Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study.

OBJECTIVE: Individuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. METHODS: Cross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. RESULTS: Patients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86-17.27). CONCLUSION: Patients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.

Symptom Remission and Brain Cortical Networks at First Clinical Presentation of Psychosis: The OPTiMiSE Study.

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.

Remission from antipsychotic treatment in first episode psychosis related to longitudinal changes in brain glutamate.

Neuroimaging studies in schizophrenia have linked elevated glutamate metabolite levels to non-remission following antipsychotic treatment, and also indicate that antipsychotics can reduce glutamate metabolite levels. However, the relationship between symptomatic reduction and change in glutamate during initial antipsychotic treatment is unclear. Here we report proton magnetic resonance spectroscopy (1H-MRS) measurements of Glx and glutamate in the anterior cingulate cortex (ACC) and thalamus in patients with first episode psychosis (n = 23) at clinical presentation, and after 6 weeks and 9 months of treatment with antipsychotic medication. At 9 months, patients were classified into Remission (n = 12) and Non-Remission (n = 11) subgroups. Healthy volunteers (n = 15) were scanned at the same three time-points. In the thalamus, Glx varied over time according to remission status (P = 0.020). This reflected an increase in Glx between 6 weeks and 9 months in the Non-Remission subgroup that was not evident in the Remission subgroup (P = 0.031). In addition, the change in Glx in the thalamus over the 9 months of treatment was positively correlated with the change in the severity of Positive and Negative Syndrome Scale (PANSS) positive, total and general symptoms (P<0.05). There were no significant effects of group or time on glutamate metabolites in the ACC, and no differences between either patient subgroup and healthy volunteers. These data suggest that the nature of the response to antipsychotic medication may be related to the pattern of changes in glutamatergic metabolite levels over the course of treatment. Specifically, longitudinal reductions in thalamic Glx levels following antipsychotic treatment are associated with symptomatic improvement.

Patterns of recovery course in early intervention for FIRST episode non-affective psychosis patients: The role of timing.

BACKGROUND: Prevention of symptom relapse and promotion of functional recovery are the two main goals of early intervention following a first episode of non-affective psychosis (FEP). The identification of patterns of recovery is important in developing and implementing recovery focused interventions at set time interval. METHOD: Patterns of recovery course, in terms of symptomatic and functional remission, were explored at 1 and 3-year follow-up in a sample of 373 consecutive FEP patients. Relapses during this period were considered. RESULTS: Four patterns of recovery course were defined: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery were more likely have less severe baseline negative symptoms (OR = 2.092; 95% CI = 0.99-4.419) and to not be diagnosed with schizophrenia (OR = 2.242; 95% CI = 1.015-4.954). Short DUP (OR = 2.152; 95% CI = 0.879-5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954-5.457) increased the likelihood of good unstable recovery. Less severe baseline negative symptoms (OR = 3.851; 95% CI = 1.422-10.435) and single status (OR = 4.307; 95% CI = 1.014-18.293) increased the likelihood of a poor unstable recovery. Poor unstable pattern was significantly associated with a high relapse rate (73%). CONCLUSIONS: Our results shed light on identifying different recovery patterns in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly in reference to the role of timing in the design of interventions.

A pre-post pilot study of electronic cigarettes to reduce smoking in people with severe mental illness.

BACKGROUND: Smoking is the largest single contributor to poor physical health and increased mortality in people with serious mental illnesses. The aim of the study was to investigate the utility of electronic cigarettes (e-cigarettes) as a harm reduction intervention in this population. METHOD: Fifty tobacco smokers with a psychotic disorder were enrolled onto a 24-week pilot study (ClinicalTrials.gov: NCT02212041) investigating the efficacy of a 6-week free e-cigarette intervention to reduce smoking. Cigarette and e-cigarette use was self-reported at weekly visits, and verified using carbon monoxide tests. Psychopathology, e-cigarette acceptability and adverse effects were assessed using standardised scales. RESULTS: There was a significant (⩾50%) reduction in cigarettes consumed per day between baseline and week 6 [F(2.596,116.800) = 25.878, p < 0.001], and e-cigarette use was stable during this period [F(2.932,46.504) = 2.023, p = 0.115]. These changes were verified by significant carbon monoxide reductions between these time points [F(3.335,126.633) = 5.063, p = 0.002]. CONCLUSIONS: The provision of e-cigarettes is a potentially useful harm reduction intervention in smokers with a psychotic disorder.

Non-adherence to antipsychotic medication in first-episode psychosis patients.

This study evaluated the influence of attitudes and beliefs towards antipsychotics on adherence, and aimed to understand how satisfaction with information impacts adherence in first-episode psychosis. Fifty randomly selected out-patients attending the COAST Early Intervention service completed a survey comprised of the Selwood Compliance Scale, Beliefs about Medicines Questionnaire, and the Satisfaction with Information about Medicines Scale. Thirty-four percent of patients reported non-adherence to antipsychotic medication, and they were significantly younger than adherent patients. Adherent patients were more satisfied with medication information than non-adherent patients (65.7% and 34.3% respectively), suggesting that providing better information about antipsychotics may improve adherence.

Effectiveness of automated appointment reminders in psychosis community services: a randomised controlled trial.

We report on the first open-label, parallel group randomised controlled trial of automated appointment reminders in a psychosis community service in the UK. Ninety-five patients were randomly allocated to receiving/not receiving automated messaging reminders 7 days and 1 day before appointments. All 'Attended' and 'Missed' appointment outcomes over 6 months were analysed using cluster regression analysis. Reminded appointments were significantly more frequently attended than non-reminded appointments (unadjusted odds ratio (OR) = 3.54, 95% CI 1.36-9.22, P = 0.01; adjusted OR = 2.95, 95% CI 1.05-8.85, P < 0.05). Automated messaging reminders can provide a robust strategy for promoting engagement with psychosis services. Declaration of interest The authors have no competing financial interests to declare in relation to the current work. Sarah McAllister was supported by a King's Undergraduate Research Fellowship.

Who needs AESOP? Predicting long-term readmission rates from routine Early Intervention team discharge information.

AIM: Prognosis following early psychosis is highly variable. Long-term prognostic information from research studies is available in only a few areas. We sought to understand how well routine discharge information allows prediction of long-term readmission prognosis. METHODS: We reviewed the records of 239 people leaving Early Intervention services, after an average of 2.5 years, and counted the number of relapses. The distribution was modelled and extrapolated to a predicted 10 year outcome. Model predictions were compared with published data. RESULTS: Numbers of relapses varied substantially, with 59% having no relapses before discharge, and 5% having 4 or more. Model predictions for 10-year outcome were close to the observed data. CONCLUSIONS: A simple model can describe the distribution of numbers of relapses among people discharged from EI services, and predict long-term outcomes matching those observed in formal research. This low-cost approach could allow EI services to develop locale-specific prognostic information.

Tobacco smoking and its association with cognition in first episode psychosis patients.

Available evidence suggests that nicotine may enhance cognitive functioning. Moreover, it has been suggested that the high prevalence of smoking in people with schizophrenia is in part due to self-medication behaviour to alleviate cognitive deficits. We assessed the association between tobacco smoking and cognitive functioning in a large population of first episode psychosis (FEP) patients (n=304) and healthy controls (n=156). Smokers were not tobacco deprived, or were minimally deprived (≤2h). Verbal memory, visual memory, working memory, processing speed, executive function, motor dexterity and attention were assessed. The smoking prevalence among the FEP group was 57% (n=174). The age at which patients began smoking cigarettes regularly was 16.2years (SD=3.1), an average of 12years before experiencing the first frank symptoms of psychosis (age of onset=28.8; SD=9.3). The number of cigarettes smoked per day was 19.6 (SD=9.4), significantly more than healthy controls [11.0 (SD=7.6); p<0.001]. ANCOVA analysis did not show any significant difference between smokers and non-smokers in in the performance of any of the cognitive tasks in the FEP group or in the healthy control group, independent of gender, age, education or premorbid IQ. This suggests chronic exposure to nicotine through cigarette smoking is not associated with cognitive functioning in first-episode psychosis. These findings do not support the nicotine self-medication hypothesis as a contributor to the high prevalence of smoking among individuals suffering from serious mental illness.

Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis.

INTRODUCTION: The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment. MATERIAL AND METHODS: One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment. RESULTS: After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment. CONCLUSION: We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

Effects of aripiprazole, quetiapine and ziprasidone on plasma prolactin levels in individuals with first episode nonaffective psychosis: Analysis of a randomized open-label 1year study.

RATIONALE: Hyperprolactinemia is considered a troubling adverse effect of antipsychotics. Direct comparisons among second generation antipsychotics are scant in clinical practice. We hypothesize prolactin-sparing second-generation antipsychotics may have differential effects on prolactin levels and that they may be influenced by sex. OBJECTIVES: To explore the differential effect of three widely used prolactin-sparing antipsychotics, aripiprazole, quetiapine and ziprasidone, on prolactin plasma levels in first episode non-affective psychosis during a 1year of treatment. METHOD: From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. 141 patients who were randomly allocated to aripiprazole (N=56), quetiapine (N=36) or ziprasidone (N=49) were analyzed. The main outcome was differences in prolactin plasma levels over 1year follow-up among the three antipsychotics. Prolactin levels had a skewed distribution and therefore they were log-transformed before statistical analyses. RESULTS: Male patients on aripiprazole had a lower risk of suffering an increase on prolactin plasma levels (N=71; F=12.645; p<0.001). There was a gender effect with smaller changes in mean prolactin values only in males. Aripiprazole had a reduced risk of hyperprolactinemia (aripiprazole 19.6%) compared to quetiapine (44.4%) and ziprasidone (32.7%) (p=0.038); and quite similar findings were found when investigating males (p=0.040). No significant differences were found in females. The percentages of mild prolactin excess were: 14.3% on aripiprazole, 36.1% on quetiapine and 18.4% on ziprasidone (χ2=6.611 p=0.037). CONCLUSIONS: Our findings provide additional evidence of differential effects of three sparing-prolactin antipsychotics on prolactin release and may help clinicians to decide among therapeutic options.

The effects of tobacco smoking on age of onset of psychosis and psychotic symptoms in a first-episode psychosis population.

BACKGROUND AND AIMS: Research suggests that tobacco smokers may develop psychosis at an earlier age than non-smokers, with effects on psychotic symptoms. We aimed to test the difference in age of onset of psychosis between smokers and non-smokers. DESIGN: Self-report data were collected from smokers and non-smokers in a population of first-episode psychosis patients. SETTING: Out-patient first-episode psychosis programme in Santander (Cantabria), Spain. PARTICIPANTS: Three hundred and ninety-seven patients (226 male, 171 female) who agreed to take part between 2001 and 2011. MEASUREMENTS: Age of onset of psychosis, age of smoking initiation, demographics, family history of psychosis and cannabis use were collected by self-report. FINDINGS: Kaplan-Meier analysis showed that smokers had a significantly lower mean age of psychosis onset [smokers = 27.4 (± 8.1) years, non-smokers = 30.5 (± 9.9) years] than non-smokers (χ2(1)  = 11.72, P = 0.001). The Cox proportional hazard model showed no significant difference in the age of psychosis onset between smokers and non-smokers adjusted for covariates [hazard ratio (HR) = 1.034, 95% confidence interval (CI) = 0.828-1.291]. Age of psychosis onset was predicted significantly by cannabis use (HR = 2.073, 95% CI = 1.633-2.633) and gender (HR = 1.706, 95% CI = 1.363-2.135). CONCLUSIONS: Smokers do not appear to have a significantly earlier age of psychosis onset than non-smokers after taking into account cannabis use and gender.

Suicidal behaviour in first-episode non-affective psychosis: Specific risk periods and stage-related factors.

Suicide is a major cause of premature death in psychosis. Earlier stages have been associated with higher risk. However, such risk periods have not been specifically determined and risk factors for suicidal behaviour may change over those periods, which may have crucial implications for suicide prevention. The aim of this study was to determine and characterize the highest risk period for suicide in a representative sample of first-episode psychosis (FEP) patients. Suicidal behaviour prior to first presentation of psychosis and during a 3-year follow-up was examined in a sample of 397 individuals. Risk factors for suicidal behaviour during specific time periods were investigated and compared. The greatest suicide risk was found during the month before and 2 months after first contact with psychiatric services (i.e., 'early' attempts). Severity of depressive symptoms and cannabis use emerged as predominant risk factors across time. 'Early' attempters were characterized as being male, living in urban areas, having poor premorbid adjustment, requiring hospitalization, scoring higher on anxiety measures and unusual thought content than non-attempters. Greater suspiciousness and more severe depressive symptoms distinguished the 'late' attempters. In conclusion, there is a specific high risk period for suicide in FEP around the time of the first presentation. Early intervention programmes targeting phase-specific risk factors, particularly psychotic symptoms management and secondary depression prevention strategies may be useful for suicide prevention in psychosis.

Dysbindin gene variability is associated with cognitive abnormalities in first-episode non-affective psychosis.

INTRODUCTION: Dystrobrevin-binding protein 1 gene (dysbindin or DTNBP1) has been associated with schizophrenia and cognitive performance. Its expression in areas implicated in cognition such as the dorsolateral prefrontal cortex, as well as its role in dopaminergic and glutamatergic system, has been replicated by several studies. The main aim of this study was to examine the association between DTNBP1 variability and cognitive performance in a sample of 238 patients with a first episode of a non-affective psychosis. METHODS: Patients, and a comparison sample of 47 healthy subjects, completed an extensive neuropsychological battery. Five single nucleotide polymorphisms (SNPs) within DTNBP1 (rs2619528, rs2619538, rs3213207, rs2619539 and rs760761) and three haplotypes (GACAC, GAGAC and GTGAC) were analysed. RESULTS: In the group of patients, we found a significant association between two of the DTNBP1 SNPs and one of the haplotypes (rs2619539, rs3213207 and GACAC) and a measure of premorbid IQ [Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III) Vocabulary subtest]. Moreover, one of these SNPs, rs2619539, was also associated with our measure of working memory (WAIS-III Backward digits subtest) and two haplotypes, GAGAC and GTGAC, with our measure of verbal memory (Rey Auditory Verbal Learning Test), of visual memory (Rey Complex Figure Test) in the case of GAGAC, and of speed of processing (WAIS-III Digit Symbol-coding) in the case of GTGAC. CONCLUSIONS: Our findings add further evidence suggesting an association between dysbindin gene variability and cognitive abnormalities in schizophrenia, providing preliminary evidence of this association since the time of illness onset among minimally medicated patients.

Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis.

This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3 months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2 kg [SD=4.1] versus 4.3 kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.

Lack of insight 3 years after first-episode psychosis: an unchangeable illness trait determined from first presentation?

BACKGROUND: Lack of insight is recognized as a symptom that predisposes the individuals with psychosis to noncompliance with the treatment, leading to poorer course of illness. This study aimed to explore baseline predictors of disturbances on insight at follow-up. METHODS: Three insight dimensions (insight of: 'mental illness', 'need for treatment' and 'the social consequences of the disorder') were measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) in a cohort of 224 first-episode psychosis (FEP) patients at 3-year follow-up. Subgroups, good vs. poor insight, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. Regression models tested baseline predictors for each insight dimension. RESULTS: At 3-year follow-up a high percentage of patients, 45%, 36% and 33% for each dimension, were found to remain lacking insight. Poor insight into having an illness was predicted by a diagnosis of schizophrenia and poor baseline insight of the social consequences; insight into the need for treatment was predicted by adolescent adjustment and depression at baseline; and insight into the social consequences of the disorder was determined by late adolescent adjustment and baseline insight of mental illness. CONCLUSIONS: Our findings support the hypothesis that long-term insight in psychosis seems to be, to some extent, determined from first presentation, showing trait-like properties. A subgroup of 'lacking insight' patients, which is characterized by a diagnosis of schizophrenia, lower levels of premorbid adjustment and less severe depressive symptoms at baseline might benefit from special interventions targeted at enhancing insight from their first contact with psychiatric services.

Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year.

RATIONALE: Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment. OBJECTIVES: The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year. METHOD: From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants. CONCLUSIONS: First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.

Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors.

Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.