Personalized medicine begins with the phenotype: identifying antipsychotic response phenotypes in a first-episode psychosis cohort.

AIMS: Here, we present a clustering strategy to identify phenotypes of antipsychotic (AP) response by using longitudinal data from patients presenting first-episode psychosis (FEP). METHOD: One hundred and ninety FEP with complete data were selected from the PEPs project. The efficacy was assessed using total PANSS, and adverse effects using total UKU, during one-year follow-up. We used the Klm3D method to cluster longitudinal data. RESULTS: We identified four clusters: cluster A, drug not toxic and beneficial; cluster B, drug beneficial but toxic; cluster C, drug neither toxic nor beneficial; and cluster D, drug toxic and not beneficial. These groups significantly differ in baseline demographics, clinical, and neuropsychological characteristics (PAS, total PANSS, DUP, insight, pIQ, age of onset, cocaine use and family history of mental illness). CONCLUSIONS: The results presented here allow the identification of phenotypes of AP response that differ in well-known simple and classic clinical variables opening the door to clinical prediction and application of personalized medicine.

Patient characteristics driving clinical utility in psychiatric pharmacogenetics: a reanalysis from the AB-GEN multicentric trial.

Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode.Trial registration ClinicalTrials.gov NCT02529462.

Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes.

This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 × 10(-4)). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS.

Occupational disability in bipolar disorder: analysis of predictors of being on severe disablement benefit (PREBIS study data).

OBJECTIVE: Patients diagnosed with bipolar disorder (BD) are reported to have significant work impairment during interepisode intervals. This study was carried out to assess potential predictors of occupational disability in a longitudinal follow-up of euthymic patients. METHOD: We included 327 euthymic patients diagnosed with BD type I or type II, 226 of whom were employed and 101 were receiving a severe disablement benefit (SDB). Sociodemographic data were studied and episode recurrence was assessed along a 1-year follow-up. Logistic regression analysis was applied to determine predictors of receiving SDB. Cox regression was built to study recurrences. RESULTS: Predictors of receiving SDB were: axis II comorbidity [Odds Ratio (OR) = 2.94, CI: 1.26-6.86, P = 0.013], number of manic episodes (OR = 1.21, CI: 1.10-1.34, P < 0.001), being without stable partner (OR = 2.44, CI: 1.34-4.44, P = 0.004) and older age (OR = 1.08, CI: 1.05-1.12, P < 0.001). Bipolar patients receiving SDB presented more episodic recurrences regardless of polarity than employed bipolar patients (P = 0.002). The time until recurrence in 25% of the bipolar patients receiving SDB was 6.08 months (CI: 4.44-11.77) being 13.08 months (CI: 9.60 to -) in the employed group. CONCLUSION: Occupational disability in bipolar patients is associated with axis II comorbidity, more previous manic episodes, not having a stable relationship, older age, and more recurrences at 1-year follow-up.

Change in psychiatrists' attitudes towards the physical health care of patients with schizophrenia coinciding with the dissemination of the consensus on physical health in patients with schizophrenia.

PURPOSE: To evaluate the impact of the "Spanish Consensus on Physical Health in Patients with Schizophrenia" on psychiatrists' evaluations of the physical health of patients with schizophrenia. METHOD: Epidemiological, non-interventional, national, multicentre study, with two retrospective, cross-sectional data collection stages in which 229 psychiatrists evaluated 1193 clinical records of patients with schizophrenia (ICD-10) seen in January and September of 2007. RESULTS: Mean age of the patients was 39.7±11.6 years, 65.5% were men, diagnosed for schizophrenia 14.0±10.3 years ago. Forty percent of the patients suffer from a concomitant disease, the most prevalent being hypercholesterolemia (46.3%), hypertriglyceridaemia (33.5%) and arterial hypertension (26.0%). The difference in the number of patients who had all the physical measurements taken between the two cross-sectional evaluations was 13.8% (CI: 11.8%, 15.7%). The differences for each parameter were: weight 13.7% (CI: 11.7%, 15.6%), BMI 13.58% (CI: 11.6%, 15.5%), waist circumference 14.0% (CI: 12.0%, 15.39%), lipid profile 2.9% (CI: 1.9%, 3.9%) and glycaemia 2.6% (CI: 1.7%, 3.5%). CONCLUSIONS: These results imply that the dissemination of the "Consensus on Physical Health in Schizophrenia Patients", and possibly other actions, has made psychiatrists more aware of an integral approach to patients with schizophrenia, promoting increased monitoring of the physical health of these patients.

P300 event-related potential in euthymic patients with bipolar disorder.

Auditory P300 event-related potential (ERP) and performance on Sustained Attention were evaluated in 24 euthymic bipolar patients and 38 healthy volunteers. There were no significant differences between groups, and performance in sustained attention had no significant influence in the P300 responses. P300 response might be driven by the presence of mood symptoms.

Severity of personality disorders and suicide attempt.

OBJECTIVE: Severity of personality disorders (PDs) may be more useful in estimating suicide risk than the diagnosis of specific PDs. We hypothesized that suicide attempters with severe PD would present more attempts and attempts of greater severity/lethality. METHOD: Four hundred and forty-six suicide attempters were assessed. PD diagnosis was made using the International Personality Disorder Questionnaire--Screening Questionnaire. PDs were classified using Tyrer and Johnson's classification of severity (no PD, simple PD, diffuse PD). Severity/lethality of attempts was measured with the Suicide Intent Scale, Risk-Rescue Rating Scale and Lethality Rating Scale. RESULTS: Attempters with severe (diffuse) PD had more attempts than the other groups. After controlling for age and gender, this difference remained significant only for the younger age group and women. There was no relationship between severity of PDs and severity/lethality of attempts. CONCLUSION: Younger female attempters with severe PD are prone to repeated attempts. However, the severity of PD was not related to the severity/lethality of suicide attempts.

[Consensus on physical health of patients with schizophrenia from the Spanish Societies of Psychiatry and Biological Psychiatry]. / Consenso sobre la salud física del paciente conesquizofrenia de las Sociedades Españolasde Psiquiatría y de Psiquiatría Biológica.

INTRODUCTION: Schizophrenia has traditionally been associated with higher rates of physical comorbidity and excess mortality. OBJECTIVE: To develop a Spanish consensus document concerning the physical health of patients with schizophrenia and the interventions required to reduce the over-morbidity and over-mortality of these patients. Method. The process consisted of: a) systematic review of the literature in the Medline database up to January 2006 and manual review of the bibliographical references of the papers obtained; b) reviews of national and international guides by the coordinating committee and medical specialist acting as expert advisors; c) multidisciplinary consensus meetings, and d) editing of the final consensus document. RESULTS: Compared to the general population, patients with schizophrenia present higher rates of infection (HBV, HCV, HIV), endocrine/metabolic disorders, cardiac and respiratory diseases (over-morbidity) and higher global death risk, as well as death from natural causes--basically respiratory, cardiovascular and oncological diseases (over-mortality). As a guide, therefore, this document proposes a series of interventions to be performed by psychiatrists to reduce the current rates. CONCLUSIONS: Given the over-morbidity and overmortality of patients with schizophrenia, awareness of these aspects should be increased among primary healthcare providers and specialists, including psychiatrists, and physical health problems should be incorporated into psycho-educational programs, and treatment compliance and severe mental disorder treatment units.

A bibliometric study of the use of the classification and diagnostic systems in psychiatry over the last 25 years.

BACKGROUND: Our purpose was to examine the use of classification and diagnostic systems in the field of psychiatry (CDSP) from a bibliometric perspective, over the period 1980-2005. METHODS: We selected (in EMBASE and MEDLINE databases) documents that contained, in any of their sections, the descriptors 'psychiatr*', 'DSM*', 'ICD*', or 'diagnostic criteria',as well as other more specific descriptors. As a bibliometric indicator of production we applied Price's law. We also calculated the national participation index (PI) and correlated it with overall PI in biomedical and health sciences, and with PI in the discipline of psychiatry. RESULTS: We obtained 20,564 original documents; 15,743 referred to the Diagnostic and Statistical Manual of Mental Disorders (DSM) and 3,106 to the International Classification of Diseases (ICD). Our results indicate non-fulfilment of Price's law, since scientific production on CDSP does not undergo exponential growth (correlation coefficient r = 0.9651, vs. r = 0.9927 after linear adjustment). Of the 10 journals with the highest impact factor in the field of psychiatry, the Journal of Clinical Psychiatry has the highest PI in the DSM subgroup (PI = 14.77), and the British Journal of Psychiatry in the ICD subgroup (PI = 1.54). The principal producer country is the United States (PI = 37.9), though in proportion to its production in the psychiatric field the ranking is headed by Finland. Only 10 countries, of the 20 major producers in health sciences, surpass their own PI in the field of psychiatry (Brazil, Italy, Japan, Austria, Spain, Germany, France, India, Switzerland, and China). CONCLUSIONS: Over recent years, the use of CDSP (basically the DSM or ICD) in the scientific literature has increased. Nevertheless, the abstracts to these studies, included in the principal databases, should always specify the diagnostic criteria employed, with a view to increasing information levels and reliability for the reader.

Diagnostic stability and evolution of bipolar disorder in clinical practice: a prospective cohort study.

OBJECTIVE: To evaluate the long-term stability of International Classification of Diseases-10th revision bipolar affective disorder (BD) in multiple settings. METHOD: A total of 34 368 patients received psychiatric care in the catchment area of a Spanish hospital (1992-2004). The analyzed sample included patients aged > or =18 years who were assessed on > or =10 occasions and received a diagnosis of BD at least once (n = 1153; 71,543 assessments). Prospective and retrospective consistencies and the proportion of subjects who received a BD diagnosis in > or =75% of assessments were calculated. Factors related to diagnostic shift were analyzed with traditional statistical methods and Markov's models. RESULTS: Thirty per cent of patients received a BD diagnosis in the first assessment and 38% in the last assessment. Prospective and retrospective consistencies were 49% and 38%. Twenty-three per cent of patients received a BD diagnosis during > or =75% of the assessments. CONCLUSION: There was a high prevalence of misdiagnosis and diagnostic shift from other psychiatric disorders to BD. Temporal consistency was lower than in other studies.

No association between the Ser9Gly polymorphism of the dopamine D3 receptor gene and schizophrenia in a Spanish sample.

This study aims to further evaluate the controversial association between the Ser9Gly polymorphism in codon 9 of the D3 dopamine receptor gene (DRD3) and schizophrenia in psychiatric inpatients acutely hospitalized in two general hospitals in Madrid, Spain. The Ser9Gly polymorphism of the DRD3 was examined in 178 schizophrenic patients, 286 patients with other psychiatric diagnoses, and 132 controls recruited. Genotype frequencies were in Hardy-Weinberg equilibrium. No association was found between schizophrenia and the Ser9Gly polymorphism of the D3 dopamine receptor gene.

[Acute tryptophan depletion in eating disorders]. / Depleción aguda de triptófano en trastornos de la conducta alimentaria.

INTRODUCTION: This work describes the rational bases justifying the use of acute tryptophan depletion technique in eating disorders (ED) and the methods and design used in our studies. Tryptophan depletion technique has been described and used in previous studies safely and makes it possible to evaluate the brain serotonin activity. Therefore it is used in the investigation of hypotheses on serotonergic deficiency in eating disorders. Furthermore, and given the relationship of the dysfunctions of serotonin activity with impulsive symptoms, the technique may be useful in biological differentiation of different subtypes, that is restrictive and bulimic, of ED. METHODS: 57 female patients with DSM-IV eating disorders and 20 female controls were investigated with the tryptophan depletion test. A tryptophan-free amino acid solution was administered orally after a two-day low tryptophan diet to patients and controls. Free plasma tryptophan was measured at two and five hours following administration of the drink. Eating and emotional responses were measured with specific scales for five hours following the depletion. A study of the basic characteristics of the personality and impulsivity traits was also done. Relationship of the response to the test with the different clinical subtypes and with the temperamental and impulsive characteristics of the patients was studied. RESULTS: The test was effective in considerably reducing plasma tryptophan in five hours from baseline levels (76%) in the global sample. The test was well tolerated and no severe adverse effects were reported. Two patients withdrew from the test due to gastric intolerance. CONCLUSIONS: The tryptophan depletion test could be of value to study involvement of serotonin deficits in the symptomatology and pathophysiology of eating disorders.

[Complications of dysmorphophobia. Description of a self-mutilation case]. / Complicaciones de la dismorfofobia. Descripción de un caso de automutilación.

Dysmorphophobia, also known as Body Dysmorphic Disorder (BDD), can become a serious illness that results in severe complications such as social isolation, self-mutilations, suicide attempts, and even suicide. Many authors currently include BDD among the spectrum of obsessive-compulsive disorders. There are two distinguishable variants of BDD: psychotic and non-psychotic. The current trend considers these variants as one same disorder characterized by an insight spectrum. However, the psychotic variant exhibits more severe symptoms. We present a case of dysmorphophobia with psychotic symptoms that required psychiatric hospitalization due to serious complications. We discuss the presence of tactile and propioceptive sensations in some BDD patients and their contribution to their distress. Finally, we discuss a great propensity of BDD patients to conceal their symptoms. Thus, it is important for the clinician to specifically inquire about these symptoms, especially in high-risk groups, to prevent occurrence of serious complications.

Ziprasidone: from pharmacology to the clinical practice. One year of experience.

More than a year after the marketing of the atypical anti-psychotic ziprasidone, data from research studies and clinical practice have provided a fair amount of useful information for its practical use in the treatment of schizophrenia. Its pharmacodynamical characteristics and the results from clinical trials with a flexible dose seem to justify the need to administer doses in a range higher than what was initially foreseen, with an initial minimum of 120 mg per day and a fast titulation up to 160 mg per day. Such doses make it possible to achieve sufficient plasma concentrations to occupy at least 60 % of the D2 receptors from which the anti-psychotic effect derives. Moreover, its anti-depressive activity and its non-sedative profile have been confirmed, with a favorable effect on attention and other cognitive functions of the patient, according to its high affinity for 5HT1A and D1 receptors and the inhibition of serotonin and noradrenaline re-uptake. Finally, the low affinity of this drug for alpha-adrenergic, histaminergic and muscarinic receptors favors a good tolerability profile, with a neutral effect on weight, and a lack of anti-cholinergic effects. Results from different clinical trials show that the use of doses in the higher range is associated to a faster and more pronounced clinical improvement without adding a higher risk of adverse events.

Process of adaptation to Spanish of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Scale. Self applied version (TEMPS-A).

INTRODUCTION: Investigation of the predisposing factors for affective disorders has shown that measures to assess affective temperament are necessary. The TEMPS-A is a self-evaluation measure to assess four affective temperaments (hyperthymic, depressive, cyclothymic and irritable) and anxious temperament. METHOD: The TEMPS-A questionnaire version that includes 110 questions has been adapted following the translation-backtranslation methodology, including two translations to Spanish and the classification of equivalence to English by an independent author. RESULTS: The study results indicated that a satisfactory translation was obtained, as indicated by the validation of equivalence by the bilingual consultant. All the items showed a perfect (A) or satisfactory equivalence (B). CONCLUSIONS: The TEMPS-A, Spanish version, is an understandable questionnaire that is equivalent to the original version in English, that allows for the evaluation of affective temperaments.

[Pharmacological treatment of depression]. / Tratamiento farmacológico de la depresión.

Depression is a disorder with higher prevalence that generates important costs in the personal and socioeconomic fields. We have currently various antidepressants drugs for its treatment. In this article a review of these drugs is carried out, including various approaches necessary for addressing the special characteristics of each clinical situation. Pharmacological strategies for resistant depression are evaluated later. Finally, the future research lines are analyzed in order to improve the pharmacological depression treatment.

[Cycloid psychoses. A case report]. / Psicosis cicloide. A propósito de un caso.

Cycloid psychoses, described by Leonhard, have a sudden onset, unstable polymorphic delusion symptomatology, labile state of consciousness, lack of physical symptoms, quick remission with no residual mental abnormalities and normality between episodes. Leonhard distinguished three clinical forms: anxiety-happiness psychosis, excited-inhibited confusion psychosis and hyperkinetic-akinetic motility psychosis. The essential characteristics of this clinical subtypes are: polymorphism, global disturbance of psychic life, acute appearance of symptoms, total insomnia 3 days before onset of symptomatology, intra and interepisode lability, polar structure, tendency to repetition of episodes (phases) and a good long-term prognosis. We present a patient's clinical history and evolution that illustrate the characteristics of this kind of endogenous psychoses.

New GABAA receptor alpha5 subunit gene polymorphism that may confound genotyping.

We report the discovery of a new GABAA receptor alpha5 subunit gene polymorphism close to the polymorphism described by Glatt et al. (GT)5GCGTGC(GT)21. This new polymorphism is of great importance, because it means that non-denaturing acrylamide gels used to separate the different alleles of the polymorphism described by Glatt et al. cannot distinguish an allele with the sequence: (GT)4GCGTGC(GT)n from another allele with the sequence: (GT)4(GCGT)4GC(GT)(n-6). These gel fragments are separated by size, which would be the same in these two cases. An alternative would be to use an analysis method that can detect base changes, for instance, single strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE).