Functioning In First-episode Psychosis Research Articles

Effects of modafinil on cognitive functions in first episode psychosis

Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia. We aimed to establish modafinil's role in the adjunctive treatment of cognitive impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease. Forty patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the effects of a single dose of 200mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention. Modafinil improved verbal working memory (d = 0.24, p = 0.04), spatial working memory errors (d = 0.30, p = 0.0004) and strategy use (d = 0.23, p = 0.03). It also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention, attentional set-shifting, learning or fluency. Modafinil selectively enhances working memory in first episode psychosis patients, which could have downstream effects on patients' social and occupational functioning.

Stress and Inflammation Reduce Brain-Derived Neurotrophic Factor Expression in First-Episode Psychosis

Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF.

FC07-01 - Cognitive functions in first episode psychosis

BackgroundCognitive impairment is recognized as an important feature of psychosis in its early stages and is a determinant of prognosis and management of these disorders.Aim of the studyTo test the cognitive functions in first psychotic episode in patients with disorders of schizophrenia, schizoaffective disorder, bipolar disorder and depression with psychotic disorder and to compare them to controls.Subjects and methodsThe study included 254 patients diagnosed according to Diagnostic and Statistical criteria of Mental disorders, 4th edition (91 schizophrenics, 21 with schizoaffective disorder, 107 with bipolar disorder and 31 with psychotic depression) and experiencing their first psychotic episode. Seventy healthy volunteers matched as regards age and sex with patients were used as controls. All are subjected to cognitive evaluation by Trail Making Test, part B, Wisconsin card sorting test 128, Benton Visual Retention Test and Wechsler Adult Intelligence Test.ResultsAll patients showed significant cognitive deterioration in all tests compared to control group. On comparing patients to each other, there was no significant difference between schizophrenics and patients with bipolar disorder, but both showed marked deterioration in comparison to depressive group.ConclusionCognitive impairments are present in early stages of psychosis and need careful assessment and management.

Apathy in first episode psychosis patients: One year follow up

Introduction This study describes how the negative subsyndrome of apathy develops over the first year in first episode psychosis (FEP) patients, with an emphasis on the prevalence of enduring apathy and the relationship between apathy, other symptoms and functioning. Methods Eighty four FEP patients were assessed both at baseline and after one year with the abridged clinical version of the Apathy Evaluation Scale (AES-C-Apathy). Other symptoms were assessed with the Positive and Negative syndrome scale (PANSS) and functioning with the split version of the Global Assessment of Functioning Scale (GAF-F). Results The mean level of AES-C-Apathy decreased from baseline to the one year follow up for the whole group of FEP patients. High levels of apathy at 1 year were best predicted by high levels of apathy at baseline, a long DUP and a diagnosis within the Schizophrenia spectrum. The presence of depression and level of medication only had a minor influence. AES-C-Apathy had a stronger association to GAF-F than other PANSS symptom areas. Twenty five (30%) FEP patients had high enduring levels of apathy. This group consisted of significantly more males, had a longer duration of untreated psychosis, a greater likelihood of a Schizophrenia spectrum diagnosis, fewer were in remission of positive symptoms and they had significantly poorer functioning at both baseline and follow up. Conclusion This study confirms that the negative subsyndrome of apathy is significantly related to poor functioning in FEP. Including negative symptoms and its subsyndromes in early detection strategies are warranted.

Apathy and Functioning in First-Episode Psychosis

This study aimed to determine which patient characteristics are associated with higher levels of apathy, to what degree first-episode psychosis patients are apathetic compared with a healthy control group, and to what degree apathy and other symptoms (including negative subsymptoms) influence functioning in first-episode psychosis. The Norwegian Thematically Organized Psychosis research study included 103 first-episode psychosis patients and a healthy control group of 62 persons. Apathy was assessed with the clinician-rated abridged version of the Apathy Evaluation Scale (AES-C-Apathy). Other clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The PANSS five-factor model was used in the subsequent analyses. Functioning was assessed with the split version of the Global Assessment of Functioning scale (GAF). More than 50% of first-episode psychosis patients were clinically apathetic compared with the healthy group. Of all clinical variables, only premorbid childhood social functioning, change in social functioning, and disorganized symptoms (PANSS disorganized component) had a significant association with AES-C-Apathy, explaining 18% of the variance. Multiple regression analysis revealed that of the five PANSS components, only PANSS positive made a significant independent contribution to the GAF-F score, as did the AES-C-Apathy score, explaining 37% of the variance. The same regression model indicated that among the PANSS negative symptoms, only flat affect made an independent significant contribution to functioning. Apathy is a prevalent symptom in first-episode psychosis and has a significant association with everyday functioning; the presence and consequences of apathy should thus be evaluated at the start of treatment.

Apathy and Functioning in First-Episode Psychosis

Apathy and Functioning in First-Episode Psychosis

Factors associated with functional psychosocial status in first‐episode psychosis

This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychological variables are most closely associated with functional status around the time of diagnosis of first-episode psychosis. This was with a view to determining factors that should be the focus of intervention in these early stages of illness. The Western Sydney First Episode Psychosis Project collected data on young persons (aged 13-25) with newly diagnosed psychosis (n=92). Psychosocial functional status was measured using the Role Functioning Scale (RFS). Multiple regression analyses were carried out to identify predictors of RFS score from a wide range of predictor variables. Psychiatric variables accounted for the most variance in RFS score. Positive and Negative Syndrome Scale (PANSS) Negative subscale and Young Mania Rating Scale score were found to be significant individual predictors, with variables from the other domains failing to contribute to the overall model. In separate models, demographic/premorbid and neuropsychological factors weakly related to functional status. Psychiatric factors were the main influence on psychosocial functioning in first-episode psychosis at baseline. Evidence suggests the relationships between symptoms, cognition and demographics with function might change over time, depending on the stage of illness being examined.

Apathy is associated with executive functioning in first episode psychosis

BackgroundThe underlying nature of negative symptoms in psychosis is poorly understood. Investigation of the relationship between the different negative subsymptoms and neurocognition is one approach to understand more of the underlying nature. Apathy, one of the subsymptoms, is also a common symptom in other brain disorders. Its association with neurocognition, in particular executive functioning, is well documented in other brain disorders, but only studied in one former study of chronic patients with schizophrenia. This study investigates the association between apathy and neurocognitive functioning in patients with first episode psychosis (FEP), with the hypothesis that apathy is more associated with tests representing executive function than tests representing other neurocognitive domains.MethodsSeventy-one FEP patients were assessed with an extensive neuropsychological test battery. Level of apathy was assessed with the abridged Apathy Evaluation Scale (AES-C-Apathy).ResultsAES-C-Apathy was only significantly associated with tests from the executive domain [Semantic fluency (r = .37, p < .01), Phonetic fluency (r = .25, p < .05)] and working memory [Letter Number Span (r = .26; p =< .05)]; the first two representing the initiation part of executive function. Confounding variables such as co-occuring depression, positive symptoms or use of antipsychotic medication did not significantly influence the results.ConclusionWe replicated in FEP patients the relationship between apathy and executive functioning reported in another study for chronic patients with schizophrenia. We also found apathy in FEP to have the same relationship to executive functioning, as assessed with the Verbal fluency tests, as that reported in patients with other brain disorders, pointing to a common underlying nature of this symptom across disorders.

Course of Cognitive Functioning in First-Episode Psychosis: A Comparison Between Schizophrenia and Non Schizophrenia Psychosis

AimsTo describe the course of cognitive functioning in first-episode psychosis and to determine possible differences in the degree and trajectory of cognitive deficits between schizophrenia and non-schizophrenia first-episode psychosis. MethodWe assessed attention, working memory, and executive functioning in 57 patients with first-episode psychosis both at baseline and at 1-year of follow-up. ResultsFor the overall group, significant reductions were found in the percentage of omission and commission errors for the sustained attention task (P<.001 and P=.001, respectively), in the total time to complete the Stroop-I task (P<.001), in the percentage of omission errors for the working memory task (P=.001), and in the percentage of perseverative errors for the Wisconsin card sorting test (WCST; P<.001), as well as a significant increase in the number of categories completed in the WCST (P<.001). The remaining cognitive variables analyzed remained stable (4 of the 10 variables tested). The pattern of change was similar for patients with schizophrenia (n=20) and nonschizophrenia (n=37) in the areas of attention of working memory. For executive functioning, the non-schizophrenia group showed a more beneficial pattern of change. No significant differences were detected in the cognitive performance among subgroups at baseline or at the 1-year follow-up. ConclusionsThe course of cognitive deficits in first-episode psychosis showed significant improvements over the 1-year period in the areas of attention, working memory, and executive functioning. Neuropsychological performance did not seem to be specific enough to distinguish between patients with schizophrenia and non-schizophrenia first-episode psychosis, at least during the first year.

P.3.b.002 Does COMT polymorphism influence cognitive function in first episode psychosis?

Three studies were conducted to evaluate the influence of environmental context and UCS preexposure intensity on the acquisition of a flavor aversion. In the first study, rats were exposed to two UCS-alone presentations at one of three dose levels of LiCl. The rats were given the two UCS preexposures in one of two contexts (familiar or novel). Following the UCS-alone treatment, all of the subjects received two pairings of sucrose and LiCl (1.25 meq) in the familiar context. Animals receiving UCS preexposures in the same context as used during conditioning consumed significantly more sucrose than did saline control animals. In contrast, the influence of prior UCS preexposure was not evident when UCS preexposure was experienced in a context different from that experienced during conditioning. In Experiment 2, all animal received UCS preexposure and conditioning in the novel room. Animals received either two or four preexposures at 0, 1.25, or 3.75 meq dose of LiCl. Two UCS preexposures at 3.75 meq dose produced a stronger UCS preexposure effect than did the 1.25 meq dose. Animals in Experiment 3 received two exposures to either 0-, 1.25-, or 3.75-meq LiCl in one of two contexts, followed by conditioning with the 1.25-meq LiCl dose in the same context as preexposure. Greater UCS interference occurred in animals preexposed to LiCl in the novel rather than familiar environment, with no specific dose effects in either context. These observations are discussed in terms of context blocking and generalization decrement models of the UCS preexposure effect.

Duration of untreated psychosis and neuropsychological function in first episode psychosis

Purpose We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. Method 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. Results Longer DUP was associated with impaired performance in verbal IQ ( p = 0.04), verbal learning ( p = 0.02), and verbal working memory ( p = 0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. Conclusions Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Premorbid adjustment and neurocognitive functioning in first episode psychosis

Background and aims:There is preliminary evidence that cognitive functioning is influenced by premorbid adjustment. The goal of this study was to examine to what extent premorbid adjustment patterns are related to cognitive functioning in a cohort of first-episode psychosis.Methods:Seventy-seven neuroleptic-naive patients with a first-episode of psychosis underwent clinical and neuropsychological assessments at baseline, 1 month and at 6 months of follow-up. Cognitive measurements included were: Verbal Fluency Test, Trail Making-B Test, Wechsler Memory Test, Reaction Time task, Wisconsin Card Sorting Test (WCST) perseverative errors. Patterns of premorbid functioning were categorised in two groups: ‘stable-good’ group and ‘poor and declining’ group, using the Cannon-Spoor Premorbid Adjustment Scale.Results:No significant associations were found between premorbid adjustment change scores and cognitive variables in the stable-good adjustment group. Patients with premorbid deterioration change score in premorbid adjustment between childhood and early adolescence was associated significantly with lower improvement at the follow-up in the Wechsler Memory Test (r=-0.511; p=0.009) and Reaction Time task (r=0.435; p=0.030). Moreover, change score in premorbid adjustment between early and late adolescence was significantly associated with lower improvement in perseverative errors (r=-0.455; p=0.022).Conclusions:Deterioration of premorbid adjustment was significantly associated with lower improvement of cognitive improvement at the 6 months follow-up in a first episode psychosis. This lower cognitive improvement varied with the timing of the deterioration process in premorbid adjustment. Early adolescence premorbid deterioration was associated with less improvement in attentional and memory tasks. And premorbid deterioration in the late adolescence was related to lower improvement on executive tests.

P.3.04 Does COMT polymorphism influence cognitive function in first episode psychosis?

P.3.04 Does COMT polymorphism influence cognitive function in first episode psychosis?

Distinct patterns of premorbid social functioning in first-episode psychosis: Relationship to initial presentation

Objective:To explore different longitudinal patterns of social functioning before onset of psychotic illness and how they relate to clinical presentation, substance use and acute treatment response.Methods:Inclusion criteria: Drug-naive first-episode psychosis, 18-50 yo, criteria for Schizophrenia or Other Psychotic Disorders (DSM-IV), excluding Psychotic Disorder due to a General Medical Condition and Substance-Induced Psychotic Disorder.Exclusion criteria:Mental Retardation, neurological disease, brain injury or drug dependence.Measures:Premorbid Adjustment Scale (PAS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS).Statistical analysis:Ward cluster analyses were carried out to differentiate three longitudinal patterns of social premorbid adjustment from childhood to late adolescence: stable good (N=75), stable bad (N=44) and deteriorating (N=35). Chi-square and ANOVA tests were used.Results:154 subjects (64.5% male, mean age 26.81, SD=6.98) participated in the study.At baseline the socially stable good group had more positive symptoms, SAPS 13.85 (3.99), than the stable bad group, SAPS 11.82 (3.93) (p=0.023).At six weeks post-treatment the socially deteriorating group had more negative symptoms, SANS 8 (4.89), than the stable good, SANS 3.85 (4.11), and the stable bad, SANS 5.23 (5.45) (p=0.000).The stable good group had the highest rates of substance use, followed by the deteriorating group.Conclusions:A good premorbid social life was related to higher substance use and more positive symptoms at presentation. A social deteriorating pattern was associated with more negative symptoms at baseline and six weeks post-treatment. These differences would argue for different pathogeneses of psychosis.

The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse

The aim was to determine the post-onset longitudinal course of cognitive functioning in first-episode psychoses and to examine how premorbid adjustment, duration of untreated psychosis (DUP), and clinical variables such as relapse are associated with that course. Consecutive patients with a DSM-IV diagnosis of non-organic psychosis coming to their first treatment in the health care areas under study were included. Ultimately, 207 patients were assessed neuropsychologically at baseline, 138 were reassessed one year later, and 111 two years later. Five dimensions were identified through principal component analysis of eight neuropsychological (NP) test results: Working Memory (WM), Executive Function (EF), Verbal Learning (VL), Impulsivity (Im), and Motor Speed (MS). No major changes were found in the level of neurocognitive functioning from baseline to the 1-year and 2-year follow-ups. Patients with good initial levels of premorbid academic functioning had consistently better scores on WM at all three time points. No association was found between DUP and the longitudinal course of neurocognitive function. Significant associations occurred between better WM and VL at 1 and 2 years and fewer relapses during the first year, but not the second. Most NP deficits are in place by onset of psychosis and are stable over two years. Milder WM deficits are associated with higher premorbid academic functioning. More severe deficits in WM and VL are associated with more relapses during the first year. It is unclear whether NP deficits cause relapse, relapse causes NP deficits, or both are manifestations of a third deteriorative process.

P.3.d.013 Correlation between acute atypical antipsychotic treatment and cognitive functioning in first episode psychosis

P.3.d.013 Correlation between acute atypical antipsychotic treatment and cognitive functioning in first episode psychosis

The course of cognitive functioning in first episode psychosis: Changes over time and impact on outcome

This three year longitudinal study examined the cognitive performance of 247 individuals who recently presented with a first episode of psychosis. Using a comprehensive battery of cognitive tests, we assessed cognition at baseline, 1 year and 2-year follow-ups. Assessments also included positive and negative symptoms, depression, social outcome and substance use. There were several significant improvements in cognition over the two-year period which were usually matched by improvements in a matched non-psychiatric control group. Regression analyses demonstrated that after controlling for symptoms cognitive impairment accounted for 4–6% of the variance in social functioning. Our results suggest that impaired cognition exists in the very early stages of a psychotic illness and that there is no decline over time. Secondly, our results suggest that, although related, poor social functioning deficits may be independent of cognitive impairment. Finally there are implications for improved methodology in the assessment of both cognitive and social functioning.

Patterns of premorbid functioning in first episode psychosis: relationship to 2‐year outcome

To determine how different patterns of premorbid functioning relate to outcome longitudinally. Premorbid adjustment was assessed in 194 first-episode of psychosis subjects. Positive and negative symptoms, depression, substance misuse and social and cognitive functioning were assessed over 2 years. Four patterns of premorbid adjustment: stable-good, stable-intermediate, poor-deteriorating and deteriorating were identified. Relative to the stable-good group, the deteriorating and poor-deteriorating groups had significantly more positive symptoms at 1-year follow-up but not at 2-year follow-up and significantly more negative symptoms and significantly poorer social functioning at both 1 and 2-years. Only verbal fluency and memory differentiated between the groups with the stable-good group having a superior performance. Those who demonstrated poor or deteriorating functioning prior to the onset of acute psychosis have a poorer outcome up to at least 2 years in terms of negative symptoms and social functioning.

The association between social anxiety and social functioning in first episode psychosis

The purpose of the study was to examine the relationship between social anxiety and social functioning in first episode psychosis, and to determine whether those with psychosis have any maladaptive or irrational beliefs regarding social situations. A sample of 60 first episode patients (41 males, 19 females) participated in the study. The presence of social phobia was determined using the Structured Clinical Interview for DSM-IV (SCID-I). Measures included The Social Phobia and Anxiety Inventory (SPAI), the Social Functioning Scale (SFS), the Quality of Life Scale (QLS) and the Social Interaction Self-Statement Test. Thirty-two percent of the sample met SCID-I criteria for social phobia and approximately 60% of participants were experiencing elevated levels of social anxiety according to the SPAI ( M=69.57, S.D.=27.42). Results were that negative symptoms and negative self-statements, but not social anxiety, were significant predictors of social functioning. This has implications for addressing these negative cognitions in early psychosis.

A goal-directed behaviour model of neurocognitive and behavioural functioning in first episode psychosis — A preliminary report of the first study

A goal-directed behaviour model of neurocognitive and behavioural functioning in first episode psychosis — A preliminary report of the first study