An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

European Whites May Need Lower Minimum Therapeutic Clozapine Doses Than Those Customarily Proposed.

PURPOSE/BACKGROUND: A nomogram from a British naturalistic study proposed that the clozapine dosing needed to reach a serum concentration of 350 ng/mL ranged from 265 mg/d (female nonsmokers) to 525 mg/d (male smokers). Some European reviews have used these dosing recommendations, which seem greater than what we found in an Italian White sample ranging from 245 mg/d (female nonsmokers) to 299 mg/d (male smokers). Five other published samples of European Whites were added to the Italian sample to estimate clozapine doses recommended for reaching 350 ng/mL. METHODS/PROCEDURES: Average clozapine metabolizers were obtained by eliminating outliers with confounding variables: (1) psychiatric inducers and inhibitors; (2) doses less than 100 mg/d; and (3) when possible, patients with inflammation, obesity, or using oral contraceptives. The study included 1363 average metabolizer European Whites: the Italian sample and 5 new samples. Mean averages that reached serum concentration levels of 350 ng/mL were calculated after stratification by sex and smoking status in each sample. Then, weighted mean averages were obtained by combining the 6 samples. FINDINGS/RESULTS: The estimated weighted mean clozapine dosages ranged from 236 to 368 mg/d (236 mg/d in 218 female nonsmokers, 256 mg/d in 340 male nonsmokers, 357 mg/d in 269 female smokers, and 368 mg/d in 546 male smokers). IMPLICATIONS/CONCLUSIONS: Our recommended dosages are less than those recommended in Europe. Future studies in European Whites need to replicate these recommended doses for average metabolizer patients after sex and smoking stratification and further explore clozapine dosing for those with relevant clinical confounders.

Translation, Cross-Cultural Adaptation, and Validation of the Lee Chronic Graft-versus-Host Disease Symptom Scale in a Brazilian Population.

The Lee Chronic Graft-versus-Host Disease (GVHD) Symptom Scale is a patient-reported instrument developed and validated in English to measure the symptoms and functional impact of cGVHD. This tool has not yet been validated in a Latin American population, however. The Brazil-Seattle Chronic GVHD Consortium conducted a multicenter study at 5 Brazilian institutions to validate the Lee cGVHD Symptom Scale in adults with cGVHD. Study objectives included the translation and validation of the instrument in Brazilian Portuguese and evaluation of the correlation with other quality of life (QoL) tools, including the Medical Outcomes Study Short Form 36 (SF-36) and Functional Assessment of Chronic Illness Therapy with Bone Marrow Transplant subscale (FACT-BMT). Translation and validation were done according to the American Association of Orthopedic Surgeons Outcome Committee guidelines. Spearman's correlation coefficient was used to measure construct validity. Reliability was assessed using Cronbach's α and intraclass correlation coefficients. Between April 2011 and August 2012, 47 patients with cGVHD based on the 2005 National Institutes of Health criteria (29 males [62%], 18 females [38%]; median age, 48 years; range, 23 to 69 years) were enrolled in this study. The reliability of the Lee cGVHD Symptom Scale was adequate (Cronbach's α = 0.62 to 0.83). The correlations between similar domains of the Lee cGVHD Symptom Scale, SF-36, and FACT-BMT were moderate to high. Our data indicate that the Brazilian Portuguese version of the Lee cGVHD Symptom Scale is valid and reliable and can be used in clinical trials of cGVHD in Brazil.

Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder.

Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for generalized anxiety disorder (GAD) were evaluated in a placebo- and lorazepam-controlled, randomized, double-blind, multicentre trial conducted in 16 countries. The study design consisted of two 12-wk treatment periods (periods 1 and 2), each followed by a 1-wk taper and two post-discontinuation assessments, one immediately following the taper and one 1-wk post-taper. Patients were assigned to receive an initially flexible dose of pregabalin 450-600 mg/d, pregabalin 150-300 mg/d, or lorazepam 3-4 mg/d for 6 wk; responders continued fixed-dose therapy for 6 additional weeks. Patients entering period 2 continued on the same fixed dose or switched to placebo. Discontinuation effects were evaluated with the Physician Withdrawal Checklist (PWC) and reported discontinuation-emergent signs and symptoms. Rebound anxiety was measured with the Hamilton Anxiety Rating Scale. GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk. Low levels of discontinuation symptoms were evident in all treatment groups. For patients who received active treatment during both periods, mean (95% confidence interval) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were: pregabalin 450-600 mg/d: 2.8 (1.6-3.9), pregabalin 150-300 mg/d: 1.7 (0.7-2.8), lorazepam 3-4 mg/d: 2.2 (1.0-3.5). Rates of rebound anxiety were also low at both 12 and 24 wk (0-6%). This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment.

Effects of the economic crisis on demand due to mental disorders in Asturias: data from the Asturias Cumulative Psychiatric Case Register (2000-2010).

INTRODUCTION: The economic crisis has negative effects on the population's physical and mental health. Our objective has been to study the association between socioeconomic status and number of people demanding mental health services. METHODS: We performed a correlation analysis of administrative morbidity data (incidence and prevalence) of mental illness (obtained from the Asturias Cumulative Psychiatric Case Register) and three economic indicators (unemployment, consumer price index and gross domestic product). RESULTS: The increase in the unemployment rate is associated with a clear decrease in both new and prevalent mental health demand. CPI has a minor weak positive correlation with the administrative incidence of some mental disorders (Neurotic disorders, Schizophrenia and addictions). GDP does not show a significant correlation with the administrative incidence and it is strongly associated with an increased administrative prevalence that is more intense in the case of alcoholism, neurotic disorders, mental retardation and Z codes (ICD-10). CONCLUSION: The variation of the socioeconomic indicated observed in the economic crisis period in Asturias was not associated with increased care demand for any mental disorders. There is a negative correlation of unemployment rate with care demand.

Systematic depression screening in high-risk patients attending primary care: a pragmatic cluster-randomized trial.

BACKGROUND: Systematic screening for depression in high-risk patients is recommended but remains controversial. The aim of this study was to assess the effectiveness of such screening in everyday clinical practice on depression recognition. METHODS: A pragmatic, cluster randomized, controlled study that randomized primary care physicians (PCPs) in Spain either to an intervention or control group. The intervention group (35-PCPs) received training in depression screening and used depression screening routinely for at least 6 months. The control group (34-PCPs) managed depression in their usual manner. Adherence to (1-6; never-very frequently), feasibility (1-4; unfeasible-very feasible), and acceptance (1-5; very poor-very good) of the screening were evaluated. Underrecognition (primary outcome) and undertreatment rates of major depressive disorder (MDD) in the two groups were compared 6 months after randomization in a random sample of 3737 patients assigned to these PCPs using logistic regression adjusting for the clustering effect. RESULTS: No significant differences were found for recognition rates (58.0% vs. 48.1% intervention vs. control; OR [95%CI] 1.40 [0.73-2.68], p = 0.309). The undertreatment rate did not differ significantly either (p = 0.390). The mean adherence to depression screening was 4.4 ± 1.0 ('occasionally'), the mean feasibility was 3.1 ± 0.5 ('moderately feasible'), and the mean acceptance was 4.2 ± 0.6 ('good'). CONCLUSIONS: This research was not able to show effectiveness of the systematic screening for MDD in high-risk patients on depression recognition in primary care. The poor adherence to screening implementation could partially explain the results. These reflect the difficulties of putting into practice the clinical guidelines usually based on interventional research. TRIAL REGISTRATION: Clinicaltrials.gov NCT01662817.

Bed-material entrainment in a mountain river affected by hydropeaking.

Hydropeaking, by artificially generated flow peaks, influences hydro-sedimentary dynamics on rivers and, consequently, affects bed material entrainment and transport. This study examines the onset of motion of sediment particles in four sections of a Pyrenean gravel-to-cobble bed river exposed to frequent hydropeaking (once per day, on average). Five criteria of particle entrainment have been used to assess the prediction of the initiation of grain motion at-a-section scale. Theoretical entrainment conditions were validated using real observations of mobility by means of tracers. It was found that the maximum flow discharged by the hydropower plant mostly affects the furthest downstream section, located almost 17 km downstream, in which the finer fractions of the bed are entrained. The mobile grain sizes include up to coarse gravels (≈ 30 mm). Differences in sediment supply (imposed by tributaries), the value of the bed slope and the structure of the coarse surface layer decisively control the downstream variability of incipient particle motion between sections. Results from a 17 km study segment indicated that hydropeaking generate partial transport, that is, a partially size-selective transport that occurs downstream from the hydropower plant and winnows the sand and small gravel further downstream, increasing armouring and depleting fine sediments.

Quality of life in depressed women over 40 years old.

OBJECTIVES: This study aims to determine quality of life and satisfaction in depressed Spanish women over 40 years old in the outpatient psychiatry setting. Secondarily, the association between several characteristics of depressed patients and quality of life was assessed. MATERIAL AND METHODS: Cross-sectional, descriptive study, carried out in the Spanish psychiatry setting in 2008. A total of 365 Spanish psychiatrists participated. 1069 patients older than 18 years old signed the informed consent. Depressive symptoms were assessed using the 17 Item Hamilton for Depression Rating Scale (HAM-D17). The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale assessed the patient's satisfaction and life enjoyment. RESULTS: Were included a total of 942 patients with the following characteristics: mean age of 52.46 years, medical comorbidity in 62.9%, and a history of psychiatric disorders in 79.6%. HAM-D17 mean score of 21.39. According to the Q-LES-Q questionnaire, Global satisfaction mean score was of 35.2%, the highest mean scores were achieved in the treatment satisfaction and the lowest mean scores in free time activities. The quality of life was influenced by the intensity of depressive symptoms and physical comorbidity. CONCLUSION: The study results show an impairment of quality of life in depressed women attending outpatient psychiatric centers. This decrease in the quality of life is associated with depressive symptoms and medical comorbidity.

[Native and non-native antigen to determine the seroprevalence of Trypanosoma cruzi in pregnant women from the state of Morelos, Mexico]. / Antígeno nativo y no nativo para determinar la seroprevalencia de Trypanosoma cruzi en mujeres embarazadas en el estado de Morelos, México.

BACKGROUND: Chagas disease is a globally important chronic systemic parasitic infection caused by Trypanosoma cruzi. AIM: To determine the prevalence of antibodies against T cruzi in pregnant women from the state of Morelos, México. METHODS: 1,620 sera from pregnant women were analyzed using two serological tests: ELISAc (native crude antigen) and ELISAr (recombinant, non-native antigen). Reactive samples were subsequently analyzed by indirect hemagglutination (IHA). Two detection approaches were used, in parallel (reactive samples by any method are positive) and serial (samples confirmed by IHA are positive). Sociodemographic and health factors associated with the presence of antibodies against T cruzi were evaluated using 95% odds ratios. RESULTS: A seroprevalence of 4.87% was obtained with parallel diagnosis and 0.43% in series. From the parallel results, the women who were attended at the general hospitals of Tetecala and Jojutla had respectively 2.2 and 2.0 times greater chance of presenting antibodies against T cruzi compared to the women who were attended at the General Hospital of Cuautla. CONCLUSION: The prevalence of antibodies against T cruzi in pregnant women from the state of Morelos fluctuated between 0.43 and 4.87%, depending on the antigen and the approach used. It is necessary to continue with the surveillance of the seroprevalence of antibodies against T cruzi in pregnant women from the state of Morelos, Mexico, using the techniques with the highest sensitivity and specificity available.

Does COVID-19 psychological fatigue exist? Results of three online cross-sectional studies conducted in Spain from April 2020 to March 2021.

Background: A previously published meta-analysis found that about one-third of the general population experienced some mental health problem during the early phase of the COVID-19 pandemic, potentially leading to a late mental health crisis. We aimed to describe the acute, short-term, and long-term effects of the COVID-19 pandemic on mental health. Methods: A one-year online survey (S) was conducted in Spain (April 2020 - March 2021). We recruited 18 180 subjects using a virtual respondent-driven snowball sampling method (S1 April 2020, n = 6108; S2 October-November 2020, n = 6418; S3 March 2021, n = 5654). Participants completed the Spanish Depression, Anxiety, and Stress Scale (DASS-21). Results: Overall, our results suggest a progressive increase in the prevalence of anxiety and stress throughout the pandemic waves and relative stability of depression. Women had a greater probability of having depression, anxiety, or stress than men in each survey (P < 0.001). The youngest group (aged 18-24) reported a higher probability (P < 0.05) of having depression, anxiety, or stress than the older groups in S1 and S2. Middle-aged people (25-59) had a greater probability of being a case in the DASS-21 scales than the oldest group (60+), except for depression in men (P = 0.179). In S3, the trend changed: the youngest group showed a decrease in depression and stress while the oldest group showed a dramatic increase (anxiety: men = 664.5%, women = 273.52%; stress: men = 786%, women = 431.37%). Conclusions: It is plausible to conclude that COVID-19 psychological fatigue exists, especially in middle-aged and older adults. Strategies to assist people who have fewer coping skills should be implemented in the near future.

Responses of resources and consumers to experimental flow pulses in a temporary Mediterranean stream.

Determining the resistance and resilience of resources and benthic invertebrates connected to instream refuges and species re-colonization in post-flood periods may help to elucidate mechanisms behind community recovery. This experiment simulated flow pulses in a small temporary stream in an extremely wet year, using upstream control and downstream flooded reaches at three sites in order to assess community resistance and resilience (benthos and drift), and analyse resources (periphyton and benthic organic matter) and invertebrates at pre- and post-flood time periods. The hyporheos was sampled in order to explore species exchanges with benthos. Fewer resources and benthic invertebrates at the beginning of the experiment were found than in previous studies when base flow conditions prevailed. Resource stocks and benthic invertebrates showed high resistance to the flow pulse. Interestingly, there was low resilience of benthic organic matter to natural seasonal flooding. Chlorophyll a did not recover after experimental floods; instead, it was reduced after floods, despite the more benign flow conditions and non-limiting irradiance levels, pointing to top-down control by consumers. Additionally, the experimental flood significantly disturbed only the invertebrate composition in the groundwater-fed stream, which was inhabited by the fewest adapted-to-flood-disturbances macroinvertebrates. Despite the low resilience observed, richness and densities of benthos increased during the study, evidencing progressive colonization. Around 50-60% of macroinvertebrates were present in both benthos and hyporheos. Richness increased after flooding, suggesting that the hyporheic zone could be the main source of colonizers. Three species traits characterized the hyporheos: small size, cocoons and feeders of microorganisms within the fine sediment matrix. The main results indicate that longer-than-normal flood periods in early spring may constrain invertebrate succession before the next summer drought in temporary streams. This study underscores the importance of hyporheic fauna as a significance source of colonizers, highlighting the importance of connectivity to the groundwater.

Screening for anxiety and depression in Primary Care: Utility of 2 brief scales adapted to the ICD-11-PC.

INTRODUCTION: The World Health Organization has developed a new classification of mental disorders in Primary Health Care (PHC), the ICD-11-PHC, in which there are changes in the diagnostic criteria of anxiety and depression disorder. In addition, 2 screening instruments have been developed for the detection of anxious and depressive symptoms according to the criteria of the new classification. OBJECTIVES: To evaluate the capacity of the Spanish version of the 2 brief scales Dep5 and Anx5 to identify cases of depression and anxiety in PHC in Spain. METHOD: A cross-sectional study conducted by 37 PHC physicians who selected 284 patients with suspected emotional distress. This sample was administered the screening scales (Anx5 and Dep5) and a diagnostic instrument (Clinical Interview Schedule-Revised) contemplating the new ICD-11 criteria as used as gold standard. RESULTS: The Anx5, using a cut-off point of 3, showed a sensitivity of 0.75 and specificity of 0.53. Using a cut-off point of 4, the Dep5 showed a sensitivity of 0.48 and a specificity of 0.8. The 2 scales together, with a cut-off point of 3 for each, classified correctly 73,57% as cases or non-cases. The diagnosis most frequently observed was anxious depression. CONCLUSIONS: The screening scales for anxious and depressive symptoms (Anx5 and Dep5) are simple and easy-to-use instruments for assessing anxious and depressive symptoms in PHC. The reliability and validity data of each of the scales separately are limited but the figures improve when they are used together.

Comparative study of the environmental footprints of marinas on European Islands.

Ports have been key elements in Europe's economic development. This situation is even more relevant on islands, which are highly dependent on the maritime sector. Consequently, over the years, ports with diverse functionalities have been established both in mainland Europe and on its outlying islands. This article discusses the environmental impact of leisure marinas on European islands, especially as they are closely linked to economic development through tourism. The aim is to study the environmental impact of these infrastructures by determining the carbon and water footprints of marinas on European islands in the Atlantic and the Mediterranean. The results obtained enable the authors to make recommendations in order to reduce the overall environmental footprint of marinas on islands, considering that these territories are much more vulnerable to climate change than mainland locations in Europe.

Downstream changes of particle entrainment in a hydropeaked river.

Hydropeaking, through artificially generated flow peaks, affects hydro-sedimentary dynamics on rivers. The frequency and magnitude of such artificial flow pulses impact sedimentary process and, inevitably, affects bed-material entrainment. This study analyses the entrainment of particles in six sections of a Pyrenean river under frequent hydropeaking. Three equations of particle entrainment with contrasting behaviours, validated for particle mobility from tracer data, have been used to predict the initiation of motion in each section. Results show that the peak discharge generated by the hydropower station mostly affects the section immediately downstream from the hydropower plant, where the finer fractions of the bed are mobilised. The mobile grain sizes include fine to medium gravels (< 20mm). Channel geometry and higher slopes also have an effect on particle entrainment. Entrainment of the finer size fractions of the bed is termed partial transport, i.e. a partially size-selective transport that occurs downstream from the hydropower station and winnows the sand and small gravel further downstream.

Screening for anxiety and depression in Primary Care: Utility of 2 brief scales adapted to the ICD-11-PC. / Detección de ansiedad y depresión en Atención Primaria: utilidad de 2 escalas breves adaptadas a los nuevos criterios CIE-11-AP.

INTRODUCTION: The World Health Organization has developed a new classification of mental disorders in Primary Health Care (PHC), the ICD-11-PHC, in which there are changes in the diagnostic criteria of anxiety and depression disorder. In addition, 2 screening instruments have been developed for the detection of anxious and depressive symptoms according to the criteria of the new classification. OBJECTIVES: To evaluate the capacity of the Spanish version of the 2 brief scales Dep5 and Anx5 to identify cases of depression and anxiety in PHC in Spain. METHOD: A cross-sectional study conducted by 37 PHC physicians who selected 284 patients with suspected emotional distress. This sample was administered the screening scales (Anx5 and Dep5) and a diagnostic instrument (Clinical Interview Schedule-Revised) contemplating the new ICD-11 criteria as used as gold standard. RESULTS: The Anx5, using a cut-off point of 3, showed a sensitivity of 0.75 and specificity of 0.53. Using a cut-off point of 4, the Dep5 showed a sensitivity of 0.48 and a specificity of 0.8. The 2 scales together, with a cut-off point of 3 for each, classified correctly 73,57% as cases or non-cases. The diagnosis most frequently observed was anxious depression. CONCLUSIONS: The screening scales for anxious and depressive symptoms (Anx5 and Dep5) are simple and easy-to-use instruments for assessing anxious and depressive symptoms in PHC. The reliability and validity data of each of the scales separately are limited but the figures improve when they are used together.

Effectiveness of a psychoeducational intervention program in the reduction of caregiver burden in Alzheimer's disease patients' caregivers.

OBJECTIVES: Caregivers of patients with Alzheimer's disease (AD) experience physical and psychological stress due to the caring experience. This study evaluated the benefits of a Psychoeducational Intervention Program (PIP) on caregiver burden in southern Europe. METHODS: A multicentre, prospective, randomised study was conducted. One hundred and fifteen caregivers of patients with clinical diagnosis of AD (DSM-IV-TR criteria, mini-mental score = 10-26) and functional impairment (Lawton and Brody Scale and Katz Index) were recruited. Caregivers were randomised to receive either PIP (IG: intervention group, n = 60) or standard care (CG: control group, n = 55). PIP consisted of eight individual sessions over 4 months for teaching strategies for confronting problems of AD patient care. Caregivers' stress, quality of life and perceived health were measured using validated scales (Zarit, SF-36, GHQ-28, respectively) at baseline and after 4 and 10-months follow-up. RESULTS: Mean change in caregiver burden (Zarit baseline-Zarit final scores) was statistically significant (p = 0.0083) showing an improvement in the IG (-8.09 points) and a worsening in the CG (2.08 points). The IG showed significant improvements in all the well-being perception areas measured by the SF-36 and a significantly lower score in the GHQ-28 (p = 0.0004). 97.7% of caregivers and 88.6% of therapists considered PIP 'useful/very useful' at 4 months (the end of PIP) whereas at 10 months the estimates were 93.2% and 86.3%, respectively. CONCLUSIONS: Psychosocial training of caregivers can minimise caregiver distress and help them to develop problem-solving strategies. A PIP improves quality of life and the perceived health of caregivers of patients with AD.

Can interleukin-2 and interleukin-1ß be specific biomarkers of negative symptoms in schizophrenia? / ¿Pueden ser la interleucina-2 y la interleucina-1ß biomarcadores específicos de la sintomatología negativa en la esquizofrenia?

INTRODUCTION: Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-α, interleukin (IL)-6, IL-2, IL-1ß, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. METHODS: We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. RESULTS: Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1ß concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. CONCLUSIONS: Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1ß is not specific to this dimension as it also predicts severity of general and global symptomatology.

Elevated C-reactive protein as a predictor of a random one-year clinical course in the first ten years of schizophrenia.

We investigate whether C-reactive protein (CRP) levels could predict the clinical course of patients with schizophrenia in a prospective study of 50 stable outpatients during a random 1-year period within the first 10 years of illness. Positive, negative, depressive, and cognitive symptoms were evaluated. Patients with low-grade inflammation (CRP = 3-10 mg/L; 28%) at baseline showed significant worsening of PANSS-positive and general psychopathology at 1-year follow-up compared with those with CRP ≤ 3 mg/L. Elevated CRP may be a biomarker of poor 1-year clinical course in patients with schizophrenia.