Control of gene expression is essential for the establishment and maintenance of all cell types, and is involved in pathogenesis of several diseases. Accurate computational predictions of transcription factor regulation may thus help in understanding complex diseases, including mental disorders in which dysregulation of neural gene expression is thought to play a key role. However, predictions via bioinformatics tools are typically poorly specific.

We have developed and tested a computational workflow to computationally predict Transcription Factor Binding Sites on proximal promoters of vertebrate genes. The computational framework was applied to groups of genes found to respond to antipsychotic drugs. Our approach for the prediction of regulatory elements is based on a search for known regulatory motifs retrieved from TRANSFAC, on DNA sequences of genes' promoters. Predictions are thus weighted by conservation. These predictions are further refined using a logistic regression to integrate data from co-regulated genes.

Consistent results were obtained on a large simulated dataset consisting of 5460 simulated promoter sequences, and on a set of 377 vertebrate gene promoters for which binding sites are known (TRANSFAC gene set).

Our results show that integrating information from multiple data sources, such as genomic sequence of genes' promoters, conservation over multiple species, and gene expression data, can improve the accuracy of computational predictions. The results of predictions on genes involved in antipsychotics response include the drug target Homer 1, involved in glutamate synaptic plasticity response.

Training programs for people that are occupied with mental health are a vital part of their lifelong education, along with the general evolution of psychiatric services.

The aim of this study was to validate a questionnaire, previously constructed by one of the authors, measuring satisfaction from training programs relevant to mental health.

65 trainees that had participated in three different training programs completed a satisfaction questionnaire, comprising of 4 general subscales (educational materials, trainers, organization, general satisfaction) and 2 specific subscales (satisfaction from training program content, attitude towards trainees' efficacy). 19 of them completed it twice, in two weeks' time.

The general part of the questionnaire preserved approximately its original factor structure. Reliability of the subscales was high (Cronbach's alpha was 0.84-0.86 for the three first, 0.77 for the last subscale, 0.94 for the total). Test-retest reliability was very high (Pearson's r was 0.90-0.94 for the subscales 0.98 for the total). Comments on each training program, evaluated by two independent raters (Cohen's kappa=0.96) correlated significantly with the total satisfaction score.

The 4 general subscales of this satisfaction questionnaire have demonstrated sufficient psychometric characteristics: factorial and external criterion validity, test-retest reliability and internal consistency, and are therefore proposed to be used, along with content-specific subscales, for the evaluation of any training program in psychiatry.

The CLP is the operative area where psychosomatic theories and clinical practice meet, and the moment when psychiatry meets the rest of medicine, aiming at building an efficient communication. CLP activities are founded on a good relationship with colleagues, being the referring physician the actual “first client” of a CLP intervention, even before of the patient.

We administrated an anonymous and self-compiled questionnaire to 330 doctors and head-nurses of different wards of the Modena General Hospital, questioning about their opinions on usefulness, efficiency, relevance to everyday clinical practice of the CLP Service.

109 of the 330 questionnaires were answered back (33%); 63.3% of the sample judged “very useful” our Service. 89.9% expressed positive opinion about the presence of a single, “dedicated” consultant for their ward. Most useful aspects of our intervention are considered to be: advices on psychothropic drug therapy (84.4%); talking with the patient (73.4%); interventions on the families (73.4%) and organizing care after discharge (33.9%).

Data from our study support the concept of how useful is the role of psychiatric operators in the contest of GH, and that GH ward staff seem to share this opinion. Very few studies exist on feedback to CLP activities, in spite of the relevance of the subject: being aware of needs, expectations and opinions of our colleagues is (one of) the starting points defining CLP identity and mission.

Most studies of patients subject to compulsory admission to psychiatric hospital examine only the population of those already subject to compulsion. This prospective study examines the whole population of patients who have been formally assessed for compulsory admission, and includes those where the decision was taken not to proceed with compulsory admission.

All Approved Social Workers in the County of Norfolk were asked to complete data collection sheets contemporaneously for each formal assessment for admission taking place in terms of the Mental Health Act 1983 over the period 2001 – 2006 inclusive. This data was then collated centrally and subject to analysis regarding demographic and other factors associated with requests for assessment and decisions to actually use compulsory admission powers.

Data on about 5000 individual formal Mental Health Act 1983 assessments were collected representing over 95% of the total number of such assessments carried out during this period in Norfolk.

There were significant associations between gender, age, marital status and accommodation and both referral for formal assessment and compulsory admission to psychiatric hospital. Some aspects of these associations were unexpected and are discussed further.

Agitation is a common symptom in schizophrenia and bipolar mania, causing marked distress and posing considerable risks for patients. Intramuscular formulations of psychotropic medication can provide a fast acting treatment of severe agitation in patients with acute episodes of schizophrenia or mania. As effective as these treatments are, particular antipsychotics can be associated with a heightened risk of dystonia and related Extrapyramidal Symptoms (EPS). Patients presenting to emergency care settings are also likely to have coexisting intoxications and medical conditions that may contribute to this risk.

The aim of this observational prospective study was to document the safety and effectiveness of all IM psychotropic drugs during the 24 hours following an initial injection in acutely agitated patients suffering from schizophrenia or bipolar disorder under naturalistic conditions.

Two-hundred-thirty-two (232) participating investigator sites (12 European countries) observed 1940 patients (mean age: 39 y, 42% female, 66% schizophrenia diagnosis). The primary endpoint was the occurrence of extrapyramidal symptoms (EPS), further endpoints were clinical severity measured by PANSS-EC and CGI-S. A total of 1311 (68%) patients received a monotherapy injection at baseline. Within 24 hours after the first injection, 190 (10%) of all 1940 patients experienced EPS. All intramuscular psychotropic drugs were shown to be effective in reducing measures of acute agitation.

This study provides favourable results on EPS related adverse events and effectiveness of intramuscular psychotropic medication for the management of acute agitation in patients within a naturalistic setting during the first 24 hours of treatment.

The risk of abuse/dependence of alcohol or drugs in schizofrenia have been estimed about 4 times the prevalence in general population. This fact difficults the treatment results and efficcacy: more relapses, more treatments withdrawal and poorer prognosis. The aims of our study is to evaluate the effect of Zyprasidone, an atypical antipsychotic with 5HT propierties, in patients with schizofrenia and comorbid substance use disorder in a single, open, prospective-naturalistic design.

36 outpatients were selected with Schizofrenic disorder diagnosis (DSMIV) and abuse/dependence of at least 1 substance in which Zyprasidone was recommended (inneficacy, intolerance of prior treatments,..). They were evaluated clinically and data about actual consum and craving were collected at inicial visit and follow-up monthly (3 to 6 months). Results were analized with SPSS pack.

The mean follow-up period was 3 month. 28 patients finished the evaluation showing a decrease in clinical measures (PANSS, ICG) with good tolerance (only 4 drop-outs associated to indesirable effects). The most frequent drug use disorder was tobacco followed by alcohol and cannabis.The results on number and frequency of drug use shows a slow tendency to reduce at the end of the evaluation as well the craving measures but no significant differences were found.

Our exploratory study with Zyprasidone, althougt metodological limitations, suggests that clinical schizofrenic symptoms can improve but also drug pattern use. Naturalistic studies of schizofrenia with comorbid substance use disorder can be useful to show the efficacy of antipsychotics in real clinical practice

Prolactin (PRL) data from adolescents treated with olanzapine are presented.

Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.

Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.

Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.

The changes in metabolic parameters in olanzapine-treated adolescents were examined.

Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.

Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).

Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.

Some atypical antipsychotics particularly clozapine and olanzapine have serious metabolic side effects like metabolic syndrome.

To determine whether olanzapine-induced metabolic abnormalities identified through monitoring can be changed by switching to aripiprazole in patients with schizophrenia.

Current research show that fifty stable outpatients suffering from metabolic side effects due to olanzapine medication were switched to an open-label, flexible-dose of aripiprazole (10-30 mg/day) in this 13-week naturalistic study. An extensive metabolic evaluation was conducted on all patients, at baseline, at 6 weeks, and at 13 weeks post switch. Metabolic abnormalities consist of new onset diabetes, impaired fasting glucose, impaired glucose tolerance, metabolic syndrome according to various definitions, and dyslipidemia. After 13 weeks of treatment with aripiprazole (mean dosage 16.8 mg / day), there was a significant decrease in body weight, body mass index, and waist circumference. The rates of in fasting glucose, fasting insulin, insulin resistance index, and serum lipids levels (cholesterol, triglycerides, low-density lipoprotein (LDL), LDL/HDL, Chol/HDL, and non-HDL cholesterol) were reduced. Also three subjects with recent onset diabetes were reversed at 3 months follow-up. The metabolic syndrome was reversed in 64% of patients at 3 months.

The change of psychotropic drug treatment from olanzapine to aripiprazole in stable outpatients with schizophrenia was generally well tolerated and was associated with significant improvements at 13 weeks. Results support the reversibility of olanzapine-induced metabolic abnormalities when detected early and followed by a switch to aripiprazole.

CYP2D6 metabolizes risperidone into 9-hydroxi-risperidone, as well as other drugs. CYP2D6 shows genetic polymorphism, and 6-8% of Caucasians are “slow metabolizers”. “Fast metabolizers” show lower plasma levels of risperidone and higher levels of 9-hydroxi-risperidone than “slow metabolizers”. The aim of this study is to collect information about the hypothetical relationship between metabolism phenotype and parameters related to sanitary resources utilization in patients treated with risperidone.

Plasma levels of risperidone and 9-hydroxi-risperidone were determined in 52 patients treated at the Acute Unit setting, to establish their metabolism phenotype. Patients were grouped as fast (n=11), slow (n=13) or intermediate metabolizers (n=28), according to risperidone/9-hydroxi-risperidone ratio logarithm and using eighty and twenty percentiles as cut-points. Hospitalizations, emergency services utilization and visits to community mental health center during two years were recorded in the three groups.

Fast metabolizers showed a higher mean number of visits to community mental health centers (35.7 vs 24.8, fast and slow metabolizers respectively, p=0.667), a higher mean number of hospitalizations (2.45 vs 1.3, fast and slow metabolizers respectively; p=0.091), a longer mean length of hospitalizations (57.3 vs 47.6 days, fast and slow metabolizers respectively; p=0.581) and a higher number of visits to emergency services (2.45 vs 1, fast and slow metabolizers respectively; p=0.01), although differences only reached statistical significance in this last parameter.

In spite of methodological limitations (mainly the small sample size), the present study shows some preliminary evidence about the influence of pharmacogenetic factors on the evolution of psychotic patients treated with risperidone.

To determine whether depot patients on typical antipsychotics may benefit from a treatment switch.

Outpatients with a reported diagnosis of schizophrenia attending a depot clinic in Dewsbury, UK, were given full psychiatric and physical reviews. Recommendation of patients' future treatment was based on findings. Treatment switches were made three months after baseline assessments.

Of 111 patients considered for review, 108 (63 men/45 women) were assessed; 94.4% had a diagnosis of schizophrenia. Before review, 98% received typical antipsychotic depot preparations and 2% the long-acting atypical antipsychotic, Risperdal Consta. Nearly two-thirds (63.0%) received flupentixol decanoate. Following review, 74.1% patients received long-acting injectable medication, 24.1% oral medication and two patients discontinued treatment. Of those on long-acting injectable antipsychotics, 85.0% received typical depots; 15.0% Risperdal Consta. Most (92.3%) oral medications were atypical antipsychotics. Nearly two-thirds of patients (62.0%) continued on the same medication. On review, hyperprolactinaemia was found in 28 (25.9%) patients, particularly women; treatment was changed for 17 patients, mainly to Risperdal Consta. Eleven (10.2%) patients had glucose abnormalities; treatment was changed for three to risperidone preparations. 41.7% patients had other biochemical abnormalities, mainly liver function tests and dyslipidaemia. Nearly 40% were hypertensive and around one-quarter had electrocardiogram abnormalities.

Data suggest that depot patients on typical antipsychotics may benefit from medication review to consider use of atypicals and other newer classes of antipsychotics, and that health monitoring of these patients may be prudent.

To evaluate the efficacy of risperidone long-acting injectable (RLAI) for reducing negative symptoms of schizophrenia in patients with predominantly negative symptoms at baseline.

This subanalysis on data from the 6-month, open-label Switch to Risperidone Microspheres (StoRMi) trial included patients with Positive and Negative Syndrome Scale (PANSS) negative subscale score >= 21, which was higher than their PANSS positive subscale score. Improvement in negative symptoms was assessed on the PANSS negative subscale and the negative factor score based on [1]. Additional outcome variables included measures in general functioning, quality of life, and patient satisfaction.

A total of 842 patients were eligible for inclusion in this subanalysis. Six months of treatment were completed by 631 (74.9%) patients. 43 (5.1%) patients discontinued treatment due to an adverse event. Negative symptoms were significantly reduced by 6.1 +/- 6.3 points for the PANSS negative score and 6.1 +/- 6.4 points for the negative factor score1, (P<0.0001 for both). Significant improvements were also noted for total PANSS and other PANSS subscale scores, general functioning, quality of life, and patient satisfaction (P<0.0001). The most common treatment-emergent adverse events (>5%): anxiety (6.8% of patients), exacerbation of disease (6.2%), and insomnia (5.7%). Overall RLAI was well tolerated and associated with significant reductions in movement disorder severity.

RLAI treatment resulted in significant improvement in negative symptom severity and was well tolerated in patients with predominantly negative symptoms, who switched from a stable antipsychotic regimen.

Mental health-related visits to emergency departments are growing. Research on the decision making process in psychiatric emergency services (PES) has focused on the severity of symptoms and dangerousness as predictors of admission or discharge. Patient requests have been understudied in this predominantly medical approach.

The main objective of this study was a standardized evaluation of patient requests in PES.

The ‘Hulpvragenlijst’ (HVL), a 61-item self-rating questionnaire was administered to 102 consecutive patients attending the PES of a general hospital. The HVL assesses 7 different components of patient requests: psychological, relational, problem-oriented, medical, information-oriented, and psychiatric. Exclusion criteria were disturbed consciousness and severe psychomotor agitation.

Data processing following the rules of HVL aggregation was performed. Ridit analysis was further used for refined data aggregation. This is a method for comparing ordinal-scale responses. Patient requests were looked at in different subgroups (according to diagnosis and disposition).

Data processing following the rules of HVL aggregation showed that the main request of patients was information-oriented, less relational or medical. Ridit analysis showed a more refined pattern of requests in different diagnostic and dispositional categories: each category characterized by a distinct profile of requests.

Patient requests, besides the severity of symptoms and dangerousness, are a supplemental view on the needs of patients attending PES. These different components should be entered into a “negotiation” that ultimately results in a treatment decision. If confirmed in other studies these data could be used for the future development of PES service delivery.

Schizophrenics differ in their outcome mainly because different response and side effects to treatment, and clinicians do not have good instruments to choose the best antipsychotic (AP) for each individual. Weight gain is a frequently observed side effect with many AP treatments and seems to be underreported and under-recognized in many patients.

The potential effect of the Trp64Arg variant in beta3 adrenergic receptor gene on weight gain and obesity was investigated applying meta-analytic techniques, combining all published data while restricting our analysis to studies investigating the Trp64Arg in antipsychotic-induced weight gain and obesity. We also investigated whether ancestry (Caucasian versus African-American) and clinical factors moderated any association.

We found no evidence for association of the Arg64 allele with weight gain and obesity (z= 0.49 p = 0.626) but without significant between studies heterogeneity (chi-squared = 0.17 (d.f. = 1) p = 0.678).

Our meta-analysis does not provide support for the association of Trp64Arg in weight gain but indicates that firmly establishing the role of pharmacogenetics in clinical psychiatry requires much larger sample sizes that have been hitherto reported. On the other hand, the number of the studies employing psychotic patients is too small compared to the number of studies that have investigated this polymorphism in obesity.

It is well known the difficulties found in making most psychotic patients follow a long-lasting oral treatment.To overcome this problem, injected drugs were developed over the last decades. One of the main side effects of these drugs is weight gain. To asess its importance in the newest long –acting injection of risperidone, a retrospective study was developed.

Clinical records of 61 patients with injected risperidone were reviewed, obtaining data about pre-treatment weight and weight after a year of bimensual injections. Patients with eating disorders or organic pathology were excluded. Other variables were recorded: doses, other injected treatments in the previous year and the weight gain, and coadyuvant oral treatment of neuroleptics during the studied period.

No statistically significant weight differences were found during the first year of treatment (p>0.05). When considering doses, or patients with coadyuvant therapy of low-dose neuroleptics, no difference was found either (p>0.05).

23 of these patients followed another long-lasting injected treatment for at least a year before sweeping to risperidone. A bigger weight gain was was found in that previous period of time than in the following year with risperidone (p=0.037).

Compliance to treatment is one of the keys to success in schyzophrenia management. Side effects may hazard this compliance: injected long-lasting risperidone seems to minimize weight gain in these patients, compared to previous injected drugs, making it easier to follow these prolonged treatments.

Psychiatric disorders are considered to be universal, being found in all types of societies, from small nomadic groups to large complex civilizations. We can understand Cultural Psychiatry as a perspective that looks for comprehension of psychiatric disorders from the viewpoint of systems of meanings and values prevalent in a society. It went through great developments in the last 20-30 years, becoming extremely relevant in modern societies due to progressive cultural heterogeneity and migrations, which is the case of Portugal.

The authors undertake a revision of this topic in the literature

In a global picture Mental Disorders tend to be more prevalent in geographical contexts of poverty and that amazingly rich specificities are found throughout all psychiatric conditions, including suicidal behaviour, psychotic disorders, affective and anxiety related disorders, among many others, in what concerns ethnic and religious variability within countries, urban/rural environment and social status. It is now accepted that individuals with different ethnic and ancestral backgrounds might differ significantly in their biological inheritance, including pharmacological responses with its implications in therapeutic range and adverse effects.

It is imperative to take into account all these aspects in every society in order to adequately assess and treat psychiatric patients and ultimately achieve the real meaning of Modern Psychiatry.