Cognitive dysfunction in first-episode schizophrenia and its correlation with negative symptoms and insight.

BACKGROUND: Cognitive dysfunction in schizophrenia is a well-known feature and can adversely affect the patient participation in treatment and rehabilitation. Studies have shown its relationship to the severity of negative symptoms and level of insight also. Not many Indian studies are available on this in first-episode schizophrenia, and hence, this study was undertaken.
MATERIALS AND METHODS: Eight-five cases of first-episode schizophrenia fulfilling inclusion criteria were included in the study after ethical clearance, informed consent, and stabilization of acute symptoms. All were assessed using psychosocial pro forma, Addenbrooke's Cognitive Examination-III Scale, positive and negative syndrome scale, and schedule for the assessment of insight. Data analysis was done using Statistical Package for Social Sciences Version 20:0.
RESULTS: Cognitive dysfunction was seen in 40% of patients. Maximum dysfunction was in the memory domain followed by fluency domain and language domain was relatively well preserved. A significant negative correlation was observed between cognitive function and negative symptoms, but a significant positive correlation was seen with insight.
CONCLUSION: Cognitive dysfunction is present in a significant proportion of schizophrenia in the first episode itself. Early assessment will facilitate appropriate interventions directed at insight and cognitive rehabilitation. Copyright:

Impairments in cognitive functions are considered to be a “core feature” of schizophrenia.[1] They often affect a broad range of cognitive domains with severity ranging from mild to severe. Cognitive impairments appear to be present across the lifespan of patients, with evidence of detectable cognitive deficits before the onset of any symptoms, during prodromal phase, at the time of first psychotic episode, and through the course of schizophrenia.[2] An individual with cognitive impairment often experiences problems in his day-to-day functioning such as paying attention to a task, processing information quickly, remembering and recalling required information, responding to information promptly, thinking critically, and solving problems. These impairments often affect his/her ability to obtain and maintain successful employment, to be effective in functioning in community and more importantly in participating in treatment and rehabilitation activities.[3]

A meta-analysis by Schaefer et al. which analyzed data from 100 studies involving 9048 patients with chizophrenia and 8814 controls revealed substantial, generalized cognitive impairment in patients with schizophrenia with moderate-to-severe impairments relative to controls across all neuropsychological measures studied (effect size −1.03), and somewhat larger cognitive differences in the domains of processing speed (effect size −1.25) and episodic memory (effect size −1.23).[4]

Talreja et al., in 2013, assessed patients with schizophrenia by using Addenbrooke's Cognitive Examination-Revised (ACE-R) scale.[5] It showed that 70% of patients had cognitive dysfunction in the domains of attention, language, memory, concentration, and executive function. Patients with a duration of illness of more than 2 years and residing in urban habitat showed more cognitive dysfunction. Impairment in the domains of language and memory was associated with male gender.

Among patients with schizophrenia, negative symptoms and cognitive dysfunction have been reported to be correlated in cross-sectional assessments. In a meta-analysis by Dominguez, a correlation between cognitive domains and four symptom dimensions (positive, negative, depressive, and disorganized) was assessed.[6] Negative symptoms were found to be most strongly correlated with verbal fluency, verbal learning and memory, and IQ.

Conscious evaluation and self-reflection are postulated to be the cognitive processes that can be attributed to the evolution of insight.[7] Research has shown that insight requires a wide range of inputs from various neurocognitive functions predominantly involving frontal and parietal cortex.[8] Reduced functioning of the prefrontal cortex also has been postulated to lead to impairment in insight.[9] Neurocognitive impairment in one or more components of many intricately linked variables might be responsible for poor insight in patients with schizophrenia.[7] A meta-analysis by Aleman et al. found a significant correlation between the level of neurocognitive performance and insight among schizophrenic patients.[10] They noted that all tested cognitive domains were correlated with impaired insight to a similar degree. However, there are not many Indian studies assessing the relation of negative symptoms and insight with neurocognitive impairment in schizophrenia.

The assessment of cognitive functioning in patients with schizophrenia thus becomes immensely important not only in understanding the neurobiological correlates of this elusive illness but also in designing modern treatments and rehabilitation programs. This study was conducted in this direction to assess cognitive functioning in patients freshly diagnosed with schizophrenia and to see its correlation with negative symptoms and level of insight.

MATERIALS AND METHODS

This was a hospital-based, cross-sectional, observational study, conducted among patients of the psychiatry department of a tertiary care multispecialty hospital during 2016–17. According to a previous Indian study conducted by Talreja et al. in 2013, 70% of schizophrenia patients were observed to have cognitive dysfunction.[5] The calculated sample size for this study to estimate 95% confidence interval for the occurrence of cognitive dysfunction with a 10% absolute margin of error was 81, and hence, a sample size of 85 was taken. All consecutive freshly detected cases of schizophrenia as per the International Classification of Diseases-10 criteria fulfilling inclusion and exclusion criteria and willing to participate in the study were taken up after informed consent was obtained. All cases aged between 18 and 45 years, after initiation of treatment, and improvement in acute symptoms of psychosis were included. Patients with a history of concomitant medication for any other medical illness and past history of traumatic brain injury or comorbid substance use were excluded.

Sociodemographic data were collected using a specially designed pro forma. Neurocognitive assessment was done using Addenbrooke's Cognitive Examination-III (ACE-III) Scale,[11] Negative symptoms were assessed by positive and negative syndrome scale (PANSS),[12] and insight was assessed by a schedule for the assessment of insight (SAI).[13]

ACE III is an easily administrable screening test to assess cognitive performance. Cognitive domains assessed in ACE-III correlate significantly with standardized neuropsychological tests assessing the domains of attention, language, verbal memory, and visuospatial function. When used for screening of cognitive impairment, ACE-III shows high sensitivity and specificity in detecting cognitive impairment at the recommended cut-off score of 82 (sensitivity = 0.93; specificity = 1.0). Internal reliability as measured by Cronbach's α coefficient is 0.88.

PANSS is a rating scale used for measuring symptom severity in patients with schizophrenia. The components are–positive scale (7 items, each scoring 7, max score of 49), Negative scale (7 items, each scoring 7, max score of 49) and General psychopathology scale (16 items, each scoring 7, max score of 112). The scale has shown high internal reliability and homogeneity among PANSS items, with coefficients ranging from 0.73 to 0.83. SAI is used to rate insight in patients with psychosis, administered by a clinician or a trained rater and covers three overlapping dimensions, namely awareness of illness, capacity to evaluate the psychotic experiences as abnormal and treatment compliance. Each dimension has two or three questions scored from 0 = “never” to 2 = “often,” with a maximum total score of 14.

Data analysis was carried out using SPSS (Statistical Package for Social Sciences, IBM, 2020, USA) Version 20:0. Qualitative data variables were expressed by using frequency and percentage (%). Quantitative data variables were expressed by using mean and standard deviation. Pearson's correlation coefficient was used to find the correlation between ACE III score, PANSS (N) score and SAI score. Chi-square test/Fisher's exact test was used to find the association between two qualitative data variables. Unpaired t-test was used to find the significant difference between mean score within two independent groups. P < 0.05 was considered as significant and <0.005 was considered highly significant.

RESULTS

Fifty-three (62.4%) were males, the age range was 19–41 years with a mean age of 28.1 years, 66 (77.6%) had ≤10 completed years of formal education, 56 (65.9%) of them were unemployed, 53 (62.4%) were married, and another 19 (22.4%) were living separately from their spouses.

With an ACE III cutoff score of 82, 34 (40%) subjects were found to have cognitive dysfunction. Cognitive dysfunction was found to have a significant statistical association with negative symptoms (PANSS (N) score) [Table 1]. Cognitive dysfunction was also found to have a significant statistical association with insight scores (SAI) [Table 2].

Table 1

Association of cognitive dysfunction with negative symptoms

ACE III score	Number of patients	PANSS (N) score, mean±SD	P
≥82	51	16.53±2.73	0.003
<82	34	18.65±3.28

ACE – Addenbrooke’s Cognitive Examination; PANSS – Positive and Negative Syndrome Scale; SD – Standard deviation

Table 2

Association of cognitive dysfunction with insight

ACE III score	Number of patients	SAI score, mean±SD	P
≥82	51	7.55±1.28	<0.001
<82	34	6.68±1.45

ACE – Addenbrooke’s Cognitive Examination; SD – Standard deviation; SAI – Schedule for the assessment of insight

There were no statistically significant differences between the groups when cognitive dysfunction was compared with gender and age, but a significant difference was noted with the level of education, marital status, and occupational status.

The score attained by each individual on the five domains of ACE III was converted into percentage of respective maximum score. Summary of the data is shown in Table 3. The same is represented in box and whisker plot in Figure 1.

Table 3

Percentage scores on the five domains of Addenbrooke’s Cognitive Examination-III

	Attention	Memory	Language	Fluency	Visuospatial
Minimum	61.1	46.2	26.9	50.0	56.3
Maximum	100.0	100.0	100.0	100.0	100.0
Mean±SD	82.2±9.9	73.5±14.7	94.1±14.4	80.8±27.3	86.8±11.0

SD – Standard deviation

Figure 1

Percentage scores on the five domains of Addenbrooke's Cognitive Examination -III

Correlation of cognitive functioning with negative symptoms and insight was carried out using Spearman correlation coefficient and noted to be highly significant [Table 4 and Figures 2 and 3]. This implies that better cognitive function after the first episode of schizophrenia correlated with less negative symptoms and better insight into the illness.

Table 4

Correlation of cognitive dysfunction with negative symptoms and insight

ACE III score	PANSS (N) score	SAI score
Correlation coefficient	−0.438	0.371
P	<0.001	<0.001
n	85	85

ACE – Addenbrooke’s Cognitive Examination; PANSS – Positive and Negative Syndrome Scale; SAI – Schedule for the assessment of insight

Figure 2

Correlation of cognitive dysfunction with negative symptoms

Figure 3

Correlation of cognitive dysfunction with insight

DISCUSSION

In this study, cognitive dysfunction was observed in 34 (40%) out of the total 85 patients, based on the sensitive cutoff score of 82 of ACE III. This study showed impairment across all the five cognitive domains assessed. Maximum dysfunction was observed in the memory domain followed by fluency domain and language domain was relatively well preserved.

A study by Gonzalez on 111 patients with first-episode schizophrenia (n = 86) and schizoaffective disorder (n = 25) showed that 77% had cognitive dysfunction.[14] A study by Reichenberg in patients with first-episode psychosis showed a prevalence of neuropsychological abnormality ranging between 16% and 45% in patients with schizophrenia, depending on the criterion employed for defining cognitive dysfunction.[15] When all criteria are taken together, 85% of the schizophrenia group showed cognitive dysfunction. But among first-episode psychosis cases using Mini-Mental Status Examination, Tatari showed that 75.8% of patients had definite cognitive impairment, 12.9% showed possible impairment, and only 11.3% showed no cognitive impairment.[16] A study in the Indian population by Talreja et al., using the ACE-R Scale (previous version of ACE III), yielded a similar result showing that 70% of patients with schizophrenia had cognitive dysfunction.[5]

Hoff analyzed neuropsychological functioning of first-episode schizophrenia patients and found no difference between the male and female group.[17] However, the study conducted by Srinivasan et al. in Indian patients showed a difference in cognitive performance between the gender.[18] In this study, no significant difference in the cognitive function was observed between males and females similar to the above-quoted study by Hoff. This variance may be due to the fact that it was conducted in patients with chronic schizophrenia and used a variety of batteries for cognitive assessment.

Addington et al. studied first-episode psychosis and observed no significant association between age at onset of illness and cognitive function.[19] Krishnadas studied Indian patients with schizophrenia in remission (with a mean duration of illness 11.3 ± 5.8 years) and noted no relation between neurocognition and age.[20] In this study, no significant difference in the cognitive function was also observed among different age groups.

Swanson found that patients with schizophrenia who were in the higher education group performed better in cognitive testing.[21] In his study, a significant difference in educational attainment was observed between patients with cognitive dysfunction and others. Patients with better cognitive function showed higher educational attainment.

Deficits in interpersonal skills and work skills resulting from cognitive dysfunction may influence a patient's ability to get married and stay in the marriage.[22] In developed countries, where finding a partner involves interpersonal skills, persons with schizophrenia are observed to have low rates of marriage. However, in developing countries, where many marriages are arranged by the families, the rates of marriage in this population are as high as around 65% in India. Talreja et al. found no significant association between cognition and marital status, in a study on patients with schizophrenia in the Indian population.[5] In this study, 62.4% were married, which is similar to the above-mentioned study of Srinivasan et al.[18] Those with cognitive dysfunction were found more likely to have marital separation.

The study by Srinivasan et al. had shown that among patients with schizophrenia, cognitive deficits did not relate significantly to current occupation status or to level of performance at work.[18] In this study, 56 (65.9%) were unemployed, and majority of them belonged to the cognitive dysfunction group. A meta-analysis by Mesholam showed that patients with first-episode schizophrenia demonstrated medium-to-large impairments across all tested cognitive domains.[23] A study by Srinivasan et al. in the Indian population which compared cognitive function among chronic patients of schizophrenia demonstrated that they performed poorly on all cognitive tests in comparison to normal controls.[18] In this study, patients showed impairment in all the domains of ACE III, which is in line with the generalized cognitive dysfunction found in the above studies.

Mesholam had demonstrated that in patients with first-episode schizophrenia, immediate verbal memory showed maximum dysfunction.[23] A similar finding was observed in the meta-analysis by Schaefer et al. also.[4] Similarly, a study by Krishnadas found significant impairment in scores of immediate sentence recall, digit span tests, similar and dissimilar pair retention, and visual retention among patients with chronic schizophrenia compared to controls.[20] In this study, maximum dysfunction was observed in the memory domain, which is in keeping with existing literature.

In the MATRICS Consensus Cognitive Battery, the test for category fluency is used as an indicator of speed of processing.[24] A study by Beilen observed that in patients with schizophrenia, the verbal fluency was predicted by psychomotor speed but not by memory or executive functioning.[25] Meta-analyses by Mesholam and Schaefer et al. observed that the domain of processing speed also showed high dysfunction along with memory.[234] The meta-analysis by McCleery found that patients with first-episode schizophrenia exhibited marked impairment in the speed of processing.[26] The study by Shakeel on Indian patients with chronic schizophrenia using computer-based paced semantic verbal fluency test showed that patients with schizophrenia scored significantly inferior to healthy controls.[27] In this study, the fluency domain showed significant dysfunction similar to the above studies.

A review by Radanovic observed that in comparative studies of language impairment in schizophrenia and aphasia, both the groups performed similarly on tasks of language comprehension, naming, and repetition with the presence of abundant semantic paraphasias.[28] A meta-analysis by Mesholam of studies assessing language dysfunction showed a moderately large effect size of −0.88 with individual test effect sizes ranging from −1.2 to −0.67.[23] It also showed that studies involving a higher percentage of first-episode schizophrenia patients taking antipsychotic medication showed smaller effect sizes. A meta-analysis by Schaefer et al. showed an effect size of −0.68 for verbal ability.[4] In this study, language was observed to be relatively unimpaired, compared to other domains.

Rabinowitz observed a significant negative correlation between cognitive function and negative symptoms.[29] Dominguez demonstrated that negative symptoms were most strongly correlated with cognitive deficits in domains of verbal fluency, verbal learning, and memory.[6] In this study, a highly significant negative correlation was observed between cognitive function and negative symptoms, which is similar to existing literature, implying that better cognitive function after the first episode of schizophrenia correlated with less negative symptoms.

A meta-analysis by Aleman et al. showed a positive correlation between cognitive functioning and insight.[10] A study by Parellada in freshly diagnosed schizophrenia spectrum disorders showed that poorer baseline executive functioning was associated with worse insight.[30] In this study also, highly significant positive correlation was observed between cognitive function and insight which is similar to existing literature. This finding implies that better cognitive function after the first episode of schizophrenia is correlated with better insight.

Based on the findings of this study, it is recommended that health professionals should be made aware that cognitive dysfunction is common among those suffering from schizophrenia, even at initial presentation. Those diagnosed with schizophrenia should be assessed for cognitive function early in the course of the illness. This will help facilitate prompt interventions directed at insight and cognitive rehabilitation. Assessment of cognitive functioning is strongly advocated to be done in these cases by using easily administrable tools like ACE III and this shall become part of a standard treatment protocol.

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Conflicts of interest

There are no conflicts of interest.