Aggressiveness and violence in psychiatric patients: a clinical or social paradigm?

OBJECTIVE: Psychiatric disorders are often considered the leading cause of violence. This may be due to a stereotype created by media and general opinion. METHOD: The Modified Overt Aggression Scale (MOAS) was used to evaluate the severity of aggressive and violent behaviors in 400 patients who attended a post-acute psychiatric service in Milan from 2014 to 2016 and suffered from different psychiatric disorders. The psychopathological clinical picture was evaluated by Clinical Global Impression (CGI). The study also assessed the possible correlation between epidemiologic and sociodemographic factors, clinical variables, and aggression and violence. RESULTS: Of the total number of subjects, 21.50% showed a MOAS score >0, 11.50% presented mild aggression (0-10 MOAS weighted score), 9% moderate aggression (11-20), and 1% severe aggression (MOAS >20). With respect to violent behaviors, 16% of patients showed a score >0 in one MOAS subscale other than verbal aggression according to violence definition. The severity of clinical picture seemed to be related to higher weighted MOAS score. Multivariate testing of different sociodemographic and clinical variables showed that violence was related to unemployment status, and significantly correlated to compulsory admission (TSO), suicide attempts (TS), and personality disorders, while the severity of clinical psychiatric picture seemed to play a secondary role. CONCLUSION: Results have shown that personality disorders and sociodemographic factors, including economic factors, seem to be major determinants of violence among patients diagnosed with mental disorders.

Health-related quality of life in outpatients with schizophrenia: factors that determine changes over time.

PURPOSE: The objective of this study was to analyze the clinical factors associated with changes in HRQoL in outpatients with schizophrenia using both generic and condition-specific HRQoL scales. METHODS: Adult outpatients with schizophrenia at least 18 years of age who did not have an acute psychotic exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions were calculated based on Lindenmayer et al.'s five factors. HRQoL data were assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires. RESULTS: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated at 12 months. Regression models showed that the factor most consistently associated with HRQoL at endpoint was change in the PANSS negative symptoms score. A decrease in the PANSS negative symptoms score from baseline to 1 year was associated with a decrease in HRQoL during the same period. There were also significant associations of the change in PANSS excitatory factor with all the HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease in all HRQoL ratings. There was also a relationship between years since onset and HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL. CONCLUSIONS: This study has found that, in outpatients with schizophrenia, changes in negative and excitement symptoms may have a greater an association with HRQoL than changes in positive, cognitive and depressive symptoms.

Paliperidone Long-Acting Plasma Level Monitoring and a New Method of Evaluation of Clinical Stability.

The second generation long-acting antipsychotics can be a pharmacologic strategy, both in the early phase of illness and in the case of low compliance. The aim of the study was to evaluate the clinical efficacy and tolerability of one monthly injection of paliperidone palmitate (PP1M), paliperidone plasma levels (PLs), and the clinical outcome. 21 outpatients, affected by Schizophrenia or Schizoaffective Disorder, were recruited. PP1M started with 150 mg on day 1 and 100 mg on day 8. Following patients were given a dosage ranging from 50 mg to 150 mg every 28 days. At baseline, and then monthly, patients were clinically evaluated. BPRS and PANSS total score showed a statistically significant decrease from T2 (after 2 months) to T12 (after 12 months). The PLs steady-state was approximatively reached after the fifth injection (T4). All the patients showed a clinical stabilization: BPRS and PANSS scores showed a significant improvement from T2. PLs data seems to suggest the initial possibility of an oral supplementation, although clinical evaluation demonstrated no relapse during the study.

The combination of pharmacogenetic and pharmacokinetic analyses to optimize clomipramine dosing in major depression: a case report.

WHAT IS KNOWN AND OBJECTIVE: Polymorphisms in cytochrome P450 2D6 and 2C19 can lead to interindividual differences in drug plasma concentrations, affecting clomipramine efficacy. Pharmacokinetic and pharmacogenetic analyses may improve drug therapy. CASE SUMMARY: We report the case of a depressed woman requiring higher doses than standard of clomipramine. Identification of low plasma drug levels led to extensive pharmacogenetic analyses of all genes and major functional polymorphisms reported to affect clomipramine metabolism. WHAT IS NEW AND CONCLUSION: Therapeutic drug monitoring and pharmacogenetic analyses may be useful in the investigation and optimization of clomipramine in standard-dose non-responders.

The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD.

In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.

"Long-acting" olanzapine in maintenance therapy of schizophrenia: A study with plasma levels.

INTRODUCTION: This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. MATERIAL AND METHODS: Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. RESULTS: BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. CONCLUSIONS: Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis.

Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15-20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia.

Autistic symptoms in unaffected first-degree relatives of people with schizophrenia: results from the Italian Network for Research on Psychoses multicenter study.

BACKGROUND: Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed. METHODS: A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures. RESULTS: Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory (p = 0.014) and Social Cognition (p = 0.025) domains and in the Global Cognition composite score (p = 0.008), as well as worse on functional capacity (p = 0.001), global psychosocial functioning (p < 0.001), real-world interpersonal relationships (p < 0.001), participation in community activities (p = 0.017), and work skills (p = 0.006). CONCLUSIONS: A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives.

Does social cognition change? Evidence after 4 years from the Italian Network for Research on Psychoses.

BACKGROUND: Deficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. METHODS: The reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. RESULTS: In 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. CONCLUSIONS: The RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery.

Sex and gender differences in clinical and functional indices in subjects with schizophrenia and healthy controls: Data from the baseline and 4-year follow-up studies of the Italian Network for Research on Psychoses.

Gender differences in clinical and psychosocial aspects of schizophrenia have been widely reported. Findings have not always been consistent, and some of them need further research. In a large sample of community dwelling persons with schizophrenia, we investigated gender differences in clinical, cognitive and functional indices, as well as their changes over a 4-year follow-up and their impact on real-life functioning. Gender differences in personal resources, cognitive and functional indices were explored also in a sample of healthy controls. Men with respect to women had an earlier age of illness onset, a worse premorbid adjustment in the academic domain, more severe avolition, expressive deficit and positive symptoms, lower prevalence of comorbidity for affective disorders, less frequent use of two coping strategies ('religion' and 'use of emotional support') and more frequent positive history of substance and alcohol abuse. In addition, men were more impaired in verbal learning, while women in reasoning/problem solving. Some patterns of gender differences observed in healthy controls were not confirmed in patients. Men's disadvantages in the clinical picture did not translate into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome.

Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial.

AIM: Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up-titration with paroxetine and a standard one. METHODS: In an open randomized, multicenter, primary-care study, 60 patients (44 women and 16 men) with PD with or without agoraphobia were enrolled and randomized to receive a slow up-titration with paroxetine (increments of 2.5 mg/day every 2 days) or a standard one (increments of 10 mg/day every week) up to a maximum daily dose of 20 mg. Repeated-measures anova on sub-items scores of the Panic Attack Anticipatory Anxiety Scale (PAAS) and Dosage Record and Treatment Emergent Symptom Scale (DOTES), respectively, used as outcome measures of effectiveness and tolerability, were performed. Significance level was set at 0.05 and it was not corrected. RESULTS: anova showed no differences between the two treatments in terms of effectiveness and tolerability. Post hoc analysis found only one significant difference in the intensity of spontaneous panic attacks (Panic and Anticipatory Anxiety Scale) in the first 9 days of treatment between the two treatment groups, which was that this item was less intense in the slow-titration group (treatment effect: F = 4.89, P = 0.03, effect size = 0.1). CONCLUSION: Present findings suggest only a small superiority for a slow up-titration regimen of paroxetine compared to a standard one in the first 9 days of treatment but no differences at end-point.

Can the Positive and Negative Syndrome scale (PANSS) differentiate treatment-resistant from non-treatment-resistant schizophrenia? A factor analytic investigation based on data from the Pattern cohort study.

Treatment-Resistant Schizophrenia (TRS) and Non-Treatment-Resistant Schizophrenia (NTRS) may represent different subtypes of schizophrenia. However, few studies have investigated their PANSS symptom dimensions by Exploratory (EFA) or Confirmatory (CFA). Data from the present study are derived from 1429 patients of the Pattern study. TRS was defined by the use of clozapine in the previous year whereas NTRS by the use of non-clozapine antipsychotics ("by proxy"). Factors were chosen based on the Kaiser criterion and considered valid when loadings were greater than or equal to 0.5. The fit to the data was evaluated by CFA in comparison with well-established PANSS models, using fit indexes. The EFA yielded similar five-factor model in both groups: Negative, Positive, Anxiety/Depression, Cognitive and Excited. CFA showed a satisfactory, but not perfect, fit to the data, as compared with the previous PANSS factor analytic models. Despite the limitations regarding the 'by proxy' definition of TRS, the results of the present study show that there are no differences in the factorial structure of PANSS in patients with TRS and NTRS.

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS).

BACKGROUND: DSM-IV identifies three stress response disorders (acute stress (ASD), post-traumatic stress (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. METHODS: This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Study participants, enrolled at 6 Italian Departments of Psychiatry, included consecutive patients with PTSD (N = 48), CG (N = 44), and controls (N = 48). RESULTS: We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. CONCLUSION: These results support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations.

Understanding the course of persistent symptoms in schizophrenia: Longitudinal findings from the pattern study.

The Pattern study was conducted to provide longitudinal observational data for individual patients with persistent symptoms of schizophrenia. Pattern is an international, multicenter, non-interventional, prospective cohort study of schizophrenia outpatients who were not considered to be in recovery. In the longitudinal phase reported herein, patients were assessed over 1 year using different clinical rating scales. Patient management followed routine local clinical practice. Primary outcome was disease state, defined by the Positive and Negative Syndrome Scale (PANSS), Negative Symptom Factor Score (NSFS), Positive Symptom Factor Score (PSFS), and Personal and Social Performance (PSP) Scale. In total, 1344 protocol-compliant patients (70.9% male) were included. Patients showed a high stability in disease state between consecutive study visits. Persistent negative persistent symptoms and symptomatic remission were the most prevalent and stable disease states. Patients in relapse generally transitioned to negative persistent symptoms or to symptomatic remission. PANSS, PSP, and quality of life ratings remained relatively stable. Relapses occurred in 10% of patients; probability of relapse was associated with younger age, extra-pyramidal symptoms, and more antipsychotic medications. Despite treatment, schizophrenia symptoms tend to remain stable over time, without overall improvement. One of the greatest challenges in schizophrenia is attainment of full symptom remission.

Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In Neurologically Asymtomatic Patients.

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged <65) showed pathological findings: 9 white matter (WM) abnormalities related to chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement.

The first model of keeping energy balance and optimal psycho affective development: Breastfed infants.

BACKGROUND: Breastfed infants follow a peculiar growth fashion characterized by a rapid weight gain in the first weeks of life, then followed by a fast decrease in growth rates, a capacity to self-regulate the sense of hungry and satiety, and a minor propensity towards overweight and obesity later on, in parallel with a better neurodevelopmental performance. METHODS: We searched studies investigating the relationship between the feeding mode in infancy and the energy balance, so the possible associations with total energy expenditure and intake regulation. We focused the research on the interaction with the neuropsychological development and the possible role of microbiome in determinating the normal generation and regular functioning of the brain through the so named "gut-brain axis". RESULTS: Total energy expenditure (TEE) is different for breast-fed and formula-fed infants, in particular the feeding mode seems to affect the sleep organisation. Long-term breastfeeding, is one of the most studied factors of neurodevelopment, several studies reporting beneficial effects on child neuropsychological development. Probably this effect is modulated by genetic variations in fatty acid metabolism. Increasing data also showed that the intestinal microbiome exerts several functions which are able to influence neurodevelopment. LIMITATIONS: There is considerable controversy over whether nutrition in early life has a long-term influence on neurodevelopment. Other studies are needed to confirm the association between breastfeeding and brain development. CONCLUSIONS: The key points of energy disposal, the role and effects of the instestinal flora represent promising fields of investigation possibly leading to indications for the wide area of preventive medicine.

Similar white matter changes in schizophrenia and bipolar disorder: A tract-based spatial statistics study.

Several strands of evidence reported a significant overlapping, in terms of clinical symptoms, epidemiology and treatment response, between the two major psychotic disorders-Schizophrenia (SCZ) and Bipolar Disorder (BD). Nevertheless, the shared neurobiological correlates of these two disorders are far from conclusive. This study aims toward a better understanding of possible common microstructural brain alterations in SCZ and BD. Magnetic Resonance Diffusion data of 33 patients with BD, 19 with SCZ and 35 healthy controls were acquired. Diffusion indexes were calculated, then analyzed using Tract-Based Spatial Statistics (TBSS). We tested correlations with clinical and psychological variables. In both patient groups mean diffusion (MD), volume ratio (VR) and radial diffusivity (RD) showed a significant increase, while fractional anisotropy (FA) and mode (MO) decreased compared to the healthy group. Changes in diffusion were located, for both diseases, in the fronto-temporal and callosal networks. Finally, no significant differences were identified between patient groups, and a significant correlations between length of disease and FA and VR within the corpus callosum, corona radiata and thalamic radiation were observed in bipolar disorder. To our knowledge, this is the first study applying TBSS on all the DTI indexes at the same time in both patient groups showing that they share similar impairments in microstructural connectivity, with particular regards to fronto-temporal and callosal communication, which are likely to worsen over time. Such features may represent neural common underpinnings characterizing major psychoses and confirm the central role of white matter pathology in schizophrenia and bipolar disorder.

DTI and Myelin Plasticity in Bipolar Disorder: Integrating Neuroimaging and Neuropathological Findings.

Bipolar disorder (BD) is a major psychiatric illness with a chronic recurrent course, ranked among the worldwide leading disabling diseases. Its pathophysiology is still not completely understood and findings are still inconclusive, though a great interest on the topic has been constantly raised by magnetic resonance imaging, genetic and neuropathological studies. In recent years, diffusion tensor imaging (DTI) investigations have prompted interest in the key role of white matter (WM) abnormalities in BD. In this report, we summarize and comment recent findings from DTI studies in BD, reporting fractional anisotropy as putative measure of WM integrity, as well as recent data from neuropathological studies focusing on oligodendrocyte involvement in WM alterations in BD. DTI research indicates that BD is most commonly associated with a WM disruption within the fronto-limbic network, which may be accompanied by other WM changes spread throughout temporal and parietal regions. Neuropathological studies, mainly focused on the fronto-limbic network, have repeatedly shown a loss in cortical and subcortical oligodendrocyte cell count, although an increased subcortical oligodendrocyte density has been also documented suggesting a putative role in remyelination processes for oligodendrocytes in BD. According to our review, a greater integration between DTI and morphological findings is needed in order to elucidate processes affecting WM, either glial loss or myelin plasticity, on the basis of a more targeted research in BD.

Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics.

OBJECTIVES: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). METHODS: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS: The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition. CONCLUSIONS: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

The epidemiology of generalized anxiety disorder in Europe.

The objective of this paper is to provide a review on available data to date on the epidemiology of GAD in Europe, and to highlight areas for future research. MEDLINE searches were performed and supplemented by consultations with experts across Europe to identify non-published reports. Despite variations in the design of studies, available data suggest that (a) about 2% of the adult population in the community is affected (12-month prevalence), (b) GAD is one of the most frequent (up to 10%) of all mental disorders seen in primary care, (c) GAD is a highly impairing condition often comorbid with other mental disorders, (d) GAD patients are high utilizers of healthcare resources, and (e) despite the high prevalence of GAD in primary care, its recognition in general practice is relatively low. Marked data deficits are: lack of data from eastern European countries, lack of information about the natural course of GAD in unselected samples, the vulnerability and risk factors involved in the aetiology of GAD and lack of data about adequate and inappropriate treatments in GAD patients as well as the associated and societal costs of GAD.