Association of obesity to reaction time and visual memory in schizophrenia.

Background: Both overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders. Aims: Our aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder. Methods: The study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory. Results: Obesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures. Conclusions: The results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.

Association of somatic comorbidity and treatment adherence in patients with psychotic disorder.

BACKGROUND: Increased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. METHODS: Cross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients' adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. RESULTS: Patients' somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. CONCLUSION: This study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations.

Daily functioning and symptom factors contributing to attitudes toward antipsychotic treatment and treatment adherence in outpatients with schizophrenia spectrum disorders.

BACKGROUND: Poor adherence and negative attitudes to treatment are common clinical problems when treating psychotic disorders. This study investigated how schizophrenia core symptoms and daily functioning affect treatment adherence and attitudes toward antipsychotic medication and to compare patients using clozapine or other antipsychotics. METHOD: A cross-sectional study with data from 275 patients diagnosed with schizophrenia spectrum disorder. Patients adherence, attitudes, insight and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment scale. Overall symptomology was measured using the Brief Psychiatric Rating Scale (BPRS), the Health of the Nation Outcome Scale (HoNOS). The functioning was assessed using activities of daily living scale, instrumental activities of daily living scale and social functioning of daily living scale. RESULTS: Self-reported treatment adherence was high. Of the patients, 83% reported using at least 75% of the prescribed medication. Having more symptoms was related with more negative attitude towards treatment. There was a modest association with functioning and treatment adherence and attitude toward antipsychotic treatment. Attitudes affected on adherence in non-clozapine but not in clozapine groups. CONCLUSION: Early detection of non-adherence is difficult. Systematic evaluation of attitudes toward the treatment could be one way to assess this problem, along with optimized medication, prompt evaluation of side effects and flexible use of psychosocial treatments.

Changes in interleukin-6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression.

OBJECTIVE: Interleukin-6 (IL-6) has been reported to be elevated in major depressive disorder (MDD) but decreased by antidepressive medication. IL-6 levels are markedly elevated both after epileptic seizures and single electroconvulsive therapy (ECT) session, but long-term changes in IL-6 levels after ECT have not been studied. The correlation between immediate and long-term changes in proinflammatory cytokines and outcome after ECT was investigated. METHOD: Thirty patients suffering from MDD participated in the study. IL-6, interleukin-1ß (IL-1ß) and interleukin-1 receptor antagonist (IL-1RA) levels were examined at baseline and at 2 and 4 h after the first, fifth and the last ECT sessions. The response to ECT was measured with Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: ECT repeatedly caused an increase in IL-6 levels at the 4-h time point. However, the baseline IL-6 levels decreased among remitters, but not among non-remitters, towards the end of ECT. IL-1ß levels were mostly below detectable level, and IL-1Ra levels did not change during and after ECT. CONCLUSION: ECT has distinct acute and long-term effects on IL-6 levels. Interestingly, the long-term effect of ECT on IL-6 seems to correlate with outcome, providing further evidence of the mechanism of action of ECT and supporting the inflammation theory in MDD.

Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients. SUBJECTS AND METHODS: Associations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment. RESULTS: The serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P=0.078). CONCLUSIONS: Serum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.

The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response.

Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. The top association result in the meta-analysis of response represents SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Temperament profiles, major depression, and response to treatment with SSRIs in psychiatric outpatients.

OBJECTIVE: The Temperament and Character Inventory (TCI) is commonly used in adult populations. Our aim was to explore: (1) if there are specific differences in temperament dimensions related to depression in comparison with general population, (2) if the treatment response during the acute phase of major depressive disorder (MDD) is predictable by TCI temperament dimensions. METHOD: Temperament profiles in 98 MDD patients were compared with a Finnish community sample. The patients were treated with serotonin selective reuptake inhibitors (SSRIs) for 6 weeks and their temperament profiles were assessed at baseline and endpoint. The harm avoidance (HA) and depression scores at baseline and endpoint were modelled with path analysis. For path modelling, we tested the relationships between different temperament dimensions and depression symptoms and other clinical variables with Mancova model. RESULTS: The HA scores were significantly higher in patients both at baseline and endpoint compared to the Northern Finland 1966 Birth Cohort (NFBC). The patients, and especially males, had slightly higher reward dependency (RD) scores. HA at endpoint explained moderately the Montgomery Åsberg Depression Rating Scale (MADRS) endpoint score. HA endpoint score was strongly explained by HA baseline score. CONCLUSIONS: HA is associated with risk of and treatment response to depression.

RGS4 genotype is not associated with antipsychotic medication response in schizophrenia.

The aims of the present study were to compare the allele frequencies of a common single nucleotide polymorphism located upstream of the regulator of G-protein signaling 4 (RGS4) gene (T > G, Rs 951436) in 219 Finnish patients with schizophrenia and in 389 control subjects, to analyze corresponding frequencies between two different subtypes of 93 schizophrenia patients according to their medication response, and to study the effect of this SNP on age at onset in schizophrenia. The RGS4 (T > G, Rs 951436) genotype was not associated with incidence or age at onset in schizophrenia. Neither was the RGS4 genotype associated with medication response with two different subpopulations with schizophrenia.

Lack of association between two polymorphisms of brain-derived neurotrophic factor and response to typical neuroleptics.

Several studies have connected brain-derived neurotrophic factor (BDNF) with treatment response to neuroleptics. In recent studies, the BDNF expression was reduced by typical neuroleptics. We conducted a retrospective study on 94 patients with schizophrenia and 98 controls. The BDNF G196A and C270T polymorphisms are not associated with treatment response to typical neuroleptics or with age at first hospitalization. Moreover, these polymorphisms of the BDNF gene are not associated with the risk of schizophrenia.

Four-year outcome in non-compliant schizophrenia patients treated with or without home-based ambulatory outpatient care.

Non-compliance in neuroleptic maintenance treatment is a major concern in schizophrenia. Home-based outpatient care has been shown both to improve medication compliance and reduce relapse frequency. We analysed the need for hospitalisation, levels of functioning and mortality rate during the de-institutionalisation process in 41 schizophrenia patients with repeated hospitalisations and prolonged history of non-compliance. Eighteen of the patients received ambulatory outpatient care (AOC) after discharge. This treatment procedure focuses on enduring neuroleptic maintenance treatment. One of the hospital nurses takes care of home visits every 2-4 weeks. In the 4-year follow-up, half of the patients in the AOC group did not need hospitalisation at all and the number of days of hospitalisation in the whole group diminished by almost four-fifths compared with the previous 4 years. In the non-AOC group, there was a more limited decrease in the number of days of hospitalisation during the corresponding follow-up period. The mortality rates showed a slight tendency towards a better outcome in the AOC group. There was no change in the levels of functioning in the AOC group. This treatment can be carried out with limited resources. It clearly reduces the need for hospitalisation in a subgroup of schizophrenia patients having problems with compliance and recurrent relapse. The effectiveness of AOC on the mortality rates of schizophrenia patients needs further examination.

The reliability of compliance assessments performed by doctors and patients during neuroleptic treatment: a comparison of compliance ratings.

OBJECTIVE: To compare compliance assessments made by doctors and patients during neuroleptic drug treatment and to detect any variables explaining the discrepancies between their ratings. METHOD: Compliance reports regarding neuroleptic medication were collected from 100 in-patients and out-patients and from their doctors. Re-ratings were performed after 1-2 weeks. Compliance ratings were compared with demographic, treatment and symptom-related variables and with the Attitudes to Neuroleptic Treatment (ANT) questionnaire using logistic regression analysis. RESULTS: The doctors' and patients' compliance ratings showed good test-retest reliability (r=0.80, doctors; r=0.81, patients) and concordance (79% of the cases within the limits of +/-25%-units deviation). Variables explaining discrepancies between the ratings included female gender, a low level of education, the diagnosis of mania, a high neuroleptic dose and several items from the ANT scale. CONCLUSION: Manic episodes, negative attitudes to neuroleptic medication and a high-dose treatment increase the risk for deviating views of compliance in the doctor-patient relationship.

Attitudes towards neuroleptic treatment: reliability and validity of the attitudes towards neuroleptic treatment (ANT) questionnaire.

Non-compliance problems may rise to 50% among patients undergoing neuroleptic treatment. There are no direct measures available to predict compliance, if previous non-compliance is not taken into account. Attitudes towards neuroleptic treatment and insight into psychotic symptoms may vary during the course of the treatment process. It would be relevant to evaluate these items before taking any clinical action and later reassess the degree of change. The instrument thus far available has been the Drug Attitude Inventory. It has limitations for use with first-episode-patients and their follow-up. Its statements are dichotomous, which makes it difficult to determine the variation of attitudes e.g. during maintenance treatment, and most of the items concentrate on the subjective state of the patient, leaving attitudes as a minority in the scale. In this study, we report the new Attitudes towards Neuroleptic Treatment (ANT) questionnaire for the quantitative assessment of attitudes. We developed 10 statements for attitudes and two items for insight in the Visual Analogue Scale form (0-100 points). These were compared with the Drug Attitude Inventory 10 Questionnaire (DAI-10) (Hogan, T. P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol. Med. 13, 177-183.) among 106 subjects receiving neuroleptic medication. The 12 Visual Analogue Scales showed a high inter-item consistency and fair test-retest validity. The results were in accordance with the DAI-10. The scales comprised three factors: general attitudes, subjective feeling and expectations and insight. Attitudes towards neuroleptic treatment and insight into psychotic symptoms are different dimensions and can be measured quantitatively. The Attitudes towards Neuroleptic Treatment scale is useful in assessing the state of attitudes before starting medication and for follow-up among patients receiving neuroleptic medication.

Compliance in psychoses.

OBJECTIVE: To review the literature on compliance in psychoses and to evaluate the significance of the different compliance components presented. METHOD: Different definitions of the term compliance were first gathered. A search covering the years 1974-1997 was conducted in Medline and PsycLit databases using the keywords 'schizophrenia' or 'psychosis' and 'compliance'. The studies that took compliance into account as a separate variable were collected for further analysis. RESULTS: Unpleasant side-effects of medication, attitudes towards medication, delusional symptoms, substance abuse, insight, and supportive family environment were found to have the strongest correlation with compliance. The influence of cognitive impairment is not clearly proven. Integrated, cognitive-behavioural and psychoeducational treatment models include several methods to improve therapeutic alliance and compliance. CONCLUSION: As the majority of the studies have concentrated on neuroleptic treatment, the medication-related factors are best documented. In clinical practice, treatment compliance is based on patient-related, medication-related and interactional factors, such as treatment model and therapeutic alliance. Difficulties with insight and cognitive functioning are specific patient-related factors in the treatment of psychoses.