Patient outcomes in schizophrenia II: the impact of cognition.

BACKGROUND: Cognitive dysfunction is increasingly considered to be the strongest clinical predictor of poor long-term outcome in schizophrenia. Associations have been found between the severity of cognitive deficits and social dysfunction, impairments in independent living, occupational limitations, and disturbances in quality of life (QOL). METHODS: In this cross-sectional study, the relationships of cognitive deficits and treatment outcomes in terms of QOL, needs, and psychosocial functioning were examined in 60 outpatients with schizophrenia who had a duration of illness over 2 years and had been treated with either clozapine or olanzapine for at least 6 months. RESULTS: The present study suggests that cognitive functioning might be a predictor of work functioning/independent living outcome in stabilized patients with schizophrenia: deficits of visual memory and working memory were negatively associated with occupational functioning, and older patients lived independently and/or in a stable partnership more often. The patients' assessments of QOL and needs for care did not show any significant associations with cognitive functioning. DISCUSSION: These findings suggest that cognitive functioning is a key determinant of work functioning/independent living for stable outpatients with schizophrenia.     

Correlates of subjective and functional outcomes in outpatient clinic attendees with schizophrenia and schizoaffective disorder

Outcome in schizophrenia is multidimensional and, thus, consists of clinical,humanitarian, rehabilitative and cost domains. Accordingly, recovery is conceptualized as the ability to function in the community, socially and vocationally, as well as being relatively free of disease–related psychopathology. The present cross–sectional study examined the relationship of premorbid functioning, psychopathology, insight, attitudes toward medication and side–effects, as well as sociodemographic factors with treatment outcomes in terms of quality of life (QOL) and psychosocial functioning among 60 regular attendees of a specialized schizophrenia outpatient clinic. Both insight into the illness as well as attitudes toward treatment indicated satisfactory compliance. Premorbid school and social functioning were positively correlated with actual employment status, and premorbid social functioning was further positively correlated with QOL and global functioning. Attitudes toward treatment were positively associated with global QOL, and with the patients' living situation. Both positive and negative symptoms as well as asthenia were negatively associated with QOL, while cognitive symptoms negatively influenced occupational functioning. Older patients lived independently and/or in a partnership more often, but had a lesser likelihood of competitive employment. Our observations suggest that subjective and functional outcomes in highly compliant patients are mainly predicted by psychopathological symptoms and unchangeable sociodemographic variables.     

Neurocognitive,clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia

Quality of life (QOL) impairment is evident in patients with schizophrenia and is increasingly recognised as an important evaluation criterion of treatment outcome. Hence, this study aimed to identify the neurocognitive, clinical and functional parameters associated with subjective QOL in patients with schizophrenia within an Asian context, and specifically in an outpatient setting. This study was conducted on 83 outpatients with DSM-IV diagnosis of schizophrenia, and 47 age- and gender-matched healthy controls. All participants were administered with the World Health Organisation Quality of Life Assessment-Brief Form (WHOQOL-BREF) and Brief Assessment of Cognition in Schizophrenia (BACS), to measure quality of life and cognitive function respectively. Patients were also assessed for severity of psychopathology, as well as level of psychosocial functioning, using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) rating scales respectively. Specific psychopathology (greater severity of PANSS negative symptoms, general psychopathology subscale scores), cognitive deficits (working and verbal memories), and lower GAF scores were correlated with poorer QOL in patients. Multivariate analyses revealed that younger age, being single and lower level of psychosocial functioning were associated with poorer QOL but level of psychosocial functioning did not appear to mediate the effects of symptoms and neurocognitive deficits on QOL. Overall, this study highlighted the need for clinicians to pay more attention to these clinical, neurocognitive and functional parameters and their integrative relationships with QOL in order to optimise the treatment outcomes of patients with schizophrenia.     

Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects

BACKGROUND: Quality of life (QOL) is now seen as a key outcome variable in schizophrenia. Factors deemed relevant in this context include severity of symptoms, antipsychotic-induced side effects, sociodemographic variables, and patients' subjective response to medication. METHOD: In the current cross-sectional study, 80 patients with a schizophrenic disorder according to ICD-10 criteria who had a duration of illness over 1 year and whose discharge from an inpatient unit had been at least 6 weeks earlier were investigated. Apart from the registration of demographic data, various rating scales were used: the Positive and Negative Syndrome Scale (PANSS), the St. Hans Rating Scale for Extrapy-ramidal Syndromes, the UKU Side Effect Rating Scale, the Drug Attitude Inventory, and the Lancashire Quality of Life Profile. RESULTS: More than half of all patients (47/80) indicated that they were satisfied with their life in general. The specific areas of subjective dissatisfaction that were most commonly noted in the present sample concerned partnership and mental health. The depression/anxiety component of the PANSS, parkinsonism, and a negative attitude toward antipsychotic medication negatively influenced the patients' QOL, while cognitive symptoms and employment status correlated with higher QOL. CONCLUSION: Our results highlight the importance of recognizing the complex nature of QOL in schizophrenia patients. They suggest that special attention should be paid to patients who experience anxiety and depressive symptoms or parkinsonism, to those who are unemployed, and to those with negative feelings and attitudes toward antipsychotics.     

Subjective and objective quality of life in schizophrenia

OBJECTIVE: Quality of life (QOL) is considered an important outcome in the treatment of schizophrenia, but the determinants of QOL are poorly understood in this population. Furthermore, previous studies have relied on combined measures of subjective QOL (usually defined as life satisfaction) and objective QOL (usually defined as participation in activities and relationships). We examined separately the clinical, functional, and cognitive predictors of subjective and objective QOL in outpatients with schizophrenia. We hypothesized that better subjective QOL would be associated with less severe negative and depressive symptoms, better objective QOL, and greater everyday functioning capacity, and that better objective QOL would be associated with less severe negative and depressive symptoms, better cognitive performance, and greater functional capacity. METHOD: Participants included 88 outpatients with schizophrenia or schizoaffective disorder who completed a comprehensive series of assessments, including measures of positive, negative, and depressive symptoms; performance-based functional skills; a neuropsychological battery; and an interview measure of subjective and objective QOL. RESULTS: In the context of multiple predictor variables, more severe depressive symptoms and better neuropsychological functioning were independent predictors of worse subjective QOL. More severe negative symptoms predicted worse objective QOL. Functional capacity variables were not associated with subjective or objective QOL. CONCLUSION: Treatments to improve QOL in schizophrenia should focus on negative symptoms and depressive symptoms.     

Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia

Poor social and vocational outcomes have long been observed in schizophrenia. Two of the most consistent predictors are negative symptoms and cognitive impairment. We investigate the hypothesis that cognitive content--defeatist beliefs regarding performance--provides a link between cognitive impairment, negative symptoms, and poor functioning in schizophrenia. A total of 77 individuals (55 patients diagnosed with schizophrenia or schizoaffective disorder and 22 healthy controls) participated in a cross-sectional study of psychopathology. Tests of memory, abstraction, attention, and processing speed, as well as current psychopathology, functioning, and endorsement of defeatist beliefs, were employed. Greater neurocognitive impairment was associated with elevated defeatist belief endorsement, higher negative symptom levels, and worse social and vocational functioning. Notably, statistical modeling indicated that defeatist belief endorsements were mediators in the relationship between cognitive impairment and both negative symptoms and functioning. These effects were independent of depression and positive symptom levels. The results add to the emerging biopsychosocial understanding of negative symptoms and introduce defeatist beliefs as a new psychotherapeutic target.     

Facial emotion recognition and its relationship to symptomatic,subjective, and functional outcomes in outpatients with chronic schizophrenia

Outcome in schizophrenia is multidimensional and consists of clinical and psychosocial domains. Difficulties in affect recognition are a hallmark of schizophrenia, but there is little research investigating the consequences of this deficit on patients’ psychosocial status. This cross-sectional study examined the relationship of facial affect recognition and treatment outcomes in terms of psychopathology, quality of life (QOL), and psychosocial functioning.We investigated 40 regular attendees of a specialized schizophrenia outpatient clinic who had been stable both from a symptomatic and a medication perspective for a minimum of 6 months and 40 healthy volunteers who were chosen to match patients in age, sex, and education. Affect recognition was positively associated with patients’ level of education and negatively with increasing age. Deficits in this area corresponded to the severity of negative and affective symptoms as well as to poor work and global functioning. These findings suggest that affect recognition is an important aspect of psychosocial functioning in stable outpatients with schizophrenia.     

Effectiveness, safety, and tolerability of ziprasidone for treating schizophrenia patients undergoing usual care: a 12-month, open-label, flexible-dose, naturalistic observational trial

OBJECTIVE: This is a first report from a long-term study aimed to evaluate efficacy, safety, tolerability, cognitive functioning, and quality of life outcomes during ziprasidone treatment of chronic schizophrenia patients in the "real-world". METHOD: Seventy clinically unstable schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40-160 mg/day), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI-S) scale, the Global Assessment of Functioning Scale (GAF) scores, treatment-emergent adverse events, body weight, and drug attitude. RESULTS: Thirty-two patients fully completed the study protocol. A discontinuation of treatment for any cause occurred in 54.3% of patients; the mean time until discontinuation was 4.4 +/- 2.7 months. A discontinuation due to lack of clinical efficacy was more predominantly linked to patient perception (25.7%) than to physicians' conclusions alone (8.6%), adverse events (11.4%), and other reasons (8.6%). After controlling daily dose of ziprasidone, concomitant medications and sex, ANCOVA revealed improvement in PANSS factors, and global functioning among patients who had completed the study. Improvement in PANSS and GAF dimensions was evident at a 6-month visit, and it continued until the endpoint. When a cutoff of 20% improvement of PANSS total scores was used, the response rate among completers was 43.8%. Most common side effects were: fatigue, sleep disturbances, and headache. Ziprasidone did not appear to be linked to weight gain. CONCLUSION: This study suggests that ziprasidone may be beneficial for long-term treatment of schizophrenia patients in terms of severity of symptoms, and general functioning. Ziprasidone is well tolerated during the long-term treatment of chronic schizophrenia patients undergoing usual care.     

Improvements in spontaneity and social functioning in patients with schizophrenia after cognitive training

Cognitive rehabilitation approaches are in the spotlight as a novel strategy for promoting social participation in patients with schizophrenia, as the connection between cognitive deficits and functional outcomes in schizophrenia has been consistently demonstrated over the last decade. Divergent thinking is typically applied when someone is confronted with questions that do not have a single fixed answer. We identified divergent thinking deficits in patients with schizophrenia using qualitative measures involving idea and design fluency tests, and found that the impairment in generating high-quality responses on divergent thinking tasks was an important determinant of poor community functioning among patients. Based on our findings, we suggested that divergent thinking was an important neurocognitive skill that deserves consideration as a potential target for intervention, and developed a training program specifically for divergent thinking deficits in patients with schizophrenia. We evaluated the effects of this program on measures of divergent thinking (e.g., fluency measures), negative symptoms, and social functioning. After the training program, participants in the divergent thinking program had significantly greater improvements on measures of idea fluency, negative symptoms, and interpersonal relations than the participants in the control program. These results suggest that interventions for divergent thinking in patients with schizophrenia may lead to improvements in patients' social functioning. In recent years, intrinsic motivation has become a focus of attention as a critical mechanism for explaining the relationship between neurocognition and psychosocial functioning in patients with schizophrenia. Divergent thinking is thought to be relevant to spontaneity and intrinsic motivation. The training program for divergent thinking deficits may have achieved its effects on negative symptoms and social functioning through an improvement in spontaneity and intrinsic motivation. The potential of the cognitive training program to enhance patients' quality of life is discussed.     

Predictors of subjective and objective quality of life in outpatients with schizophrenia

Aim: In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease‐specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL. Methods: Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively. Results: Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL. Conclusion: Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL.     

Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment

OBJECTIVES: This study examined the relationships of measures of cognitive functioning and psychiatric symptoms with work outcomes and use of vocational services for clients with schizophrenia in a supported employment program. METHODS: Thirty clients who were newly enrolled in a supported employment program were evaluated with cognitive and symptom measures at program entry and two years later. The clients' amounts of competitive work, wages earned, on-job support, and contact with employment specialists during the two-year follow-up period were documented. RESULTS: Predictors of clients' work outcomes included previous work history, amount of government entitlement income received, severity of negative symptoms, involvement in sheltered work activity at baseline, and level of cognitive functioning, including scores on measures of executive functioning and verbal learning and memory. The amounts of on-job support and contact with employment specialists were predicted by the cognitive domains of executive functioning, verbal learning, attention, and psychomotor speed as well as by the severity of psychotic symptoms. CONCLUSIONS: Clients with schizophrenia who have higher levels of cognitive impairment may require greater amounts of vocational support than those with lower levels of impairment. A variety of rehabilitation strategies may be required to improve vocational outcomes and reduce the amount of supported employment services needed by clients with schizophrenia.     

Community dysfunction in schizophrenia: rate-limiting factors

The purpose of the present study was to investigate the impact of cognitive functioning, psychopathology, and severity of extrapyramidal side effects on community outcome in a group of Greek outpatients with schizophrenia. Participants were 40 outpatients with schizophrenia (25 men). Social adjustment was assessed with the Quality of Life Scale (QLS). Severity of symptoms of schizophrenia was measured with the Positive and Negative Syndrome Scale (PANNS), and extrapyramidal symptoms with the Extrapyramidal Symptom Rating Scale (ESRS). Finally, a battery of neuropsychological tests was administered in order to assess the following cognitive domains: executive functioning/set shifting, executive functioning/inhibition, fluency, verbal memory, visual memory, working memory, attention, visuospatial ability, and psychomotor speed/visual scanning. Total scores on the QLS were significantly correlated with negative symptoms, parkinsonism, and performance on the fluency tasks. Interpersonal relations subscale was significantly related with negative symptoms and fluency. No significant relationship was found between the Instrumental Role Functioning subscale and the PANSS, ESRS, or any cognitive domain. Scores on the Intrapsychic Foundation subscale were significantly correlated with negative symptoms and fluency. Finally, scores on the Common Objects and Activities subscale were significantly related with severity of negative symptoms, parkinsonism and visual memory. Our findings suggest that severity of negative symptoms, cognitive dysfunction, especially performance on fluency tasks and visual memory, as well as parkinsonism, are important determinants of functional outcome in schizophrenia.     

Humor appreciation deficit in schizophrenia: the relevance of basic neurocognitive functioning

The purpose in undertaking the present study was to investigate humor appreciation in patients with schizophrenia. Moreover, we sought to explore the potential relationship of humor appreciation with measures of psychopathology and cognitive functioning among the patients. Thirty-six patients with schizophrenia were compared with 31 normal controls matched for age, sex, and education on a computerized test comprising captionless cartoons: Penn's Humor Appreciation Test (PHAT). The patients were also evaluated on the symptom dimensions derived from the Positive and Negative Symptom Scale (positive symptoms, negative symptoms, cognitive symptoms, depression, and excitement), as well as a battery of neuropsychological tests measuring executive functions, attention, working memory, verbal and visual memory, visuospatial ability, and psychomotor speed. Patients with schizophrenia had significantly lower scores on the PHAT than normal controls. The patients' performance on the PHAT correlated with scores on Penn's Continuous Performance Test, the Stroop Color-Word Test, and the phonological subscale of the Greek Verbal Fluency Test. Our findings indicated impaired humor appreciation among patients with schizophrenia. The relationship found between the appreciation of captionless cartoons involved an incongruous detail and performance on a broad neuropsychological battery suggested that the deficit in humor appreciation in schizophrenia could be attributed to impairment in more basic neurocognitive domains, namely, selective and sustained attention as well as phonological word fluency.     

A meta-analysis of cognitive remediation in schizophrenia

OBJECTIVE: This study evaluated the effects of cognitive remediation for improving cognitive performance, symptoms, and psychosocial functioning in schizophrenia. METHOD: A meta-analysis was conducted of 26 randomized, controlled trials of cognitive remediation in schizophrenia including 1,151 patients. RESULTS: Cognitive remediation was associated with significant improvements across all three outcomes, with a medium effect size for cognitive performance (0.41), a slightly lower effect size for psychosocial functioning (0.36), and a small effect size for symptoms (0.28). The effects of cognitive remediation on psychosocial functioning were significantly stronger in studies that provided adjunctive psychiatric rehabilitation than in those that provided cognitive remediation alone. CONCLUSIONS: Cognitive remediation produces moderate improvements in cognitive performance and, when combined with psychiatric rehabilitation, also improves functional outcomes.     

Correlates of substance misuse in patients with first-episode schizophrenia and schizoaffective disorder.

OBJECTIVE: To identify factors associated with substance misuse in first-episode patients with schizophrenia or schizoaffective disorder. METHOD: Twenty-seven patients with a past or current history of substance misuse were compared with 91 patients with no history of misuse on demographic and psychopathological measures before being treated for their first episode of psychosis, and on cognitive measures after 6 months of treatment. RESULTS: There were no statistically significant differences between groups for sex, schizophrenia subtype, marital status, education, family history of schizophrenia, course of illness, age of onset, baseline symptoms, time to treatment response, medication side effects, attention span, memory and executive functioning. However, dual diagnosis patients were found to have a higher parental social class, better premorbid cognitive functioning, higher IQ and better language skills. CONCLUSION: First-episode patients with a history of substance misuse have higher intellectual functioning, which may be associated with higher premorbid socioeconomic status and cognitive functioning.     

Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine

BACKGROUND: Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure. OBJECTIVES: The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia. METHODS: In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI). RESULTS: Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life. CONCLUSIONS: Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.     

A comparative study on quality of life of patients of schizophrenia with and without depression

Depression in schizophrenia has been recognized as one of the important factors influencing the Quality of Life (QOL). For this study 60 patients with a clinical diagnosis of schizophrenia as per ICD-10 (DCR version) were divided into two groups (with and without depression) on the basis of their score on Calgary Depression Rating Scale for Schizophrenia (CDSS). Thereafter, all patients were assessed on Positive and Negative Syndrome Scale for Schizophrenia (PANSS) for psychopathology, on Lehman Quality of Life Interview (QOLI)-brief version for QOL, on World Health Organization Disability Assessment Schedule-II (WHODAS-II) for disability, on UKU Side Effect Rating Scale for side effects of drugs and on Social Support Questionnaire (SSQ) for perceived social support. The two (depressed and non-depressed schizophrenia) groups differed significantly on symptoms of general psychopathology of PANSS and disability as per WHODAS-II, with the depressed group scoring higher. In the total sample, positive symptoms and the symptoms of general psychopathology of PANSS had a strong negative correlation with all three (subjective, objective and combined) domains of QOL, whereas, disability and medication side effects had a negative correlation with subjective and combined domains of QOL. CDSS total score did not significantly correlate with QOL. General psychopathology symptoms of PANSS emerged as the sole significant predictor of subjective and combined QOL, while positive symptoms of PANSS emerged as the sole predictor of objective QOL. Hence, it can be concluded that general psychopathology on PANSS had significant effect whereas depression as rated on CDSS had no significant effect on QOL in patients with schizophrenia. Treatments to improve QOL in schizophrenia should focus on symptoms of general psychopathology of PANSS.     

Old patients suffering from long-standing schizophrenia: clinical aspects

Although some patients suffering from schizophrenia experience an age-related amelioration, a great number of people who are entering old age suffer from long-standing schizophrenia. These patients show specific psychiatric and somatic problems that must be taken into account. Firstly, some display high levels of all schizophrenic symptoms, while others experience changes in the symptom profile with aging, i.e. a reduction in positive symptoms and an increase in negative ones. Secondly, the occurrence of significant depressive symptoms among elderly patients with schizophrenia is well recognized. Thirdly, in recent years, studies have begun to shed more light on the trajectories of cognitive impairment of these patients in old age. Lastly, aged persons with schizophrenia often have side effects due to long-term antipsychotic medications and medical co-morbidity, more untreated somatic disorders (diabetes, cardiovascular diseases) and higher mortality rates. These may be the result of both lifestyle factors and lack of adequate medical care. Levels of adaptive functioning and quality of life are closely associated with clinical and social factors. Thus, we must consider all these different aspects in order to effectively manage the therapeutic and service needs of these patients.     

Outcomes in schizophrenia outpatients treated with amisulpride or olanzapine

INTRODUCTION: We compared stable patients with schizophrenia who were treated with either amisulpride or olanzapine in terms of symptomatic outcome, neurocognitive functioning, functionality, and subjective outcome. METHODS: Sixty outpatients with chronic schizophrenia who had been treated with either amisulpride or olanzapine for at least six months were investigated. RESULTS: The scores of positive, negative, and cognitive symptoms did not differ between the two groups, but patients treated with olanzapine had significantly lower scores on the excitement and depression/anxiety components of the PANSS. With regard to cognitive variables, patients treated with amisulpride showed significantly lower values regarding verbal fluency and significantly better verbal memory than patients treated with olanzapine. Both treatment groups were comparable with respect to functional and subjective outcome variables. DISCUSSION: These observations add to the evidence that continuous treatment with different second-generation antipsychotics with relatively few side effects leads to comparable outcomes in patients with schizophrenia.