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Vagus nerve stimulation (VNS) has been shown to be effective for treatment-resistant depression (TRD). However, long-term (5 years) studies on the efficacy and tolerability of this treatment have been lacking. Here, we report a long-term clinical follow-up of 5 patients with severe and long-standing TRD, who received a VNS implant.Of the initial 6 patients with TRD implanted with VNS at our center, 5 of them were followed for 6 to 12 years after implantation. Primary efficacy outcomes were clinical response and improved functioning at follow-up visits. The primary safety outcome was all-cause discontinuation, and the secondary safety outcomes were the number and the severity of adverse events.The VNS implant was associated with a sustained response (10 years) in terms of clinical response and social, occupational, and psychological functioning in 3 patients. Two patients dropped out after 6 and 7 years of treatment, respectively. Vagus nerve stimulation was well tolerated by all patients, who reported only mild adverse effects. One patient, who discontinued concomitant drug treatment, had a hypomanic episode in the 10th year of treatment. The parameters of the VNS device were fine-tuned when life stressors or symptom exacerbation occurred.Our case series showed that VNS can have long-term and durable effectiveness in patients with severe multiepisode chronic depression, and this could be associated with its neuroplastic effects in the hippocampus. In light of good general tolerability, our findings support VNS as a viable treatment option for TRD.

Catatonia is a psychomotor syndrome characterized by heterogeneous motor, behavioral and affective alterations, and, in some cases, neurovegetative abnormalities that can be life-threatening. Although the prevalence estimates of catatonia are 10-20% of the hospitalized population, its clinical recognition remains a challenge for most clinicians. Differently from other catatonia rating scales, the Northoff Catatonia Rating Scale (NCRS) also evaluates the affective alterations that patients experience during catatonia and thus provides a more inclusive assessment of the alterations associated with this condition. To provide clinicians with a valuable tool for diagnosis, we translated the NCRS in Italian and validated it on a sample of 52 hospitalized patients with psychiatric disorders.An Italian version of the NCRS was prepared using the forward-backwards translation from English and administered to a sample of 52 in-patients (age 46.9±2.37 years). The inter-rater reliability, score correlations, internal coherence and decision statistics were computed.The inter-rater agreement was higher for the motor subscale (100% agreement) than for the behavioral (94%) or affective subscales (92.3%). The inter-rater agreement was 100% for the diagnosis of catatonia. The NCRS correctly identified all patients with catatonia according to DSM-5 (sensitivity= 100%) and had a specificity of 88.9%, and its subscale scores were highly inter-correlated.This validation shows that the NCRS yields a good accuracy in diagnosing catatonia and high inter-rater reliability. Moreover, the high correlation between its subscales supports the view that catatonia is a multi-faceted truly psycho-motor syndrome. In conclusion, the validation and Italian translation of the NCRS provides the clinicians with a helpful tool for diagnosing catatonia which is easy to use and assesses the full psychomotor complexity of the syndrome.

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring).

Objective: This study aimed to analyze the longitudinal course of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in patients with cardiac disease after heart surgery (HS). Methods: We conducted a systematic review and random-effects meta-analysis of cohort studies in patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days thereafter. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken. Results:We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter-defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g = 0.32; 95% confidence interval [CI] = 0.25 to 0.39; p < .001) and anxiety improved after HS (g = 0.52; 95% CI = 0.43 to 0.62; p < .001), whereas PTSD symptoms worsened (g = -0.42; 95% CI = -0.80 to -0.04; p = .032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure and persisted for 1 year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension, and dyslipidemia and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was nonsignificant. Conclusions: Depressive and anxiety symptoms improve for 1 year after HS, whereas PTSD symptoms might worsen. Older patients and those withmetabolic comorbidities, valve disease, or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimers disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted. Funding Agencies|National Institute for Health Research (NIHR)National Institute for Health Research (NIHR) [PDF-2018-11-ST2-020]; National Council for Scientific and Technological DevelopmentNational Council for Scientific and Technological Development (CNPq) [CNPQ-1B]; Program of Academic Productivity (PIPA) of the University of Sao Paulo Medical School; Pakistan Institute of Living and Learning (PILL); Physicians Services Incorporated (PSI) Foundation; Stanley Medical Research Institute (SMRI); Blackmores Institute Fellowship; NIH, Cooperative Research Centre; Cancer Council of VictoriaCanadian Institutes of Health Research (CIHR)Cancer Council Victoria; Stanley Medical Research Foundation; Medical Benefits Fund; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia; Medical Research Futures Fund; Beyond Blue; Rotary Health; A2 milk company; Meat and Livestock Board; Woolworths; Avant; Harry Windsor Foundation; NHMRCNational Health and Medical Research Council of Australia [1059660, 1156072]; Alzheimers AssociationAlzheimers Association [PTC-18-543823]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AG046543]; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR) [MOP 201803PJ8]; Alzheimers Drug Discovery Foundation [1012358]; Alzheimer Society of Canada [15-17]; Brain and Behaviour Foundation; Generalitat de Catalunya (PERIS); Spanish Ministry of Science, Innovation and Universities (CIBERSAM); EU Horizon 2020; Stanley Medical Research Institute; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R37MH068376]; NARSAD Distinguished Investigator AwardNARSAD; Brain & Behavior Research FoundationNARSAD [26950]; Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR); National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA); Alzheimer Society of Canada; Alzheimers Association USAlzheimers Association; Alzheimers Drug Discovery Foundation

Few studies have investigated alterations of olfactory neuroepithelium (ONE) as a biomarker of schizophrenia, and none its association with cognitive functioning.Fresh ONE cells from twelve patients with schizophrenia and thirteen healthy controls were collected by nasal brushing, cultured in proper media and passed twelve times. Markers of cell proliferation (BrdU incorporation, Cyclin-D1 and p21 protein level) were quantified.Cognitive function was measured using Brief Neuropsychological Examination-2.proliferation of ONE cells from schizophrenic patients at passage 3. Secondary outcome: association between alteration of cell proliferation and cognitive function.Fresh ONE cells from patients showed a faster cell proliferation than those from healthy controls at passage 3. An opposite trend was observed at passage 9, ONE cells of patients with schizophrenia showing slower cell proliferation as compared to healthy controls. In schizophrenia, overall cognitive function (Spearman's rho -0.657, p 0.01), verbal memory - immediate recall, with interference at 10 s and 30 s (Spearman's rho from -0.676 to 0.697, all p 0.01) were inversely associated with cell proliferation at passage 3.Fresh ONE cells collected by nasal brushing might eventually represent a tool for diagnosing schizophrenia based upon markers of cell proliferation, which can be easily implemented as single-layer culture. Cell proliferation at passage 3 can be regarded as a promising proxy of cognitive functioning in schizophrenia. Future studies should replicate these findings, and may assess whether ONE alterations are there before onset of psychosis, serving as an early sign in patients with at risk mental state.

I ntroduction Vagus nerve stimulation (VNS) is a neuromodulation technique approved for Treatment-Resistant Depression (TRD).Evidence regarding its long-term efficacy and safety is still scarce. Objectives To descriptively report a case series of 3 patients undergoing adjunctive VNS for TRD with an over 10-year follow-up. Methods We investigated outcomes of clinical interest in patients with ongoing VNS for at least 10 years after the device implantation. They had participated in a larger single-arm interventional study conducted at the University Hospital of Padua. They were diagnosed with chronic unipolar (1), recurrent unipolar (1), and bipolar (1) TRD. Results Our 3 cases had an average 14-year history of psychiatric disease before surgery. Afterward, all subjects achieved clinical remission within two years. 2 patients experienced relapses within the first 4 years of treatment (respectively, 1 and 2 episodes). The other case showed a recurrent trend of brief relapses every two years. Only 1 individual needed to be admitted to the psychiatric unit once. None of them committed suicidal attempts. Prescription of antidepressants remained almost unchanged after the first two years. 2 individuals improved and 1 maintained their working position. Common adverse events were voice alteration (3/3), neck pain (2/3), and cough (2/3). Conclusions Very few cases of 10-year VNS for TRD have been reported so far. For our subjects, VNS was most likely to have a major impact on the clinical course of the disease. This treatment can be a safe and effective adjunctive intervention in a subgroup of patients with TRD.

Major depression is a high-prevalence mental disease with major socio-economic impact, for both the direct and the indirect costs. Major depression symptoms can be faked or exaggerated in order to obtain economic compensation from insurance companies. Critically, depression is potentially easily malingered, as the symptoms that characterize this psychiatric disorder are not difficult to emulate. Although some tools to assess malingering of psychiatric conditions are already available, they are principally based on self-reporting and are thus easily faked. In this paper, we propose a new method to automatically detect the simulation of depression, which is based on the analysis of mouse movements while the patient is engaged in a double-choice computerized task, responding to simple and complex questions about depressive symptoms. This tool clearly has a key advantage over the other tools: the kinematic movement is not consciously controllable by the subjects, and thus it is almost impossible to deceive. Two groups of subjects were recruited for the study. The first one, which was used to train different machine-learning algorithms, comprises 60 subjects (20 depressed patients and 40 healthy volunteers); the second one, which was used to test the machine-learning models, comprises 27 subjects (9 depressed patients and 18 healthy volunteers). In both groups, the healthy volunteers were randomly assigned to the liars and truth-tellers group. Machine-learning models were trained on mouse dynamics features, which were collected during the subject response, and on the number of symptoms reported by participants. Statistical results demonstrated that individuals that malingered depression reported a higher number of depressive and non-depressive symptoms than depressed participants, whereas individuals suffering from depression took more time to perform the mouse-based tasks compared to both truth-tellers and liars. Machine-learning models reached a classification accuracy up to 96% in distinguishing liars from depressed patients and truth-tellers. Despite this, the data are not conclusive, as the accuracy of the algorithm has not been compared with the accuracy of the clinicians; this study presents a possible useful method that is worth further investigation.

Background Tardive dyskinesia (TD) is a severe condition that can affect almost 1 out of 4 patients on current or previous antipsychotic treatment, including both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). While two novel vesicular monoamine transporter inhibitors, deutetrabenazine and valbenazine, have shown acute efficacy for TD, the majority of patients do not remit, and TD appears to recur once treatment is withdrawn. Hence, prevention of TD remains a crucial goal. Methods We provide a clinically oriented overview of risk factors for TD, dividing them into patient-, illness- and treatment-related variables, as well as nonmodifiable and modifiable factors. Results Unmodifiable patient-related and illness-related risk factors for TD include older age, female sex, white and African descent, longer illness duration, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related and treatment-related factors include diabetes, smoking, and alcohol and substance abuse, FGA vs SGA treatment, higher cumulative and current antipsychotic dose or antipsychotic plasma levels, early parkinsonian side effects, anticholinergic co-treatment, akathisia, and emergent dyskinesia. Discussion Clinicians using dopamine antagonists need to consider risk factors for TD to minimize TD and its consequences.

Aim The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD). Materials and methods We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed. Results Two acute, 12-week DBRPCTs with deutetrabenazine 12–48 mg/day (n=413) and 4 acute, 4–6-week double-blind trials with valbenazine 12.5–100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =−0.40, 95% confidence interval [CI] =−0.19, −0.62, p

Changes in hippocampal gray matter volumes are proposed to be involved in pathogenesis, course, and treatment response of major depressive disorder. Converging evidence suggests that reduced neurogenesis may occur in treatment-resistant depression (TRD). Vagus nerve stimulation (VNS) is a well-defined, long-term brain stimulation treatment for TRD. However, its in vivo positive effect on hippocampal modulation as mechanism of action has never been investigated before in clinical studies. In this study, we intended to explore hippocampal volumetric changes and clinical antidepressant responses in patients with TRD after 6 and 12 months of treatment with VNS.The TRD outpatients were evaluated for VNS implantation. Right and left hippocampal volumes in 6 TRD patients, who met the criteria for VNS treatment, were measured at baseline before the implantation and after 6 and 12 months. The patients were assessed using Beck Depression Inventory and Hamilton Depression Rating Scale at baseline and at follow-up visits.There was a statistically significant and progressive increase in right and left hippocampal volumes during the follow up (P0.05). Furthermore, patients showed a significant improvement on Hamilton Depression Rating Scale and Beck Depression Inventory scores (P0.05).Our data suggest a VNS modulatory effect on hippocampal plasticity as measured by hippocampal gray volume increase in TRD patients. These preliminary findings indicate the fundamental role of hippocampal remodeling as a marker of response to VNS in TRD.

Catatonia is an independent syndrome that co-occurs with several mental and medical conditions. We performed a systematic literature review in PubMed/Scopus until February 2017 and meta-analyzed studies reporting catatonia prevalence. Across 74 studies (cross-sectional = 32, longitudinal = 26, retrospective = 16) providing data collected from 1935 to 2017 across all continents, mean catatonia prevalence was 9.0% (k = 80, n = 110 764; 95% CI = 6.9-11.7, I2 = 98%, publication bias P < .01), decreasing to 7.8% (k = 19, n = 7612, 95% CI = 7-8.7, I2 = 38.9%) in a subgroup with low heterogeneity. Catatonia prevalence was 23.9% (k = 8, n = 1168, 95% CI = 10-46.9, I2 = 96%) in patients undergoing ECT/having elevated creatinine phosphokinase. Excluding ECT samples, the catatonia prevalence was 8.1% (k = 72, n = 109 606, 95% CI = 6.1-10.5, I2 = 98%, publication bias P < .01), with sensitivity analyses demonstrating that country of study origin (P < .001), treatment setting (P = .003), main underlying condition (P < .001), and sample size (P < .001)moderated catatonia prevalence, being highest in Uganda (48.5%, k = 1) and lowest in Mexico (1.9%, 95% CI = 0.4-8.8, I2 = 67%, k = 2), highest in nonpsychiatric out- or inpatient services (15.8%, 95% CI = 8.1-28.4, I2 = 97%, k = 15)and lowest in psychiatric outpatients services (3.2%, 95% CI = 1.7-6.1, I2 = 50%, k = 3), highest in presence of medical or neurological illness with no comorbid psychiatric condition (20.6%, 95% CI = 11.5-34.2, I2 = 95%, k = 10)and lowest in mixed psychiatric samples (5.7%, 95% CI = 4.2-7.7, I2 =98%, k = 43), highest in studies with sample sizes 1000 (2.3%, 95% CI = 1.3-3.9, I2 = 99%, k = 16). Meta-regression showed that smaller sample size (P < .01) and less major depressive disorder (P = .02) moderated higher catatonia prevalence. Year of data collection did not significantly moderate the results. Results from this first meta-analysis of catatonia frequencies across time and disorders suggest that catatonia is an epidemiologically and clinically relevant condition that occurs throughout several mental and medical conditions, whose prevalence has not decreased over time and does not seem to depend on different rating scales/criteria. However, results were highly heterogeneous, calling for a cautious interpretation. © The Author(s) 2017.

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta-analysis is lacking. We conducted a large-scale meta-analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD-related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4-13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross-sectional studies (odds ratio, OR=1.53, 95% CI: 1.27-1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47-1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21-1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7-5.3) during a median follow-up of 8.4 years (range 1.8-30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60-1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30-1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26-2.14), congestive heart failure (HR=2.10, 95% CI: 1.64-2.70), and CVD-related death (HR=1.85, 95% CI: 1.53-2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD-related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large-scale meta-analysis confirms that SMI patients have significantly increased risk of CVD and CVD-related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention. © 2017 World Psychiatric Association

Patients with severe mental illness (SMI) have been described at higher risk of cardiovascular disease (CVD). The aim of this systematic review and meta-analysis was to quantify prevalence, incidence, cross-sectional association and longitudinal increased risk of coronary heart disease (CHD), stroke, transient ischemic attack and cerebrovascular disease (CBVD), heart failure (HF), peripheral vascular disease (PVD), death due to CVD, and any CVD in patients with SMI. We included 92 studies, with a total population of 3,371,461 patients (BD = 241,226, MDD = 476,102, SCZ = 1,721,586, SMI = 932,547) and 113,925,577 controls. Pooled prevalence of any CVD in SMI was 9.9% (95% CI = 7.4–13.3) (33 studies, 360,144 patients). Compared to controls, after adjusting for a median of 7 confounders, SMI was associated with higher risk of CVD in cross-sectional studies, OR:1.53 (95% CI = 1.27–1.83) (11 studies), with CHD OR: 1.51 (95% CI = 1.47–1.55) (5 studies), with CBVD OR: 1.42 (95% CI = 1.21–1.66) (6 studies), and tended to be associated with HF OR: 1.28 (95% CI = 0.99–1.65) (4 studies). Cumulative incidence was 3.6 CVD events in a median follow-up period of 8.4 years (range: 1.76–30). After considering a median of 6 confounders, SMI was associated with higher longitudinal risk of CVD in longitudinal studies HR: 1.78 (95% CI = 1.6, 1.98) (31 studies), of CHD: HR: 1.54 (95% CI 1.30–1.82) (18 studies), of CBVD HR: 1.64 (95% CI 1.26–2.14) (11 studies), of HF HR:2.10 (95% CI 1.64–2.70) (2 studies), of PVD, unadjusted RR: 3.11 (95% CI 2.46–3.91) (3 studies), of death due to CVD, HR 1.85 (95% CI 1.53–2.24) (16 studies). In this meta-analysis, the association between SMI and CVD has been quantified in a world representative sample; we suggest prevention of CVD should be warranted as standard care in SMI.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Several preclinical studies have demonstrated neuronal effects of glucocorticoids on the hippocampus (HC), a limbic structure with anterior–posterior anatomical and functional segmentation. We propose a volumetric magnetic resonance imaging analysis of hippocampus head (HH), body (HB) and tail (HT) using Cushing's disease (CD) as model, to investigate whether there is a differential sensitivity to glucocorticoid neuronal damage in these segments. We found a significant difference in the HH bilaterally after 12 months from trans-sphenoidal surgical selective resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary micro-adenomas. This pre–post surgery difference could contribute to better understand the pathopysiology of CD as an in vivo model for stress-related hypercortisolemic neuropsychiatric disorders.

Volumetric changes in mood-relevant distributed limbic/paralimbic structures have been reported in the recent literature on the course of mood disorders. Patients with unipolar and bipolar disorders have been found to have smaller hippocampal and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior cingulate cortex (ACC) volumes in female patients with recurrent familial pure depressive disorder (rFPDD). We used semi-automated software for magnetic resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial recurrent major depression (MD) and 15 healthy female subjects. Analysis of covariance, with whole brain volume as covariate, was used to compare volumetric measurements in the two groups. Volumes of the right hippocampal body and tail were significantly smaller in female patients with familial depressive disorder than in healthy subjects. Our data provide evidence of structural lateralized hippocampal body and tail abnormalities in women with familial history and recurrent episodes of depression. Although global reduction of hippocampal volume has been widely reported, data on lateralized regional reductions in familial recurrent depression had not been previously reported. Reduced volume of the right posterior hippocampus could be a structural endophenotype for recurrent depressive disorders in women.

AIMS. To compare, in a "real world" setting, the efficacy and tolerability of two initial duloxetine starting doses: 30 mg once daily (q.d.) for 1 week, followed by escalation to 60 mg q.d. versus 60 mg q.d. without titolation, evaluating expecially the effects on sexual dysfunction.The sample is constituted by outpatients meeting diagnostic criteria for mild-severe (HAMD17or =24 and CGI-Sor =4) Major Depressive Episode as defined by DSM-IV-TR (Diagnostic and Statistic Manual for Mental Disorder, Fourth Edition-Text Revision), based on the Structured Clinical Interview for DSM-IV-TR (Mini International Neuropsychiatric Interview, MINI). The study design planned an initial evaluation and 4 follow-up visits; at each visit the following scales were administered: Hamilton Rating Scale for Depression (HAMD17) and Anxiety (HAMA), Clinical Global Impression Severity Scale (CGI-S) for severity evaluation and Arizona Sexual Experience Scale (ASEX) for sexual disfunction evaluation.Both of the groups showed 90% of response (or = 50% reduction in a patient's HAMD17 total score from baseline) within 2 months of follow-up. 50% of patients receiving a 30 mg q.d. starting dose achieved a HAMD17 total scoreor =7 versus 40% of 60 mg q.d. treating group. None showed relapses during the study. After the first treatment month, the 60 mg q.d. receiving group showed a statistical significative amelioration of sexual function (Mann-Whitney test: p=0,02).Our naturalistic "real world" study results confirm previous duloxetine tolerability and efficacy findings suggesting a 60 mg q.d. after meal duloxetine somministration without titolation.