorbid with alcohol use disorder. OBJECTIVE To investigate the possible anticraving efficacy of bilateral dorsolateral prefrontal cortex high-frequency dTMS in 3 patients with comorbid long-term DSM-IV-TR dysthymic disorder and alcohol use disorder. METHOD Three patients with alcohol use disorder with dysthymic disorder in their detoxification phase (abstaining for > 1 month) underwent twenty 20-minute sessions of 20 Hz dTMS over the dorsolateral prefrontal cortex over 28 days between 2011 and 2012. Alcohol craving was rated with the Obsessive Compulsive Drinking Scale and depressive symptoms with the Hamilton Depression Rating Scale. RESULTS All 3 patients responded unsatisfactorily to initial intravenous antidepressant and antianxiety combinations but responded after 10 dTMS sessions, improving on both anxiety-depressive symptoms and craving. This improvement enabled us to reduce antidepressant dosages after dTMS cycle completion. DISCUSSION High-frequency bilateral dorsolateral prefrontal cortex dTMS with left prevalence was found to produce significant anticraving effects in alcohol use disorder comorbid with dysthymic disorder. The potential of dTMS for reducing craving in patients with substance use disorder deserves to be further investigated.

Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: A comparison with standard treatment

Abstract Objectives. Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. Methods. We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). Results. At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P < 0.001 and P < 0.02, respectively). Conclusions. High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated.

Risk factors for suicide behaviors in the observational schizophrenia outpatient health outcomes (SOHO) study

BackgroundTo identify risk factors for suicide using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study).MethodsBaseline characteristics of 8,871 adult patients with schizophrenia were included in a logistic regression post-hoc analysis comparing patients who attempted and/or committed suicide during the study with those who did not.Results384 (4.3%) patients attempted or committed suicide. Completed suicides were 27 (0.3%). The significant risk factors for suicide behaviors were previous suicidality, depressive symptoms, prolactin-related adverse events, male gender and history of hospitalization for schizophrenia.ConclusionsIn view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.

Tobacco smoking and suicidal ideation in school-aged children 12-15 years old: impact of cultural differences.

ABSTRACT This cross-sectional study examined the association between tobacco smoking and suicidal ideation in school-aged children from 9 countries in Africa, the Americas, and the Western Pacific region. Data were collected through the Global school-based Student Health Survey, a collaborative surveillance project between the World Health Organization, the United Nations, UNICEF, UNESCO, UNAIDS, and the U.S. Centers for Disease Control and Prevention. Suicidal ideation, tobacco smoking, and drug and alcohol use were included in loglinear models to analyze higher order interactions among suicidality and regional and country differences separately for boys and girls. School-aged children who reported suicidal ideation had a higher risk of smoking tobacco even after controlling for drug and alcohol misuse. Furthermore, analyses indicated higher order interactions between suicidal ideation and countries belonging to different regions with different exposure to tobacco smoking among school-aged children. Future studies analyzing the mechanism and sequencing of the relationship among suicidal ideation and tobacco smoking should explore cultural factors.

Executive functions in obsessive–compulsive disorder: An activation likelihood estimate meta-analysis of fMRI studies

Abstract Objectives: To identify activation changes assessed in functional magnetic resonance imaging (fMRI) studies of obsessive–compulsive disorder (OCD) through Activation Likelihood Estimate meta-analysis. Methods: We included 28 peer-reviewed standard stereotactic space studies assessing adult OCD patients (OCDpts) vs. healthy controls (HCs) with fMRI during executive task performance. Results: In within-group analyses, HCs showed task-related activations in bilateral inferior frontal gyri, right middle frontal gyrus, right inferior parietal lobule, right claustrum, bilateral cingulate gyri, and left caudate body. OCDpts showed task-related left-sided activations in the superior, medial, and inferior frontal gyri, and thalamus, and bilateral activations in the middle frontal gyri, inferior parietal lobule, and insular cortices. Subtraction analysis showed increased left middle frontal gyrus activation in OCDpts. In between-groups analyses, OCDpts hypoactivated the right caudate body, left putamen, left ACC, and right medial and middle frontal gyri. Right caudate hypoactivation persisted also after applying Family‐wise error algorithms. Conclusions: This meta-analysis confirms that during executive functioning OCDpts show a functional deficit of the right caudate body, which could represent a major neural functional correlate of their illness.

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder

INTRODUCTION Cocaine dependence is a substantial public health problem. The aim of this study is to evaluate the effect of high frequency deep transcranial magnetic stimulation (dTMS) on craving in patients with cocaine use disorder (CUD). METHODS Seven men (mean age, 48.71 years; standard deviation [SD], 9.45; range 32-60 years) with CUD and no concurrent axis 1 or 2 disorder save nicotine abuse, underwent three sessions of alternate day 20Hz dTMS in 20 trains delivered to the dorsolateral prefrontal cortex (DLPFC) preferentially to the left hemisphere, for 12 sessions spread over one month, added to unchanged prior drug treatment. We used a visual analogue scale (VAS) to measure cocaine craving the week before, each week during, and one month after dTMS treatment. RESULTS DLPFC stimulation significantly reduced craving over time: within-subjects main effect of time of treatment (ANOVA, F[3,18]=46.154; p<0.001; η(2)=0.88). The reduction of craving from baseline was significant at two weeks (p<0.001), and four weeks (p<0.001) of treatment, and at the week eight, four weeks after treatment interruption (p=0.003), although the increase of craving was significant from week four and eight (p=0.014). CONCLUSION dTMS over left DLPFC reduced craving in CUD patients in a small sample that is to be considered preliminary. However, maintenance sessions would be needed to maintain the achieved results. Our findings highlight the potential of noninvasive neuromodulation as a therapeutic tool for cocaine addiction.

Do concomitant pain symptoms in patients with major depression affect quality of life even when taking into account baseline depression severity

Background: Patients with major depressive disorder (MDD) may suffer from concomitant pain symptoms. The aim of this study is to determine whether the presence of painful physical symptoms (PPS) influences quality of life when taking into account baseline depression severity. Methods: Patients with a new or first episode of MDD (n = 909) were enrolled in a 3-month prospective observational study in East Asia. The Hamilton Depression Rating Scale, Clinical Global Impression-Severity score, Somatic Symptom Inventory, and EuroQoL questionnaire-5 Dimensions (EQ-5D) and EQ-Visual Analogue Scale (EQ-VAS) were assessed at baseline and 3 months’ follow-up. The presence of PPS was defined as a mean score of ≥2 on the Somatic Symptom Inventory pain-related items. Regression analyses determined predictors of quality of life at 3 months, adjusting for age, sex, depressive symptoms, overall severity, and quality of life at baseline. Results: PPS were present (PPS+) at baseline in 52% of patients. During the 3-month follow-up, EQ-VAS scores improved from 47.7 (standard deviation [SD] 20.6) to 72.5 (SD 20.4), and EQ-5D improved from 0.48 (SD 0.34) to 0.80 (SD 0.26). At 3 months, mean EQ-VAS was 66.4 (SD 21.2) for baseline PPS+ patients versus 78.5 (SD 17.6) for baseline PPS− patients, and mean EQ-5D was 0.71 (SD 0.29) versus 0.89 (SD 0.18). PPS+ at baseline was a significant predictor of quality of life at 3 months after adjusting for sociodemographic and baseline clinical variables. Conclusion: The presence of painful physical symptoms is associated with less improvement in quality of life in patients receiving treatment for major depression, even when adjusting for depression severity.