BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype.

Fibromuscular dysplasia of cervicocephalic arteries: Prevalence of multisite involvement and prognosis.

BACKGROUND: Fibromuscular dysplasia (FMD) is a noninflammatory nonatherosclerotic disease of small- to medium-sized arteries. The frequency of multisite involvement and its influence on prognosis has not been systematically assessed in patients with cervicocephalic FMD, and little is known about their mid-term clinical and arterial prognosis. The aim of our study was to assess the prevalence of renal involvement and clinical and arterial prognosis in patients with cervicocephalic FMD. METHODS: We reviewed clinical and radiological data of consecutive patients with a diagnosis of cervicocephalic FMD, admitted to our hospital between January 2000 and March 2010. Patients were identified retrospectively until December 2008, and prospectively from January 2009. For each cervical and intracranial artery, we recorded the presence and type (unifocal or multifocal) of FMD. We classified each FMD-related stenosis into four categories:<50%, 50-80%,>80% and occlusion. During the first six months of 2012, patients were scheduled for follow-up visit, including cervicocephalic follow-up imaging, and renal artery imaging, if not already available. On follow-up imaging, FMD-related stenosis was classified according to the same method used at baseline. Renal artery FMD was defined as the presence of the typical string of beads appearance, or as the presence of a unique stenosis of renal artery. Primary endpoints were stroke (ischemic or hemorrhagic), death, and progression of FMD lesions, defined by any increase in category of stenosis on follow-up imaging. RESULTS: Out of the 36 patients included (32 women), all with carotid artery involvement and 17 with associated vertebral artery involvement, 28 (78%) had ischemic symptoms and/or cervical artery dissection at the time of the diagnosis of FMD. Among the 30 patients who had renal artery imaging, 13 (43%) had renal FMD. Patients with renal artery disease did not differ from those without renal artery disease. After a median follow-up of 3.5 years, three patients had four strokes, one recurrent cervical dissection, one brain hemorrhage, and one fatal cardiac arrhythmia. Among the 31 patients who had follow-up imaging, two showed progression of cervicocephalic FMD (occlusion of carotid artery). Patients with renal involvement showed a non-significant trend toward a higher rate of stroke (P=0.17). CONCLUSIONS: In patients with cervicocephalic FMD, renal involvement is common. The risk of stroke, death or FMD progression was high in our cohort, suggesting that prognosis may not be as good as expected. This underlines the need for larger prospective studies to define the best treatment options.

Ethiopathogenesis of depressive disorders.

Etiology of depressive disorders is still unknown. Several factors are involved in its pathophysiology such as neurotransmitters and neuroendocrine alterations, genetics, life events and their appraisal. Some of these components are strictly linked. Subjects with a family member affected by mood disorders are more prone to suffer from depressive disorders. It is also true that receiving feedbacks of indifference or neglect during childhood from one parent who suffer from depression may represent a factor of vulnerability. Indeed, reaction to a specific negative event may determine an increased allostasis which lead to a depressive episode. Thus, a psychological cause does not exclude a neurobiological cascade. Whereas in other cases recurrent depressive episodes appear in absence of any negative life event. This review provides a set of data regarding the current etiopathogenesis models of depression, with a particular attention to the neurobiological correlates and vulnerability factors.

Binding energy determination in a π-stacked aromatic cluster: the anisole dimer.

The binding energies of the neutral and positively charged anisole dimer have been determined in molecular beam-laser spectroscopy experiments. This is the first report on the direct experimental determination of the binding energy for an aromatic cluster in π stacked configuration. The anisole dimer is formed by two anisole molecules superimposed in a planar arrangement and it has been proposed as a model system in which the π-stacking interaction, among other intermolecular forces, plays a relevant role. Its binding energy has been determined thanks to both velocity mapping ion/electron imaging experiments and previous spectroscopic information. The binding energy amounts to 3926(250) cm(-1) in the ground state and 4144(250) cm(-1) in the S2 (first spectroscopically accessible) electronic excited state; its value for the positively charged dimer ion increases to 6147(250) cm(-1). These values are quite higher with respect to the results of previous DFT calculations.

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage. OBJECTIVES: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. CONCLUSIONS: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

Laparoscopic ventral hernia repair: does IPOM plus allow to increase the indications in larger defects?

PURPOSE: The laparoscopic ventral hernia repair (LVHR) may have a limit of effectiveness, especially in defects greater than 80 cm2, with a higher recurrence rate which contraindicates this technique. The purpose of this study is to analyze the indication of LVHR determining and comparing the recurrence rate according to defect size in two series. METHODS: We analyzed all patients who underwent LVHR between 2007 and 2017. Patients were divided according to the ring size: < o ≥ 80 cm2 into group one (G1) and group two (G2) respectively. In both groups, all three techniques were used: intraperitoneal onlay mesh (IPOM), IPOM with closure of the defect (IPOM plus), and IPOM plus + anterior videoscopic component separation (AVCS). RESULTS: A total of 258 patients underwent LVHR. Mean recurrence rate was 13% in G1 and 24% in G2. A statistically significant difference was found when comparing the IPOM technique among both groups, with a higher recurrence rate when ring size was ≥ 80 cm2 (p < 0.5). However, when comparing recurrence rate in IPOM plus and IPOM plus + AVCS between both groups, no significant differences were observed, yielding a p of 0.51 and 0.63, respectively. CONCLUSION: The IPOM technique has shown a limit of effectiveness in large ventral hernia defects. The combination of techniques (ring closure and AVCS) may be useful to expand the indication for this surgery to larger defects and to reduce the recurrence rate. Prospective randomized studies are required to confirm this trend.

Frailty in Caregivers and Its Relationship with Psychological Stress and Resilience: A Cross-SectionalStudy Based on the Deficit Accumulation Model.

BACKGROUND: Studies increasingly suggest that chronic exposure to psychological stress can lead to health deterioration and accelerated ageing, thus possibly contributing to the development of frailty. Recent approaches based on the deficit accumulation model measure frailty on a continuous grading through the "Frailty Index" (FI), i.e. a macroscopic indicator of biological senescence and functional status. OBJECTIVES: The study aimed at testing the relationship of FI with caregiving, psychological stress, and psychological resilience. DESIGN: Cross-sectional study, with case-control and correlational analyses. PARTICIPANTS: Caregivers of patients with dementia (n=64), i.e. individuals a priori considered to be exposed to prolonged psychosocial stressors, and matched controls (n=64) were enrolled. MEASUREMENTS: The two groups were compared using a 38-item FI condensing biological, clinical, and functional assessments. Within caregivers, the association of FI with Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS) was tested. RESULTS: Caregivers had higher FI than controls (F=8.308, p=0.005). FI was associated directly with PSS (r=0.660, p<0.001) and inversely with BRS (r=-0.637, p<0.001). Findings remained significant after adjusting for certain confounding variables, after excluding from the FI the conditions directly related to psychological stress, and when the analyses were performed separately among participants older and younger than 65 years. CONCLUSIONS: The results provide insight on the relationship of frailty with caregiving, psychological stress, and resilience, with potential implications for the clinical management of individuals exposed to chronic emotional strain.

Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis).

Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a rare condition whose pathogenesis is unknown, though autoimmune-mediated mechanisms are thought to be involved. The prevalent neurological manifestations of this disorder are epileptic seizures and psychocognitive disorders associated with EEG alterations. High anti-thyroid antibody titers (particularly in cerebrospinal fluid) and the effectiveness of steroid therapy are usually considered to be crucial elements in the diagnostic process. We describe a 19-year-old female patient who had been referred to the psychiatric unit because of behavioral disorders characterized predominantly by delirium with sexual content. She developed recurrent focal seizures characterized by atypical ictal semiology (repetitive forceful yawning) and a rare EEG pattern (recurrent seizures arising from the left temporal region without evident "encephalopathic" activity). The presence of anti-thyroperoxidase antibodies in her cerebrospinal fluid and a good response to steroids confirmed the diagnosis of HE. The atypical presentation in the case we describe appears to widen the electroclinical spectrum of HE and highlights its importance for differential diagnosis purposes in the neuropsychiatric setting.

Combining robotics with enhanced serotonin-driven cortical plasticity improves post-stroke motor recovery.

Despite recent progresses in robotic rehabilitation technologies, their efficacy for post-stroke motor recovery is still limited. Such limitations might stem from the insufficient enhancement of plasticity mechanisms, crucial for functional recovery. Here, we designed a clinically relevant strategy that combines robotic rehabilitation with chemogenetic stimulation of serotonin release to boost plasticity. These two approaches acted synergistically to enhance post-stroke motor performance. Indeed, mice treated with our combined therapy showed substantial functional gains that persisted beyond the treatment period and generalized to non-trained tasks. Motor recovery was associated with a reduction in electrophysiological and neuroanatomical markers of GABAergic neurotransmission, suggesting disinhibition in perilesional areas. To unveil the translational potentialities of our approach, we specifically targeted the serotonin 1A receptor by delivering Buspirone, a clinically approved drug, in stroke mice undergoing robotic rehabilitation. Administration of Buspirone restored motor impairments similarly to what observed with chemogenetic stimulation, showing the immediate translational potential of this combined approach to significantly improve motor recovery after stroke.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

The gas phase anisole dimer: a combined high-resolution spectroscopy and computational study of a stacked molecular system.

The gas phase structures of anisole dimer in the ground and first singlet electronic excited states have been characterized by a combined experimental and computational study. The dimer, formed in a molecular beam, has been studied by resonance-enhanced multiphoton ionization and high-resolution laser-induced fluorescence techniques. The assignment of the rotational fine structure of the S(1) <-- S(0) electronic transition origin has provided important structural information on the parallel orientation of aromatic rings of anisole moieties. By comparison with the DFT/TD-DFT computational results, it has been possible to infer the detailed equilibrium structure of the complex. The analysis of the equilibrium structure and interaction energy confirms that the anisole dimer is stabilized by dispersive interaction in the gas phase. This is, to the best of our knowledge, the first detailed work (reporting both theoretical and high-resolution experimental data) on an isolated cluster in the pi-stacking configuration.

Influence of cognitive impairment on the institutionalisation rate 3 years after a stroke.

BACKGROUND AND PURPOSE: Pre-existing cognitive decline and new-onset dementia are common in patients with stroke, but their influence on institutionalisation rates is unknown. OBJECTIVE: To evaluate the influence of cognitive impairment on the institutionalisation rate 3 years after a stroke. DESIGN: (1) The previous cognitive state of 192 consecutive patients with stroke living at home before the stroke (with the Informant Questionnaire on COgnitive Decline in the Elderly (IQCODE)), (2) new-onset dementia occurring within 3 years and (3) institutionalisation rates within 3 years in the 165 patients who were discharged alive after the acute stage were prospectively evaluated. RESULTS: Independent predictors of institutionalisation over a 3-year period that were available at admission were age (adjusted odds ratio (adjOR) for 1-year increase = 1.08; 95% confidence interval (CI) 1.03 to 1.15), severity of the neurological deficit (adjOR for 1-point increase in Orgogozo score = 0.97; 95% CI 0.96 to 0.99) and severity of cognitive impairment (adjOR for 1-point increase in IQCODE score = 1.03; 95% CI 1 to 1.06). Factors associated with institutionalisation at 3 years that were present at admission or occurred during the follow-up were age (adjOR for 1-year increase = 1.17; 95% CI 1.07 to 1.27) and any (pre-existing or new) dementia (adjOR = 5.85; 95% CI 1.59 to 21.59), but not the severity of the deficit of the neurological deficit. CONCLUSION: Age and cognitive impairment are more important predictors of institutionalisation 3 years after a stroke than the severity of the physical disability.

Latin America: the next region for haematopoietic transplant progress.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

Cure of multiple myeloma -- more hype, less reality.

Randomized studies have firmly established the role of autologous transplant as initial therapy in multiple myeloma (MM). Indeed, MM has emerged as the commonest indication for autologous SCT in North America. The conceptual basis for high-dose therapy is the goal of complete remission (CR) through steep reduction in tumor burden affected by single and tandem transplants. Careful analysis of the data challenges the notion of CR as a surrogate to success. Intrinsically aggressive MM, defined by known unfavorable biologic risk factors, overrides the benefit of CR. In contrast, subgroups of patients with favorable biological risk factors may achieve prolonged survival, often without ever achieving CR. Unfortunately, even with tandem transplants, there is no plateau in survival curves. To this end, sequential autologous followed by nonmyeloablative allotransplants are a novel attempt at 'curing' myeloma, but the results thus far have failed to show a definite plateau in survival. Given the improvements in supportive care and concomitant reduction in transplant-related mortality, conventional myeloablative allogeneic transplants need to be re-examined as an option in high-risk aggressive myeloma. At the same time, novel antimyeloma therapies, newer risk stratification and staging tools are transforming the treatment algorithm. We examine the changing role of transplantation in myeloma in the context of novel drug therapy, biologic risk stratification and improving supportive care while arguing that the current 'one size fits all' transplant approaches are far from a cure.

The use of town refuse ash in urban agriculture around Jos, Nigeria: health and environmental risks.

This paper reports on a study that examines the health and environmental risks of using town refuse ash in urban vegetable production in Jos, Nigeria, in terms of heavy metal accumulation in the food chain. Soil and crop samples, collected from five study farms, and samples of the river water used for irrigation, were analysed for seven heavy metals Fe, Mn, Zn, Cu, Ni, Cd and Pb. On the basis of the field data the paper discusses: (1) the potential soil deficiencies and toxicities; (2) the probable links between soil heavy metal levels and fertilisation practices; (3) the heavy metal concentrations in crop tissue in relation to crop growth and human health. The findings suggest that soil concentrations of the seven metals fall within 'typical' soil levels, and that there should not be any problems of either toxicities or deficiencies for crop growth. There was evidence of slight accumulation of Zn, Cu and Cd on some of the farms with a history of town refuse ash use. However, in all farms lettuce crops contained very large concentrations of Fe, and Pb concentrations that were 20 to 40 times higher than the WHO/FAO maximum recommended level in leafy vegetables for human consumption. The Cd content of carrot tissue was 10 times higher than the WHO/FAO recommended limit. The relatively small number of soil and crop samples precluded any formal attempt at correlating the concentrations of heavy metals found in the vegetable crops with the farm levels. Nevertheless, the data suggested that these were not linked. The paper goes on to consider various potential sources of the metals found in the crops, including irrigation water, town refuse ash and air-borne dust, and discusses additional health and environmental risks pertaining to the use of town refuse ash. Undoubtedly, the heavy Pb and Cd contamination of certain crops indicates the urgent need for future studies to ascertain the precise source of these metals, and although the practice of using town refuse ash does not appear to have resulted in large-scale contamination of soil in the farming area, there are a number of unsafe practices associated with it that call for the identification of strategies for the safe utilisation of urban waste in Jos.

Haematopoietic cell transplants in Latin America.

Haematopoietic cell transplants are done by more than 1500 transplant centres in 75 countries, mostly for life-threatening haematological disorders. However, transplant technology and access are not uniformly distributed worldwide. Most transplants are done predominately in Europe, North America and some Asian countries. We review transplant activity in Latin America, a geographic region with a population of >600 million persons living in countries with diverse economic and social development levels. These data indicate a 20-40-fold lower frequency of transplants in Latin America compared with Europe and North America. We show that although economics, infrastructure and expertise are important limitations, other variables also operate. Changes in several of these variables may substantially increase transplant activity in Latin America.

DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation.

Parainfluenza virus (PIV) may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.

Endothelial precursors and mature endothelial cells are increased in the peripheral blood of myelodysplastic syndromes.

Increased angiogenesis has been demonstrated to be a significant prognostic factor in many solid tumors. In the oncohematological setting, it has been associated with myelodysplastic syndromes (MDS), chronic myeloid leukemia, acute lymphoid, and myeloid leukemias. Recently, increased circulating endothelial cells (CECs) have been associated with breast cancer and non-Hodgkin lymphoma (NHL). Based on these premises we analysed total and activated CECs, and endothelial precursors (CEPs) in 50 MDS patients and 20 healthy donors. CECs and CEPs were quantified by flow cytometry. CEC levels were compared with bone marrow (BM) microvessel density (MVD). In addition, some angiogenic factors, namely vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble VEGF-Receptor2 (VEGFR2), were tested in the sera from 25 MDS patients. Total, activated CECs and CEPs were significantly increased in MDS when compared to control group (p<0.0001); whereas in the MDS cases no association was found with French--American--British (FAB), International Prognostic Scoring System (IPSS) subtypes or survival. Patients with higher CECs also showed higher MVD. Among the cytokines analysed, sVEGFR2 was significantly higher in the lower IPSS risk classes, while the levels of bFGF directly correlated with total and activated CECs. Taken together these data strengthen the hypothesis of a possible role of angiogenesis in MDS pathogenesis.

Dimensional psychopathology of depression: detection of an 'activation' dimension in unipolar depressed outpatients.

BACKGROUND: Despite the high prevalence of bipolar spectrum disorders, most instruments currently available for the assessment of depression do not explore symptoms of 'activation' such as anger, irritability, aggressiveness, hostility, and psychomotor activation. METHODS: Two samples of adults with unipolar depression were studied. They had no comorbid DSM-IV disorder, and they were free from antidepressant drugs. The first sample (n = 380) was assessed with the SVARAD, a validated scale for the rapid assessment of the main psychopathological dimensions. The second sample (n = 143) was assessed with the MMPI-2. Factor analysis was performed on SVARAD items and MMPI-2 clinical scales. RESULTS: In both samples, we obtained a three-factor solution with factors interpreted as a depressive dimension, an anxious dimension, and an activation dimension. The latter dimension appeared to be clinically relevant in 20-27% of patients. LIMITATIONS: The presence of a comorbid disorder may have been missed in some cases. Also, some bipolar II patients might have been misdiagnosed as unipolar and included in the study. Further, our findings apply only to a selected psychiatric population, and it should be tested whether they generalize to other settings of care and other countries. CONCLUSIONS: Our results suggest that depressive mixed states are not rare even in patients diagnosed as unipolar, and that some unipolar patients might actually be 'pseudounipolar' and belong to the bipolar spectrum. More in general, our findings suggest that some depressed patients have prominent symptoms of activation that can easily go unnoticed using instruments that do not explore such symptoms. Detecting these symptoms has important treatment implications.