[Dietary intake of young Icelanders with psychotic disorders and weight development over an 8-12 months period].

INTRODUCTION: The prevalence of lifestyle related diseases is higher among people with psychotic disorders than the general population. The aim was to assess dietary intake of young people with psychotic disorders for the first time in Iceland. MATERIAL AND METHODS: Subjects were young people (n=48, age 18-30y) with psychotic disorders. Dietary intake was assessed by a 24-hour recall in July-August 2016, and compared with official recommendations and intake of the general public (n=250, age 18-30y). Body weight in the past eight to 12 months, was retrieved from medical records. RESULTS: Consumption of fruits, fish, dairy products, vegetable and fish oil was significantly lower among subjects when compared with the general public, while their soft drink and sweets consumption was higher (p<0.001). Furthermore, the contribution of added sugar was higher (15E% vs. 12E%) and protein intake lower (16E% vs. 18E%). Consumption of omega-3 fatty acids and vitamin D was lower among subjects than the general public and lower than recommended (0.04±0.3% omega-3 of total energy vs. 1.2±0.6%, p<0.001 and 3.1±4.2 µg vitamin D/day vs. 5.6±6.5 µg/day, p<0.001). Almost 40% of the subjects had gained >5% of their initial body weight in the past 8-2 months. CONCLUSION: Diet of young people with psychotic disorders is not consistent with recommendations and is worse than the diet of their peers in the general population. It is important to find ways to improve the diet and thereby nutrient intake of the group. Key words: psychotic disorders, schizophrenia, recommended dietary allowances, fatty acids, omega-3, vitamin D. Correspondence: Ingibjorg Gunnarsdottir, ingigun@landspitali.is.

Risk of diabetes and dyslipidemia during clozapine and other antipsychotic drug treatment of schizophrenia in Iceland.

BACKGROUND: Type 2 diabetes (T2D) and raised blood lipids are associated with the use of antipsychotics, not least clozapine. AIMS: To describe the prevalence of high blood glucose levels, T2D, and dyslipidemia, in association with the use of clozapine or other antipsychotics in patients with schizophrenia in Iceland. METHOD: This study identified 188 patients treated with clozapine and 395 patients never treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital. The comparison group consisted of Icelandic population controls. Data were obtained on blood glucose, HbA1c, and blood lipid levels from these health records. RESULTS: The prevalence of T2D was 14.3% in the clozapine group, where the mean age was 51.2 years, and 13.7% in the never-on-clozapine group, where the mean age was 58.6 years. Males on clozapine were 2.3-times more likely and females 4.4-times more likely to have developed T2D than controls from an age-adjusted Icelandic cohort, while males on other antipsychotics were 1.5-times more likely and females 2.3-times as likely to have T2D than controls. Only one case of ketoacidosis was identified. Triglyceride levels were significantly higher in both treatment groups compared to controls in the age-adjusted Icelandic cohort. CONCLUSIONS: Clinicians must take active steps to reduce the risk of T2D and raised triglycerides in patients with schizophrenia. Antipsychotics were associated with a greater risk of T2D developing in females compared to males.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

BACKGROUND: Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. METHODS: The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. RESULTS: The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. CONCLUSIONS: Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

BACKGROUND: Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized. AIMS: To evaluate the initiation and discontinuation of clozapine at Landspitali University Hospital in Iceland and the prevalence of antipsychotic polypharmacy in clozapine-treated patients. METHODS: The study is a part of an ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients on clozapine or who have been on clozapine by using a keyword search in the electronic health records and by reviewing their medical records. RESULTS: Mean age at first treatment with clozapine was 37.8 years. Mean follow-up period on clozapine was 11 years. After 20 years of treatment 71.2% of patients were still on clozapine. After one year of treatment 84.4% of patients were still receiving clozapine treatment. We estimate that 11.4% of patients with schizophrenia in Iceland are taking clozapine and that 16% have been treated with clozapine at some point. Polypharmacy is common, since nearly 2/3, 65.6%, of patients taking clozapine use at least one other antipsychotic and 16.9% are also receiving depot injections. CONCLUSIONS: We need to increase the awareness of psychiatrists in Iceland with regard to treatment with clozapine, since only about half of the estimated population of patients with treatment-resistant schizophrenia in Iceland have ever been treated with clozapine. Nearly two thirds of patients who are prescribed clozapine in Iceland remain on it long-term.

Neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends on history of psychosis rather than diagnostic group.

OBJECTIVES: Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends more on history of psychosis than diagnostic category or subtype. METHODS: A sample of individuals with schizophrenia (n=102), schizoaffective disorder (n=27), and bipolar disorder (I or II) with history of psychosis (n=75) and without history of psychosis (n=61) and healthy controls (n=280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. RESULTS: Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample, history of psychosis explained more of the neurocognitive variance than bipolar diagnostic subtype. CONCLUSIONS: Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.

Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level.

Medication nonadherence in severe mental disorders is an important clinical issue, but estimates vary between studies. There is a need for valid self-reports for both research and clinical practice. This study examined the level of adherence to prescribed medication in outpatients with severe mental disorders and evaluated the validity of a simple self-report rating of adherence. From an ongoing study of severe mental disorders, 280 patients with schizophrenia and bipolar disorder who were prescribed psychopharmacological agents were included. We assessed adherence with serum concentration of medicines and tested the sensitivity and specificity of a simple self-report questionnaire for patients and compared with a report from health personnel. Adherence rate defined by serum concentrations within reference level was 61.6% in the total sample, 58.4% for schizophrenia and 66.3% for bipolar disorder. The patients' self-report scores overestimated adherence, but correlated significantly to health personnel scores (r = 0.50) and to serum concentration of medication (r = 0.52); the positive predictive value was 70%, and the negative predictive value was 91%. In this naturalistic sample, outpatients with severe mental disorders showed relatively good adherence to prescribed medication, and self-report questionnaires seem to be a valid method for measuring adherence.

Delusions are associated with poor cognitive insight in schizophrenia.

The purpose of the study was to investigate the relationship between the symptoms delusions and hallucinations measured by the Positive and Negative Syndrome Scale and cognitive insight as assessed with the Beck Cognitive Insight Scale (BCIS) in patients with schizophrenia. The BCIS is based on 2 subscales, self-reflectiveness and self-certainty, measuring objectivity, reflectiveness and openness to feedback, and mental flexibility. Overall cognitive insight was defined as the difference between self-reflectiveness and self-certainty. This cross-sectional study of 143 patients showed that the occurrence of delusions is associated with low self-reflectiveness and high self-certainty, reflecting low cognitive insight. Hallucinations in the absence of delusions were associated with high self-reflectiveness and low self-certainty, possibly reflecting more open-mindedness and higher cognitive insight. The present findings suggest that delusions are associated with low cognitive insight, whereas solitary hallucinations may be associated with high cognitive insight.

Using the Wisconsin Card Sorting Test to assess learning potential in normal IQ schizophrenia: does it have potential?

BACKGROUND: Learning potential, a dynamic multi-administration approach to assessment, is claimed to predict functional outcome in schizophrenia better than traditional single-administration neuropsychological tests. AIMS: This study investigates the relation between learning potential and clinical and demographic variables, social functioning and neuropsychological abilities in a sample of 30 participants with schizophrenia with a mean IQ score within the normal range (mean Wechsler Abbreviated Scale of Intelligence (WASI) IQ=106). METHODS: Two Wisconsin Card Sorting Test (WCST) based methods for assessing learning potential are compared. RESULTS: The dimensional approach (calculation of gain scores following training) identified one aspect of executive functioning (set shifting) to be related to learning potential. Associations with other neuropsychological tests and social functioning were however limited. The categorical approach (separating high-achievers from learners and non-learners) was not sensitive within this normal IQ sample. CONCLUSIONS: Although there seems to be a relation between learning potential and some aspects of executive functioning, the two existing WCST methods should be used with caution when assessing learning potential in individuals with schizophrenia who have IQ scores within the normal range.

Measurement of insight in patients with bipolar disorder: are self-rated scales developed for patients with schizophrenia applicable?

Our aim was to study if the Birchwood Insight Scale has acceptable psychometric properties when used for patients with bipolar disorders. Patients with schizophrenia (n = 101), bipolar I (n = 57), and bipolar II disorder (n = 37) completed the self-report scale. The items form 3 subscales, awareness of illness, relabeling of symptoms, and need for treatment. The total scale had good internal consistency for patients with schizophrenia, fairly good for bipolar I, but poor for bipolar II disorder. On subscale level the internal consistency was mostly marginal to poor for all patient groups. The level of insight was similar in schizophrenia and bipolar I disorder. The psychometric properties for the insight scale were poorer in bipolar disorders than in schizophrenia, and the scale did not work for patients with bipolar II disorder. This suggests a cautious use of the scale across different diagnostic groups.

Dyslipidemia independent of body mass in antipsychotic-treated patients under real-life conditions.

OBJECTIVE: Antipsychotic (AP) treatment, in particular with some second-generation drugs, is associated with weight gain and other metabolic side effects. However, the relationship between drug-induced weight gain and dyslipidemia is not well understood. We investigated how cardiometabolic risk factors were related to body mass during treatment with different APs under real-life conditions. METHODS: This cross-sectional naturalistic study included 242 subjects with severe mental disorders who were on monotherapy with olanzapine (OLZ) or clozapine (CLZ) (n = 80), monotherapy with other APs (n = 80), or unmedicated (n = 82). Groups were adjusted for age and compared for prevalence of the metabolic syndrome and its components. Groups were further adjusted for body mass and compared for mean values of blood pressure, lipids, and fasting glucose. RESULTS: There was no significant intergroup difference in the prevalence of metabolic syndrome, obesity, hypertension, or hyperglycemia. Despite similar body mass index, OLZ/CLZ-treated subjects had significantly higher prevalence of dyslipidemia (high triglyceride and low HDL cholesterol levels) than unmedicated subjects. They also had higher mean values of triglycerides (P = 0.003) and lower mean values of HDL cholesterol (P < 0.001). Patients treated with other APs had intermediate values. CONCLUSIONS: Intergroup differences in body mass index were minimal in this naturalistic setting, probably because of awareness of this treatment hazard among clinicians. However, independently of body mass, dyslipidemia was significantly associated with AP treatment, in particular with OLZ and CLZ. These findings indicate a primary effect of APs on lipid regulation, important in understanding their mechanism of action, and with clinical implications.

Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction.

OBJECTIVES: Studies on neurocognitive functioning in bipolar disorder, reporting deficits in memory, attention, and executive functioning, have primarily focused on bipolar I disorder. The aim of this study was to examine whether patients with bipolar I and bipolar II disorder have different neurocognitive profiles. METHODS: Forty-two patients with bipolar I disorder, 31 patients with bipolar II and 124 healthy controls, from a large ongoing study on psychotic disorders, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. RESULTS: The bipolar I group performed significantly poorer than the healthy control group and the bipolar II group on all measures of memory. Compared with the control group, the bipolar I group also had significantly reduced performance on most measures of attention and executive functioning, while the bipolar II group only had a significantly reduced performance on a subset of these measures. On average, 24% of the bipolar I group had clinically significant cognitive impairment (< or =1.5 SD below the control group mean) across measures, compared with 13% of the bipolar II group. CONCLUSIONS: Patients with bipolar I and bipolar II disorder in this study have different neurocognitive profiles. Bipolar I patients have more widespread cognitive dysfunction both in pattern and magnitude, and a higher proportion has clinically significant cognitive impairments compared with patients with bipolar II. This may suggest neurobiological differences between the two bipolar subgroups.

Increased expression of lipid biosynthesis genes in peripheral blood cells of olanzapine-treated patients.

Recent in-vitro studies show that antipsychotic drugs increase lipid biosynthesis through changes in gene expression. Based on these finding we compared the expression of two central lipid biosynthesis genes, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD), in whole blood of olanzapine-treated and unmedicated patients. Patients with psychotic disorders were consecutively selected from an ongoing, naturalistic study, and divided into two groups according to the following criteria: (1) strict monotherapy with olanzapine (n=19) or (2) no current medication (n=19). The groups were matched on gender, race and body mass index. Blood lipid levels were examined, and gene expression in whole blood was assessed with quantitative real-time PCR. Expression of FASN (p=0.003) and SCD (p=0.002) was significantly up-regulated in olanzapine-treated compared to unmedicated patients. Transcriptional activation of lipid biosynthesis genes in peripheral blood cells of olanzapine-treated patients suggests a direct lipogenic action of antipsychotic drugs, which may be related to metabolic adverse effects.

Emotion perception and learning potential: mediators between neurocognition and social problem-solving in schizophrenia?

Social cognition and learning potential have been proposed as mediating variables between neurocognition and functional outcome in schizophrenia. The present study examined this relation in a schizophrenia group (N = 26) with normal IQ. Neurocognition was measured with a composite score from tests of verbal learning, psychomotor speed, and executive functioning. Functional outcome was defined as social problem-solving skills and assessed with a role-play test. Social cognition was indexed by tests of visual and auditory emotion perception; and learning potential by estimating a gain score using a triple administration of the WCST. Neurocognition was confirmed to be a strong predictor of social problem-solving, and emotion perception was related to both neurocognition and social problem-solving. When controlling for emotion perception, the association between neurocognition and social problem-solving was weakened, implying a mediating role of emotion perception. Learning potential was not significantly related to neurocognition or social problem-solving, and thus not found to mediate the studied relation. In conclusion, our study indicates that emotion perception is a mediator between neurocognition and functional outcome as assessed with a social problem-solving task and thus a key factor in understanding functional outcome of schizophrenia.

Measuring cognitive insight in schizophrenia and bipolar disorder: a comparative study.

BACKGROUND: Beck Cognitive Insight Scale (BCIS) has been designed for assessment of self-reflection on patients' anomalous experiences and interpretations of own beliefs. The scale has been developed and validated for patients with schizophrenia. We wanted to study the utility of the scale for patients with bipolar disorder. The relationship between the BCIS as a measure of cognitive insight and established methods for assessment of insight of illness was explored in both diagnostic groups. METHODS: The BCIS self-report inventory was administered to patients with schizophrenia (n = 143), bipolar disorder (n = 92) and controls (n = 64). The 15 items of the inventory form two subscales, self-reflectiveness and self-certainty. RESULTS: The internal consistency of the subscales was good for the patient groups and the controls. The mean subscale scores were not significantly different for the three groups. Four items in subscale self-reflectiveness referring to psychotic experiences gave, however, different results in the control subjects. Self-certainty and scores on insight item PANSS correlated significantly in the schizophrenia, but not in the bipolar group. CONCLUSION: BCIS with its two subscales seems applicable for patients with bipolar disorder as well as for patients with schizophrenia. The self-report inventory can also be applied to control subjects if the items referring to psychotic experiences are omitted. In schizophrenia high scores on self-certainty is possibly associated with poor insight of illness. For the bipolar group the subscales are largely independent of traditional insight measures.

The level of cardiovascular risk factors in bipolar disorder equals that of schizophrenia: a comparative study.

OBJECTIVE: In schizophrenia, increased rates of somatic mortality have been shown to correspond with a high prevalence of cardiovascular risk factors, including smoking and the metabolic syndrome. In bipolar disorder, the amount of cardiovascular risk is still largely unknown. This study compares the prevalence of smoking and metabolic disturbances in bipolar disorder and schizophrenia in a representative sample of patients under naturalistic conditions. It also compares the prevalence of risk factors in each diagnostic group with the general population. METHOD: Longitudinal data on clinical groups from October 2002 through December 2005 were from the Oslo TOP Study (DSM-IV bipolar disorder [N = 110] and schizophrenia [N = 163]). Reference data were from the 2000 to 2001 Oslo Health Study (18,770 individuals of the same area). Background variables, prevalence of smoking, and age-adjusted levels of metabolic risk factors were compared between diagnostic groups. Risk factors in both groups were then compared with the general population. RESULTS: Patients with bipolar disorder had higher levels of education, better social functioning, fewer psychiatric symptoms, and less use of medication than patients with schizophrenia. There was no significant difference between diagnostic groups in the prevalence of smoking, obesity, metabolic syndrome, or diabetes. The mean level of high density lipoprotein cholesterol was lower in schizophrenia (p < .001), and systolic blood pressure was higher in bipolar disorder (p < .05). Both diagnostic groups had a prevalence of cardiovascular risk factors about twice that of the general population. CONCLUSION: The prevalence of cardiovascular risk factors was alarmingly high for bipolar disorder and schizophrenia patients compared with the general population, and the prevalence was approximately the same in both diagnostic groups.

Sociodemographic characteristics and cardiovascular risk factors in patients with severe mental disorders compared with the general population.

OBJECTIVE: To study the prevalence and distribution of cardiovascular risk factors in a group of patients with severe mental disorders compared with the general population and investigate if differences in sociodemographic background variables between groups were associated with differences in risk profile. METHOD: We compared data from the ongoing Ulleval 600 Study (205 pharmacologically stable outpatients with DSM-IV psychotic disorders) with data from the 2000-2001 Oslo Health Study (18,770 individuals from the general population of the same area). Subjects were stratified according to age and gender and compared for ethnic background, level of education, marital status, and prevalence of risk factors. RESULTS: Patients had an overall prevalence of smoking, obesity, hypertension, dyslipidemia, and diabetes mellitus about twice that of the reference group. Patients aged 18 through 50 years had the highest level of risk factors when compared with the general population. There was no major difference in ethnic background or educational level between cohorts. CONCLUSION: The increased cardiovascular risk profile in patients is particularly pronounced in young individuals and could not be explained by sociodemographic variables alone.