Neurocognitive functioning in subjects at risk for a first episode of psychosis compared with first- and multiple-episode schizophrenia

Evidence from neurobiological studies suggests that schizophrenia arises from an early abnormality in brain development and possibly further progressive developmental mechanisms. Despite a delay between the acquisition of neuropathology and the triggering of psychosis, neurobiological susceptibility is likely to be expressed subclinically by biobehavioral markers in the premorbid stage. The exploratory study aims at identifying potential neurocognitive risk factors and investigating the unfolding of the illness within a cross-sectional design by comparing neurocognitive profiles in 179 healthy controls, 38 clinically identified subjects in an early initial prodromal state (EIPS) for psychosis, 90 subjects in a late initial prodromal state (LIPS), 86 first-episode patients with schizophrenia, and 88 multiple-episode patients. Subjects at risk were substantially impaired in verbal executive and verbal memory functions. Compared to EIPS subjects, LIPS subjects demonstrated additional attentional deficits. Both EIPS and LIPS subjects were superior to first-episode patients who presented a generalized neuropsychological deficit profile, and to multiple-episode patients who showed evidence for further decline. Although results were influenced by general intellectual abilities and demographic and clinical characteristics, they could not account for total group differences. Results support a neurodevelopmental model of psychosis with further progressive mechanisms and are consistent with a primary involvement of left frontotemporal networks in the prodromal phase.     

Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes.     

Subjective quality of life in first episode schizophrenia spectrum disorders with comorbid depression

Previous studies have reported high prevalence rates of depressive symptoms or syndromes in subjects with first episode psychosis, but data are lacking on the quality of life (QOL) in these subjects. This cross-sectional study seeks to compare the subjective QOL of these individuals with and without a comorbid depressive syndrome at baseline. Using the Structured Clinical Interview to Diagnose DSM IV-Axis I Disorders, the Scale to Assess Unawareness of Mental Disorders (SUMD), Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAM-D), and the World Health Organization Quality of Life-Bref Scale (WHOQOL-BREF), we evaluated 66 consecutive subjects with first episode schizophrenia spectrum disorders (schizophrenia, schizoaffective and schizophreniform disorders) in our Early Psychosis Intervention Program. We found that subjects with a comorbid depressive syndrome had greater awareness of their mental illness, its social consequences and treatment efficacy, but poorer overall QOL, especially in the physical, psychological health, social relationships and environmental domains. The poorer QOL in subjects with a comorbid depressive syndrome may be explained by the greater degree of insight in these patients and their attributing their troubles to poor health, unsatisfactory social support and negative environment. Alternative explanations are also possible, providing possible foci for psychological support and intervention.     

Neuropsychological status of subjects at high risk for a first episode of psychosis

Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.     

Predictors of schizophrenia in patients with a first episode of psychosis

Early identification of schizophrenia in patients with a first episode of psychosis (FEP) may help to avoid inappropriate treatment and may enhance long-term outcome by addressing issues such as family network, treatment adherence and functional and symptomatic outcome. It was the aim of the study to determine baseline variables that significantly predicted a diagnosis of schizophrenia in patients with FEP. The sample consisted of 133 FEP patients hospitalized for at least 6 weeks, in whom a DSM-IV diagnosis was confirmed after 1 year follow-up. Patients were divided into two groups, those with a diagnosis of schizophrenia (Schizophrenia group, n = 63; 47.8%), and those with other psychosis, who were grouped under Non-Schizophrenic Psychosis (NSP, n = 70; 52.2%). Sociodemographic (marital status, educational level) and clinical variables were recorded for each patient. Substance use (alcohol, cannabis and cocaine) did not statistically differ between the two groups. Absence of characteristics defined as criteria for good prognosis, lack of ≥ 20% improvement in the total Positive and Negative Syndrome Scale score at 6 weeks, and a poor premorbid adjustment as determined by the Premorbid Adjustment Scale score significantly predicted the presence of schizophrenia. The regression model including these three variables achieved a predictive value of 76.3%, with a sensitivity of 74.6% and a specificity of 77.9%.     

Neurological soft signs and brain structural abnormalities in patients with first episode psychosis and healthy controls

ObjectivesTo assess and compare neurological soft signs (NSSs) and brain magnetic resonance imaging (MRI) findings between the patients with first episode psychosis and a group of healthy participants.MethodsThirty patients with first episode psychosis and thirty healthy participants were evaluated for psychiatric disorders using Structured Clinical Interview for DSM-IV, Axis I disorders (SCID-I). The assessment of NSSs and handedness was done using Neurological Evaluation Scale (NES) and Edinburgh Handedness Inventory (EHI), respectively. Moreover, a brain structural evaluation was done by using MRI.ResultsIn the patients with first episode psychosis, the total score of NES was significantly higher than in the healthy participants. The scores for the subgroups sequencing of motor acts (p < 0.01), motor coordination (p < 0.001) and sensory integration (p < 0.01) were higher for the patients in comparison with the healthy group. Several abnormal findings of MRI were significantly higher in the patients’ group as compared with the healthy group consisted of cortical atrophy, decrease in upper temporal cortex, and increase in the width of left Sylvian fissure volume.ConclusionNSSs were higher in the patients with first episode psychosis than in the healthy participants. NSSs and structural abnormalities in MRI are part of neurological deficit, leading to psychosis, and are not caused by the process of neurological deterioration due to psychosis itself. The current study is cross-sectional, so longitudinal data is required for elucidating if NSSs change during the course of illness.     

精神分裂症超高危人群及首次发病患者的认知功能研究

目的:探讨精神分裂症超高危人群及首次发病患者认知功能损害特点。方法:运用精神分裂症认知功能成套测验-共识版(MCCB)和Stroop色词测验对精神分裂症超高危者(超危组)、首次发病患者(首发组)及正常对照者(正常组)进行认知功能评定,每组各20例。结果:3组间连线测试和霍普金斯词语学习测验修订版(HVLT-R)成绩差异无统计学意义;符号编码、简易视觉记忆测验-修订版(BVMT-R)、持续操作测验(CPT)成绩各组间差异有统计学意义(P均0.05);超危组成绩介于首发组与正常组。结论:精神分裂症患者发病前已出现认知功能损害,并可能随疾病发作进一步加重。     

Health-related quality of life and psychiatric comorbidity in first episode psychosis

BACKGROUND: Quality of life (QOL) has been increasingly recognized as an important outcome measure in the care of patients with severe mental illnesses. This study seeks to evaluate the health-related QOL in patients with first episode psychosis and comparing those with psychiatric comorbidity to those without in an Early Psychosis Intervention Program. METHODS: Overall, 131 patients with first episode psychosis were evaluated on their principal Axis I diagnosis and any other comorbid diagnosis, severity of psychopathology, insight, social/occupational functioning, and QOL, respectively. RESULTS: Patients with psychiatric comorbidity scored lower on Positive and Negative Symptom Scale positive symptom subscale (z = -2.84, P <.01), had a greater awareness of their mental illness (z = -3.44, P <.001) and its social consequences (z = -3.24, P < 0.001), but lower ratings on the overall QOL (z = -3.06, P < 0.01) as well as in the individual domains (physical, psychological health, social relationships, environment, all P < .05) compared with patients without any psychiatric comorbidity. On multivariate analysis, being single and the presence of psychiatric comorbidity were associated with a poorer QOL in the various subdomains. CONCLUSIONS: The association of psychiatric comorbidity with poorer QOL warrants attention. The differences in the clinical correlates may provide potential targets for early identification and highlight needs that are significant to these patients with first episode psychosis and psychiatric comorbidity.     

Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis.     

Sensory gating in subjects at ultra high risk for developing a psychosis before and after a first psychotic episode

Objectives. To explore sensory gating deficits in subjects at Ultra High Risk (UHR) for psychosis before and after transition to a first psychotic episode. Methods. Sensory gating was assessed with the paired click paradigm in 61 UHR subjects, of whom 18 (30%) made a transition to psychosis (UHR + T) over a 3-year follow-up period and 28 matched healthy controls. Subjects were assessed at inclusion and again after approximately 18 months. P50, N100 (N1) and P200 (P2) sensory gating was established using the amplitude on the first (S1) and second (S2) click, the ratio- (S2/S1) and the difference score (S1-S2). Psychopathology was also assessed. Results. At baseline, UHR + T subjects presented smaller N1 difference scores compared to UHR + NT subjects and controls. The N1 difference score contributed modestly to the prediction of a first psychotic episode. Repeated measure analyses revealed smaller N1 and P2 S1 amplitudes, smaller P2 difference scores and larger P2 ratio's at follow-up compared to baseline in UHR + T subjects. Conclusion. The N1 difference score may be helpful in predicting a first psychosis. N1 and P2 sensory gating measures also showed alterations between the prodromal phase and the first psychosis, suggesting that these changes may relate to the onset of a frank psychotic episode.     

CSF sub-compartments in relation to plasma osmolality in healthy controls and in patients with first episode schizophrenia

Preliminary evidence suggests that plasma Na(+) level/osmolality may have effects on brain morphology; thus we investigated the link between plasma osmolality and ventricle size in healthy controls and patients with first episode schizophrenia. A total of 16 patients and 28 healthy controls were examined with magnetic resonance imaging (MRI) and gave blood samples. High-resolution 3D SPGR images were obtained on a 1.5 Tesla scanner. Scalp-edited MRI volumes were used for estimates of intracranial gray, white matter and CSF. Regional changes in CSF concentration and ventricular morphology were measured. The groups did not differ in plasma osmolality, but patients had higher plasma Na(+). There were no differences in ventricle size. Controlling for plasma osmolality did not change the results. A mixed model procedure indicated a significant group effect and a significant osmolality by group interaction in ventricle measures. Healthy control group showed a significant relationship between osmolality and ventricle measures; this relationship was absent in the patients. Significant correlations between osmolality and lateral ventricle surface deformations were observed along the superior horn of the lateral ventricles in the healthy controls. These results suggest that plasma osmolality is related to ventricle size in healthy volunteers and that this physiological link is impaired in patients with first episode schizophrenia.     

Neurocognitive performance in subjects at ultrahigh risk for schizophrenia: a comparison with first-episode schizophrenia

Objective

The aim of the present study was to explore the neurocognitive performance of patients at ultrahigh risk (UHR) compared with patients with first-episode (FE) schizophrenia and healthy control (HC) subjects.

Method

Twenty-seven subjects at UHR for schizophrenia, 25 patients in their FE of schizophrenia, and 33 HCs were included. All participants completed a neurocognitive battery, including tests of general intelligence, attention and working memory, executive function, and verbal and visual memory.

Results

Of the 3 groups, the FE subjects performed poorest at all neurocognitive tests, encompassing the broad range of impairments. The UHR subjects had a similar pattern of neuropsychological dysfunction but less severe than that of FE patients. The UHR subjects were particularly impaired on measures of attention and working memory, executive function, and verbal memory compared with the HCs.

Conclusion

These findings are consistent with the view that the neurocognitive impairments of schizophrenia are neurodevelopmental in nature and, although less severe, those impairments are mostly in place before the onset of the first frank psychotic episode. Neurocognitive impairments may play an important role in the pathogenesis of early psychosis and could help to clarify individuals at UHR for schizophrenia.