Predictors of treatment satisfaction in antipsychotic-naïve and previously medicated patients with acute-phase psychosis

Abstract

Background: Treatment satisfaction predicts treatment adherence and long-term outcome for patients with psychosis. It is therefore important to understand the underpinnings of patient satisfaction in psychosis treatment for optimal treatment delivery.

Aims: To examine the associations between satisfaction and level and change in positive symptoms, insight, depression and side effects of antipsychotics in previously medicated and antipsychotic-naïve patients.

Method: Data derive from a randomised trial, with 226 respondents at baseline and 104 at follow-up. The measures were the positive subscale and insight item from the Positive and Negative Syndrome Scale, Calgary Depression Scale, the UKU Consumer Satisfaction Rating Scale, and the UKU side effects scale. Structural equation modelling was used to test the model. The full information maximum likelihood estimator used all available data.

Results: In the sample of 226 patients, 67.3% were male and 44.2% were antipsychotic-naïve. The mean age was 34.1 years. For previously medicated patients, satisfaction was predicted by level of insight (b?=??2.21, β?=??0.42) and reduction in positive symptoms (b?=??0.56, β?=??0.39). For antipsychotic-naïve patients, satisfaction was predicted by level and change of insight (b?=??2.21, β?=??0.46), change in depression (b?=??0.37, β?=??0.26) and side effects (b?=??0.15, β?=??0.30). All predictors were significant at the 0.05 level.

Conclusion: Reducing positive symptoms and side effects are important to enhance patient satisfaction. However, improving insight and reducing depression are more important in antipsychotic-naïve patients.

Trial registration: ClinicalTrials.gov identifier: NCT00932529.     

Neural oscillations in antipsychotic-naïve patients with a first psychotic episode

Objectives: In chronic schizophrenic psychoses, oscillatory abnormalities predominantly occur in prefrontal cortical regions and are associated with reduced communication across cortical areas. Nevertheless, it remains unclear whether similar alterations can be observed in patients with a first episode of psychosis (FEP), a state characterised by pathological features occurring in both late prodromal patients and initial phases of frank schizophrenic psychoses. Methods: We assessed resting-state electroencephalographic data of 31 antipsychotic-naïve FEP patients and 29 healthy controls (HC). We investigated the three-dimensional (3D) current source density (CSD) distribution and lagged phase synchronisation (LPS) of oscillations across small-scale and large-scale brain networks. We additionally investigated LPS relationships with clinical symptoms using linear mixed-effects models. Results: Compared to HC, FEP patients demonstrated abnormal CSD distributions in frontal areas of the brain; while decreased oscillations were found in the low frequencies, an increase was reported in the high frequencies (P?<?0.01). Patients also exhibited deviant LPS in the high frequencies, whose dynamics changed over increasing 3D cortico-cortical distances and increasing psychotic symptoms. Conclusions: These results indicate that in addition to prefrontal cortical abnormalities, altered synchronised neural oscillations are also present, suggesting possible disruptions in cortico-cortical communications. These findings provide new insights into the pathophysiological mechanisms of emerging schizophrenic psychoses.     

Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis

Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-na?ve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.     

Metabolic syndrome in antipsychotic naïve patients diagnosed with schizophrenia

Aim: The article aims to study the prevalence of metabolic syndrome (MS) and subthreshold MS in antipsychotic naïve patients with schizophrenia. Materials and methods: Forty‐six antipsychotic naïve patients diagnosed with schizophrenia were evaluated for the presence of metabolic abnormalities using International Diabetes Federation and modified National Cholesterol Education Program – Third Adult Treatment Panel criteria. Results: Five patients (10.86%) fulfilled International Diabetes Federation criteria for MS and six patients (13.04%) met modified National Cholesterol Education Program – Third Adult Treatment Panel criteria for MS. Additionally, 14 (30.43%) more patients fulfilled 2 out of the 5 criteria for MS and another 19 (41.3%) fulfilled 1 criterion for MS. Of the 19 patients who fulfilled one criterion for MS, 18 had an abnormality other than increase in waist circumference. Conclusion: Findings of the present study suggest that although only few antipsychotic naïve patients diagnosed with schizophrenia have MS, a significantly large proportion of patients have subsyndromal MS. Awareness of this in clinicians can have implications in the selection of antipsychotic medication.     

Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders

Objective: Hyperprolactinaemia as a side effect of dopamine receptor blockers is common in patients with schizophrenia and other psychotic disorders and may lead to amenorrhoea, galactorrhoea, hypogonadism, subfertility and osteoporosis. The aim of our study was to determine whether hyperprolactinaemia occurs also in patients with schizophrenia and other psychotic disorders prior to any antipsychotic treatment.

Methods: Serum prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free tetraiodothyronine (FT4) and cortisol levels were measured in 40 newly diagnosed, drug naïve, patients with schizophrenia and other psychotic disorders and in 40 age and gender matched healthy subjects.

Results: The median prolactin value was 12.5?ng/ml (range: 2–38?ng/ml) for patients and 8.6?ng/ml (range: 4–17.6?ng/ml) for healthy subjects (p?=?0.011). Patients had lower levels of T3 compared to healthy controls (mean: 1.08?ng/ml, SD: 0.16 vs. 1.18?ng/ml, 0.18, respectively; p?=?0.008). Serum TSH, FT4 and cortisol levels were similar between the two groups. Multiple regression analysis revealed that the difference in serum prolactin values was independent of thyroid function (TSH, FT4, T3) and serum cortisol levels.

Conclusions: A higher serum prolactin level was found in drug naïve, newly diagnosed patients with schizophrenia and other psychotic disorders compared to healthy controls, prior to starting any antipsychotic treatment.     

Impaired temporoparietal deactivation with working memory load in antipsychotic-naïve patients with first-episode schizophrenia

Abstract

Objectives. Neuroimaging studies have shown abnormal task-related deactivations during working memory (WM) in schizophrenia patients with recent emphasis on brain regions within the default mode network. Using fMRI, we tested whether antipsychotic-naïve schizophrenia patients were impaired at deactivating brain regions that do not subserve WM. Methods. Twenty-three antipsychotic-naïve patients with first-episode schizophrenia and 35 healthy individuals underwent whole-brain 3T fMRI scans while performing a verbal N-back task including 0-back (no WM load), 1-back (low WM load), and 2-back (high WM load) conditions. Results. Contrasting the 2-back and 0-back conditions revealed that patients deactivated default mode network regions to a similar degree as controls. However, patients were impaired in deactivating large bilateral clusters centred on the superior temporal gyrus with increasing WM load. These regions activated with the no WM load condition (0-back) in both groups. Conclusions. Because 0-back activation reflects verbal attention processes, patients’ persistent activation in the 1-back and 2-back conditions may reflect an inability to shift cognitive strategy with onset of WM demands. Since patients were antipsychotic-naïve and task performance was equal to controls, we infer that this impaired temporoparietal deactivation may represent a primary dysfunction in schizophrenia.     

Abnormal glucose tolerance,white blood cell count,and telomere length in newly diagnosed,antidepressant-naïve patients with depression

Chronic mood disorders have been associated with a shortened telomere, a marker of increased mortality rate and aging, and impaired cellular immunity. However, treatment may confound these relationships. We examined the relationship of glucose tolerance, white blood cell count and telomere length to depression in newly diagnosed, antidepressant-naïve patients. Subjects with major depression (n = 15), and matched healthy control subjects (n = 70) underwent a two-hour oral glucose tolerance test and evaluation of blood cell count and telomere content. The depression group had significantly higher two-hour glucose concentrations and a lower lymphocyte count than control subjects (respective means [SD] for two-hour glucose were 125.0 mg/dL [67.9] vs 84.6 [25.6] (p < .001); for lymphocyte count 2.1 × 10⁹/L [0.6] vs 2.5 × 10⁹/L [0.7] p = .028). Telomere content was significantly shortened in the depression group (87.9 [7.6]) compared to control subjects (101.0 [14.3]; p < 0.01). Abnormal glucose tolerance, lymphopenia and a shortened telomere are present early in the course of depression independently of the confounding effect of antidepressant treatment, supporting the concept of major depression as an accelerated aging disease.     

Impairment of verbal memory and learning in antipsychotic-naïve patients with first-episode schizophrenia

BACKGROUND: Verbal memory deficits are of interest in schizophrenia because of the potential relationship to functional and anatomic mesial temporal lobe pathology in this disorder. The goal of this study was to characterize the nature of verbal memory impairments in antipsychotic-na?ve schizophrenic patients early in the course of illness. METHODS: Neuroleptic-na?ve patients with schizophrenia (n=62) and healthy individuals (n=67), matched on IQ, age, sex, and parental socioeconomic status, were administered the California Verbal Learning Test (CVLT). RESULTS: Schizophrenia participants performed significantly worse than healthy individuals on measures of verbal learning, short- and long-term memory, and immediate attention. Deficits in recall were related to reduced use of organizational strategies to facilitate verbal encoding and retrieval. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. Memory deficits had minimal relation to positive or negative symptom severity. CONCLUSIONS: Schizophrenia is characterized by significant verbal memory dysfunction early in the course of illness prior to treatment with antipsychotic medications. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate prefrontal dysfunction as a contributor to verbal memory deficits in schizophrenia.     

Pretreatment and longitudinal studies of neuropsychological deficits in antipsychotic-naïve patients with schizophrenia

The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified. A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period. A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points. At baseline, a generalized deficit across cognitive domains was evident for the schizophrenia sample. After 6 weeks of treatment, patients showed modest improvements in visual memory and visual perception, but a decline in verbal memory. Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period. Relatively static and generalized neuropsychological dysfunction, evident from illness onset, is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia.     

Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: A follow-up study in antipsychotic-naïve patients with first-episode psychosis

A study of the gene expression levels in the blood of individuals with schizophrenia in the beginning of the disease, such as first-episode psychosis (FEP), is useful to detect gene expression changes in this disorder in response to treatment. Although a large number of genetic studies on schizophrenia have been conducted, little is known about the effects of antipsychotic treatment on gene expression. The aim of the present study was to examine differences in the gene expression in the blood of antipsychotic-naïve FEP patients before and after risperidone treatment (N = 44) and also to verify the correlation with treatment response. In addition, we determined the correlations between differentially expressed genes and clinical variables. The expression of 40 neurotransmitter and neurodevelopment-associated genes was assessed using the RT² Profiler™ PCR Array. The results indicated that the GABRR2 gene was downregulated after risperidone treatment, but no genes were associated with response to treatment and clinical variables after Bonferroni correction. GABRR2 downregulation after treatment can both suggest an effect of risperidone treatment or processes related to disease progression, either not necessarily associated with the improvement of symptoms. Despite this change was observed in blood, this decrease in GABRR2 mRNA levels might be an effect of changes in GABA concentrations or other systems interplay consequently to D2 blockage induced by risperidone, for example. Thus, it is important to consider that antipsychotics or the progression of psychotic disorders might interfere with gene expression.     

Striatal volume abnormalities in treatment-naïve patients diagnosed with pediatric major depressive disorder

OBJECTIVE: The striatum, including the putamen and caudate, plays an important role in executive and emotional processing and may be involved in the pathophysiology of mood disorders. Few studies have examined structural abnormalities of the striatum in pediatric major depressive disorder (MDD) patients. We report striatal volume abnormalities in medication-na?ve pediatric MDD compared to healthy comparison subjects. METHOD: Twenty seven medication-na?ve pediatric Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) MDD and 26 healthy comparison subjects underwent volumetric magnetic resonance imaging (MRI). The putamen and caudate volumes were traced manually by a blinded rater, and the patient and control groups were compared using analysis of covariance adjusting for age, sex, intelligence quotient, and total brain volumes. RESULTS: MDD patients had significantly smaller right striatum (6.0% smaller) and right caudate volumes (7.4% smaller) compared to the healthy subjects. Left caudate volumes were inversely correlated with severity of depression in MDD subjects. Age was inversely correlated with left and right putamen volumes in MDD patients but not in the healthy subjects. CONCLUSIONS: These findings provide fresh evidence for abnormalities in the striatum of medication-na?ve pediatric MDD patients and suggest the possible involvement of the striatum in the pathophysiology of MDD.     

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis

European Archives of Psychiatry and Clinical Neuroscience - The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy...     

Larger putamen size in antipsychotic-naïve individuals with schizotypal personality disorder

ObjectiveTo (a) compare the size of the dorsal and ventral striatum (caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD.MethodsThe left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group × Region (caudate, putamen) × Slice (1–5: ventral, 2, 3, 4, dorsal) × Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain.ResultsPrimary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms.ConclusionsStriatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis.     

Anterior cingulate activation in antipsychotic-naïve first-episode schizophrenia

Objective: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. Method: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. Results: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. Conclusion: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication.     

The relationship of neuropsychological test performance with the PANSS in antipsychotic naïve, first-episode psychosis patients

The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative requires, among other things, the establishment of a reliable, valid, and consensus-derived method of assessing cognition. The derived battery will provide a standardized way to assess the effects of cognition-enhancing agents across clinical trials. To this end, the first of six consensus-oriented conferences was held April 2003. The goals were twofold: (a) To select which cognitive constructs to measure in a consensus battery, and (b) to select which criteria to use in evaluating tests for inclusion in the battery. Based on consultation with experts on the RAND Panel Method, 74 experts were invited to participate in a pre-meeting survey to provide information relevant to decisions on the cognitive battery. The survey included sections on reliability, validity, test administration, norms and interpretation of tests, cognitive domains and their integration, battery duration, and overall importance of test qualities. For selection of cognitive targets, the results showed that experts ranked executive functions, attention/vigilance, memory processes, and problem-solving ability highest. For test qualities, the experts ranked test-retest reliability, good coverage of key individual cognitive constructs, and comparable alternate forms highest. This article presents the results of the pre-conference survey that was the first step in the RAND process towards development of the NIMH-MATRICS consensus battery to assess cognition in schizophrenia.     

Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Prevalence and factors related to orthostatic syndromes in recently diagnosed,drug-naïve patients with Parkinson disease

Clinical Autonomic Research - The aim of this study was to explore the prevalence of and factors related to orthostatic syndromes in recently diagnosed drug-naïve patients with Parkinson...     

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia

Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.