Rosa Ayesa-Arriola

White Matter Integrity and Cognitive Impairment in First-Episode Psychosis

OBJECTIVE Impaired cognitive function has been identified as a core feature of schizophrenia. However, a significant proportion of patients do not show any cognitive deficits. The aim of this study was to assess if there were differences in white matter integrity between patients with and without cognitive impairment. METHOD A diffusion tensor imaging study and neurocognitive assessment were conducted in 49 patients with first-episode psychosis and 41 healthy comparison subjects. Subjects were assessed using the Continuous Performance Test, the Grooved Pegboard Test, the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B. For each test, the patient sample was subdivided according to performance, with those scoring more than one standard deviation below the normative mean categorized as impaired. For each cognitive domain, white matter fractional anisotropy in deficit and nondeficit subgroups was compared using a voxel-based analysis. A nonparametric statistical method, controlling for multiple comparisons, was applied. RESULTS Impairment on the Trail Making Test Part B was associated with reduced fractional anisotropy in the right/left anterior thalamic radiation and inferior fronto-occipital fasciculus, forceps minor, and left superior and inferior longitudinal fasciculi. Patients exhibiting Grooved Pegboard Test impairment showed reduced fractional anisotropy in the forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal and corticopontine tracts. Impaired performance on the Rey Auditory Verbal Learning Test and Continuous Performance Test was not associated with significant differences in fractional anisotropy. CONCLUSION Deficits in executive and motor functioning in patients with first-episode psychosis are associated with reductions in white matter integrity in the major fasciculi that connect the frontal and temporal cortices as well as in pathways connecting cortical and subcortical regions. Their presence at the onset of illness, in minimally medicated patients, indicates that these findings are not attributable to effects of chronic illness or its treatment.

Cannabis use and cognitive functioning in first-episode schizophrenia patients

Cannabis is one of the most widely used illicit drugs in the world. In healthy individuals cannabis is associated with cognitive impairments. Research into the effect of cannabis use in schizophrenia has yielded contradictory findings. Our aim has been to explore the correlates of cannabis use in cognitive and psychopathological features, both cross-sectional and longitudinally, in early phases of schizophrenia. 104 patients with a first episode of non-affective psychosis and 37 healthy controls were studied. Patients were classified according to their use of cannabis prior to the onset of the illness (47 users vs. 57 non-users). They were cross-sectionally and longitudinally studied and compared on clinical and cognitive variables and also on their level of premorbid adjustment. Cannabis user patients had better attention and executive functions than non-cannabis user patients at baseline and after 1 year of treatment. Both groups showed similar improvement in their cognitive functioning during the 1-year follow-up period. We also found that users had a better social premorbid adjustment, particularly during the early periods of life. The amount of cannabis consumed and the length of time of consumption did not significantly relate to cognitive performance. The use of cannabis does not seem to be associated with a negative effect on cognition in a representative sample of first-episode schizophrenia patients. Cannabis user patients appear to comprise a subgroup of patients with a better premorbid adjustment and premorbid frontal cognitive functions.

The relevance of cognitive, clinical and premorbid variables in predicting functional outcome for individuals with first-episode psychosis: A 3 year longitudinal study

Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3 year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1 year and 77% at 3 year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness.

Homocysteine and cognition in first-episode psychosis patients

In the last years, there has been growing evidence linking elevated homocysteine levels with cognitive dysfunction in several neurological and neuropsychiatric diseases. The aim of the present study was to investigate the potential relationship between elevated homocysteine levels and cognitive deficits in first-episode psychosis patients. Plasma levels and cognitive performance of 139 patients and 99 healthy volunteers were compared. Patients were classified as elevated homocysteine (>90 percentile for controls) and normal and compared on 22 cognitive outcome measures grouped into cognitive domains known to be impaired in schizophrenia. Patients had a statistically significant increase in plasmatic homocysteine levels. In addition, they presented with significantly increased cognitive deficits. However, no relationship between homocysteine levels and cognitive impairment was detected. These results suggest the need for further studies to clarify the role of homocysteine in the etiology and prognosis of psychosis.

Course of cognitive deficits in first episode of non-affective psychosis: a 3-year follow-up study.

Cognitive dysfunctions are critical determinants of the quality of life and functionality in schizophrenia. Whether the cognitive deficits present at an early stage, are static or change across ones lifespan is still under debate. This study aims to investigate the long-term (3 years) course of cognitive deficits in a large and representative cohort of first episode schizophrenia spectrum patients (N=155),and evaluate their influence on disability. In addition, a healthy control sample (N=43) was also studied for comparison. This study evaluates the performance of patients and controls in a battery of cognitive assessments using baseline, 1-year and 3-year follow-up designs. The results show that, although cognitively outperformed by the controls at any time, the cognitive performance of the patients improved similar to the controls in all cognitive functions except verbal and visual memory. Even though the course of cognitive performance across the sample as a whole was stable, the subgroup of patients who experienced a cognitive decline had worse functionality and lesser amelioration of negative symptoms. Overall, there is no significant deterioration in the cognitive function in a group of first episode schizophrenia spectrum disorder patients, with the possible exception of tasks that were associated with episodic memory. However, patients whose cognitive performance demonstrated a declining trend may present with a poorer progression in terms of clinical and disability variables.

Insight dimensions in first-episode psychosis patients: clinical, cognitive, pre-morbid and socio-demographic correlates

Aim: To investigate pre‐morbid, socio‐demographic, clinical and cognitive variables as predictors of insight in a large and representative sample of first‐episode psychosis patients.

Prediction of acute clinical response following a first episode of non affective psychosis: Results of a cohort of 375 patients from the Spanish PAFIP study

OBJECTIVE Predicting response to antipsychotic treatment might optimize treatment strategies in early phases of schizophrenia. We aimed to investigate sociodemographic, premorbid and clinical predictors of response to antipsychotic treatment after a first episode of non-affective psychosis. METHOD 375 (216 males) patients with a diagnosis of non affective psychosis entered the study. The main outcome measure was clinical response at 6 weeks and variables at baseline were evaluated as predictors of response. ANOVA for continuous and chi-square for categorical data were used to compare responders and non-responders. Multivariate logistic regression was used to establish a prediction model. RESULTS 53.3% of study subjects responded to antipsychotic treatment. The following variables were associated with an unfavorable response: 1.--lower severity of symptoms at baseline; 2.--diagnosis of schizophrenia; 3.--longer DUI and DUP; 4.--poorer premorbid adjustment during adolescence and adulthood; 5.--family history of psychosis, and 6.--hospitalization. Patients with a family history of psychosis, longer DUP, poor premorbid functioning and lower severity of psychotic symptoms at intake have a reduced likelihood of responding to antipsychotic treatment. CONCLUSION Helping clinicians to identify those first episode patients with a lower probability of having a favorable clinical response is meant as a first step to achieve a successful initial treatment.

No sex differences in neuropsychological performance in first episode psychosis patients.

OBJECTIVE The purpose of this study was to verify whether male patients with psychosis have greater neurocognitive impairment than female patients at illness onset. METHOD Participants with a first episode of psychosis (74 women/86 men) and healthy controls (62 women/97 men) were assessed with an extensive neuropsychological test battery. RESULTS Women in the clinical group were older at illness onset and had achieved higher formal education than men. This trend was the same for the control group. The patient group presented with lower premorbid IQ compared to healthy controls, and performed below for most neuropsychological tests. Women scored higher than men on a test of verbal memory, whereas men scored higher than women on a test of reaction time, visual memory, and a planning task. There were no group-by-sex interactions for any of the neuropsychological tests. CONCLUSION The present study shows that at the onset of psychosis there are no differences between males and females in neuropsychological performance. The differential pattern of cognitive performance observed is similar to that in healthy males and females. Furthermore, females with a late onset of psychosis may represent a subgroup with specific visuospatial and problem solving impairments. SIGNIFICANT OUTCOMES LIMITATIONS

Effect of antipsychotic drugs on cortical thickness. A randomized controlled one-year follow-up study of haloperidol, risperidone and olanzapine

BACKGROUND Imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time. The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis. We aimed to investigate the effects of low doses of haloperidol, risperidone and olanzapine on cortical thickness. METHOD We investigated the effects of risperidone (N=16), olanzapine (N=18) and low doses of haloperidol (N=18) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients. The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed. A group of 45 healthy volunteers was also longitudinally evaluated. Magnetic resonance imaging brain scans (1.5T) were obtained and images were analyzed by using BRAINS2. RESULTS There were no significant effects of time (F(1,47)<1.66; P>0.204), treatment group (F(2,47)<1.47; P>0.242) or group-by-time interaction (F(2,47)<1.82; P>0.174) for any of the cortical thickness variables. When the group of healthy controls was included in the analyses, it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level (F(3,81)=2.686; P=0.052). After the Bonferroni adjustment for multiple comparisons, there were no significant associations between changes in cortical thickness and clinical and cognitive outcome. CONCLUSIONS Low doses of haloperidol, risperidone, and olanzapine seem to equally affect gray matter cortical thickness, overall and lobes, at the medium-term (1 year). The clinical effectiveness of treatments was not significantly related to changes in cortical thickness.

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

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