Correlation of neurocognitive deficits with positive and negative symptoms in schizophrenia.

BACKGROUND: Patients with schizophrenia manifests a broad array of cognitive impairments, including impaired performance on measures reflecting attention, information processing, executive functions, memory, and language capabilities. AIM: This study aims to assess neurocognitive deficits and their correlation with positive and negative symptoms in patients with schizophrenia.
MATERIALS AND METHODS: Sample was collected from private clinic of Jabalpur, Bhopal, and Patna. Selection of sample was purposive sampling. The sample size consists of 60 diagnosed cases of schizophrenia on the basis of (International Classification of Diseases-10 [ICD-10] Diagnostic Criteria for Research criteria) and 30 normal controls. Annet's Hand Preference Battery was used to screen handedness and only right-handed male were included in this study. After screening according to inclusion and exclusion criteria, 60 diagnosed (ICD-10 criteria) schizophrenia patients were selected which was further divided into two groups on the basis of positive and negative syndrome scale, i.e. schizophrenia with positive and negative symptoms. Thirty matched normal controls having scores <2 scores on General Health Questionnaire-12 were selected for the study. After filling of sociodemographic details Luria-Nebraska Neuropsychological Battery (LNNB-I) was administered on both schizophrenia group and normal control.
RESULTS: Cognitive functions are severely impaired in schizophrenia compared to normal control and within schizophrenia groups negative schizophrenia had poor performance on LNNB-I than positive schizophrenia. Regarding the correlation of neurocognitive deficits, both schizophrenia groups were correlated but negative symptoms of schizophrenia were strongly correlated with neurocognitive deficits.
CONCLUSION: Cognitive functions are severely impaired in schizophrenia as compared to normal control and within schizophrenia groups, negative schizophrenia had poor performance on LNNB-I than positive schizophrenia. Regarding the correlation of neurocognitive deficits, both schizophrenias groups were correlated but negative symptoms of schizophrenia were strongly correlated with neurocognitive deficits. Copyright:

Patients with schizophrenia manifest a broad array of cognitive impairments, including impaired performance on measures reflecting attention, information processing, executive functions, memory, and language capabilities. The exact timing of onset of cognitive impairment during the early phase of schizophrenia and its progress and course after the first episode is unclear. Moreover, the clinical importance of impaired cognitions in first-episode schizophrenia is unclear, and it may predate the onset of disorder.[1] Numerous studies have reported deficits in attention, memory and executive functioning that are now thought to be strongly related to clinical outcome, perhaps more than are positive and negative symptoms. Cognitive deficits can manifest as an inability accurately to recognize social cues or to retrieve appropriate responses.[234] Neurocognitive and social impairments are often present long before the onset of schizophrenia. The associations between cognitive and social functioning suggest that cognitive impairment may be an important predictor of outcome in schizophrenia.[5678] The relevance of the present study is that only a limited number of studies have assessed the correlation of neurocognitive deficits with positive and negative symptoms in schizophrenia using Luria-Nebraska Neuropsychological Battery (LNNB-I). Identification of the neurocognitive deficits in Schizophrenia can further help in neurocognitive rehabilitation. It is possible that improved cognitive functioning will result automatically in concomitant improvements in social and vocational adjustment. For example, increased ability to focus attention may permit patients with both premorbid and morbid social skills to acquire new skills spontaneously. In view of the above, the study was undertaken to assess and correlate neurocognitive deficits with positive and negative symptoms in schizophrenia. The present work has a great potential in improving the life skills as well as social adjustment of schizophrenia patients.

MATERIALS AND METHODS

This was a prospective, cross-sectional, analytical study done under postdoctorate fellowship for women candidates from University Grants Commission. The study was carried out at private clinics at Jabalpur, Bhopal, and Department of Psychology, Patna University. Permission for the study was obtained from the Institutional Ethical Committee. Written informed consent was taken from all subjects.

Sample

The sample was collected from private clinic of Jabalpur, Bhopal, and Patna. Selection of sample was by purposive sampling. The sample size consists of 60 (30 each with positive and negative symptoms) newly diagnosed patients of schizophrenia on the basis of International Classification of Diseases-10 Diagnostic Criteria for Research (ICD-10 DCR) criteria[9] and 30 age- and sex-matched normal control subjects. Patients were drug naïve at the time of evaluation. The patients in both groups were free from any comorbid psychiatric condition including substance abuse or dependence (except nicotine and caffeine), serious medical or neurological disorders as assessed by history, physical examination, and laboratory investigations.

Inclusion criteria for schizophrenia patients

Diagnosed case of schizophrenia (according to ICD-10 DCR)

At least 2 years of duration of illness

Age range between 20 and 50 years

Educated up to primary level

Only right-handed male schizophrenia patients were selected.

Exclusion criteria for schizophrenia patients

Comorbid psychiatric disorder

Visual and hearing impairment

History suggesting organic pathology, substance abuse, and significant physical illness

Illiterate patients

Noncooperative patients.

Inclusion criteria for normal controls

Age range between 20 and 50 years

Educated up to primary level

Only right-handed male subjects were selected

Co-operative normal was selected.

Exclusion criteria for normal controls

Comorbid psychiatric disorder and physical illness

Score >2 on the General Health Questionnaire (GHQ)

Vision and hearing impairment

Illiterate.

Tools for assessment

Sociodemographic and clinical datasheet

It is a semi-structured pro forma especially designed for this study. It contains information about sociodemographic variables such as age, sex, religion education, marital status, domicile and occupation, and clinical details, for example, age of onset, mode of onset, course, duration, medication, and side effects.

Hand Preference Battery

Annett's Hand Preference Battery (1970) consists of 6 items. If all 6 items are performed by right hand the person is classified as right-handed, if by left hand the person is classified as left-handed and mixed performance is considered as mixed-handedness.[10]

General Health Questionnaire-12

The GHQ is a standardized, self-administered screening test designed for a quick and easy identification of possible psychiatric cases in the target population. It is now well-established that the scores of the GHQ correlate highly with blind, independent assessments. The GHQ originally consisted of 60 items. For the present study, GHQ-12 will use as a screening test. It inquires about symptoms during the “past few weeks” and provides for responses in four categories.[11]

Positive and negative syndrome scale

The positive and negative syndrome scale (PANSS) was developed in 1987 to assess clinical symptoms of schizophrenia. The PANSS includes 30 items on three subscales: 7 items covering positive symptoms (e.g. delusions and hallucinations), 7 items covering negative symptoms (e.g. social withdrawal, flat affect, lack of motivation), and 16 items covering general psychopathology (e.g. anxiety, depression). The ratings can be completed in 30–40 min. Each item is scored on 10 rating scales in schizophrenia. 7-point Likert scale ranging from 1 to 7. Therefore, the positive and negative subscales each range from 7 to 49, and the general psychopathology subscale from 16 to 112.[12]

Luria-Nebraska Neuropsychological Battery-I

The LNNB-I is a multidimensional battery designed to assess a broad range of neuropsychological functions. It consists of 269 items it is based on the basic functions involved these items are arranged under eleven clinical scales, 5 summary scales, 8 localization scales, and 28-factor scales.[13]

Procedure

After screening according to inclusion and exclusion criteria, 60 diagnosed (ICD-10 DCR criteria) schizophrenia patients were selected which was further divided into two groups on the basis of PANSS, i.e., schizophrenia with positive and negative symptoms. Annet's Hand Preference Battery was used to screen handedness. On the basis of GHQ-12, 30 normal controls having scores <2 scores were selected for the study. After filling of sociodemographic details LNNB-I was administered on both schizophrenia group and normal control.

Statistical analysis

The collected data were analyzed with the help Statistical Package for Social Sciences 22 Version (SPSS-22, IBM, Chicago, USA) and appropriate statistics were computed. Analyses were performed with a significance level of <0.05, <0.01 level and a confidence level of 95% and 99%, respectively.

RESULTS

The study included 30 male patients with positive schizophrenia, 30 male patients with negative schizophrenia and 30 age- and sex-matched normal control subjects. All the subjects hailed from urban background. All the patients with schizophrenia were married, but among normal controls 20 were married and 10 were unmarried (Fishers exact test P = 0.00001576; significant).

The mean age and education are given in Table 1. There was no significant differences between the three groups in respect to age and education.

Table 1

Sociodemographic details of normal controls and patients with positive and negative schizophrenia

Variable	Mean±SD			F-test	P
	Normal	Positive schizophrenia	Negative schizophrenia
Age	32.40±7.91	32.43±4.53	28.80±8.94	2.40	NS
Education	13.40±3.92	12.86±1.83	12.03±2.05	1.85	NS

SD – Standard deviation, NS – Not significant

Comparison between normal controls and schizophrenia patients on LNNB-I show significant difference at 0.01 level and 0.05 levels on all the scales of LNNB-I [Table 2]. Comparison of normal controls, positive schizophrenia, and negative schizophrenia on LNNB-I scale shows that there was a significant difference between the three groups on all the scales of LNNB-I [Table 3].

Table 2

Luria-Nebraska Neuropsychological Battery-I scores of normal (n=30) and schizophrenia (n=60) subjects

LNNB scales	Mean±SD		t-test
	Normal	Schizophrenia
Motor functions (C1)	31.73±3.40	46.23±12.79	6.085*
Rhthym functions (C2)	34.40±7.77	48.18±14.87	4.753*
Tactile functions (C3)	34.63±5.58	46.00±8.43	6.67*
Visual functions (C4)	44.93±7.08	55.68±11.95	4.537*
Receptive speech (C5)	34.40±7.77	48.18±14.87	4.753*
Expressive speech (C6)	34.13±6.02	43.10±13.28	3.514*
Writing (C7)	38.20±9.92	45.83±12.15	2.977*
Reading (C8)	38.30±6.09	45.46±9.49	3.758*
Arithmetic (C9)	40.43±7.26	50.45±17.68	2.973*
Memory functions (C10)	34.80±8.06	52.90±15.82	5.883*
Intellectual functions (C11)	42.00±9.45	53.36±14.15	3.973*

*Significant at 0.05 levels. SD – Standard deviation, LNNB – Luria-Nebraska Neuropsychological Battery

Table 3

Luria-Nebraska Neuropsychological Battery-I scores of normal (n=30) control, positive schizophrenia (n=30) and negative schizophrenia (n=30) patients

LNNB scales	Mean±SD			F-test
	Normal	Positive schizophrenia	Negative schizophrenia
Motor functions (C1)	31.73±3.40	42.5±7.96	49.9±15.5	23.95*
Rhthym functions (C2)	34.40±7.77	44.03±9.52	52.33±17.98	15.26*
Tactile functions (C3)	34.63±5.58	43.76±6.64	48.23±9.58	26.08*
Visual functions (C4)	44.93±7.08	54.80±12.51	56.56±11.50	10.43*
Receptive speech (C5)	34.40±7.77	44.03±9.52	52.33±17.98	15.26*
Expressive speech (C6)	34.13±6.02	39.63±8.98	46.56±15.91	9.43*
Writing (C7)	38.20±9.92	43.70±9.05	47.96±14.46	5.53*
Reading (C8)	38.30±6.09	42.83±5.26	48.10±11.89	10.49*
Arithmetic (C9)	40.43±7.26	43.83±5.26	57.20±21.9	11.96*
Memory functions (C10)	34.80±8.06	49.83±12.20	55.96±18.46	19.23*
Intellectual functions (C11)	42.00±9.45	50.06±9.81	56.66±16.98	10.23*

*Significant at 005 levels. SD – Standard deviation, LNNB – Luria-Nebraska Neuropsychological Battery

Table 4 describes the correlation between all the measures of LNNB-I and positive and negative symptoms of schizophrenia it was been observed that both positive and negative schizophrenias group were significantly correlated on (C1), (C2), (C5), (C9), (C10), (C11) scales; only positive schizophrenia was significantly correlated with C3 and C8 scales while only negative schizophrenia was significantly correlated with C4, C6, and C7 scales.

Table 4

Correlation between all measures of Luria-Nebraska Neuropsychological Battery-I and positive and negative symptoms of schizophrenia

LNNB-I scales	Positive symptoms correlation value (R)	Negative symptoms correlation value (R)
Motor function (C1)	0.613**	0.649**
Rhythm function (C2)	0.537**	0.378*
Tactile function (C3)	0.567**	0.350
Visual function (C4)	0.225	0.379*
Receptive function (C5)	0.537**	0.378*
Expressive function (C6)	0.236	0.745**
Writing (C7)	0.273	0.690**
Reading (C8)	0.693**	0.293
Arithmetic (C9)	0.548**	0.429*
Memory function (C10)	0.444*	0.492**
Intellectual function (C11)	0.495**	0.692**

*Correlation is significant at level 0.05, **Correlation is significant at level 0.01. LNNB-I – Luria-Nebraska Neuropsychological Battery-I

DISCUSSION

Socio-demographic details

Results of sociodemographic details show that all the three groups were well matched on age and education, as indicated by statistical analysis. This is a strength of the study because education variables are considered to influence cognitive functioning the most.

Comparison schizophrenia and normal controls on Luria-Nebraska Neuropsychological Battery-I

It has been postulated that the cognitive deficits seen in schizophrenia patients are the core features of the disorder.[14] Attention, memory, reasoning, and processing speed are the primary cognitive deficits in schizophrenia. The cognitive deficits are the major reason for the development of impaired social, occupational, and economic functioning and thus are important targets in therapy.[15] On LNNB-I the three groups differed from each other on all the scales of the LNNB-I. Furthermore, the negative schizophrenia subjects had poorer performance in comparison to positive schizophrenia subjects and normal control. All the LNNB scale variables discriminate significantly between the groups [Table 3]. The poorer performance of the schizophrenia patients in comparison to normal control subjects is in consonance with the findings that individuals with schizophrenia show impaired performance on all tests sensitive to frontal lobe.[16]

The findings of the present study are in agreement with an earlier Indian study which compared chronic schizophrenia patients to normal individuals and concluded that patients with schizophrenia performed poorly in all cognitive tests. Cognitive deficits in patients were related to gender education, age, duration of illness, and presence of positive and negative symptoms. Cognitive deficits are common with schizophrenias which later affects their daily functioning activities. Highly significant difference (P < 0.0001) was found between the cognitive functions of the schizophrenia group and healthy control. Cognitive deficits exist even in the stable patients of schizophrenia which is significantly higher than the healthy group.[17] Meha et al. also had similar findings in their study.[18]

Comparison of positive and negative schizophrenia with normal controls on Luria-Nebraska Neuropsychological Battery-I

On comparison with normal controls, schizophrenia patients showed significant neurocognitive deficits on LNNB-I scale. Further analysis of the results revealed that negative schizophrenia patients showed poor performance in contrast to positive schizophrenia patients and normal controls. The current study implies that negative symptoms and cognitive symptoms shared significant common variances. In other words, negative schizophrenia patients showed poor performances on LNNB-I specifically on almost all the scales. In normal aging and many neuropsychiatric disorders including schizophrenia, the pattern of cognitive deficits is decreased levels of learning over multiple exposure trials and reduced recall of learned information.[1920] Liu et al. also reported similar findings that Schizophrenia is associated with impairment in prospective memory compared to healthy controls. They have a poor ability to remember to carry out an intended action in the future.[21]

Link between neurocognitive deficits and positive and negative symptoms in schizophrenia

The positive and negative schizophrenias are correlated with neurocognitive deficits which indicate a causative link between neurocognitive deficits and positive symptoms in schizophrenia patients which implies a relationship between low cognitive functioning and psychosis. A dominant view about the etiology of schizophrenia is the neurodevelopmental hypothesis, which suggests that schizophrenia arises from early, possibly fetal abnormalities of genetic and/or environmental origin.[22] Negative schizophrenias were strongly positively correlated with neurocognitive deficits on LNNB-I in the area of receptive speech (C5) expressive speech (C6), arithmetic (C9) memory (C10), and intellectual functions (C11) in the present study. The findings of the present study are consistent with the study of Harvey et al. which reported that negative symptoms and cognitive deficits in schizophrenia share many features and are also correlated in their severity.[23] The reason of strong correlation with positive symptoms may be due to the fact that positive psychotic symptoms may fluctuate during the course of the illness, while negative symptoms and cognitive defects are fairly unchanged.[24] Mazza et al. 2013 assessed the anterior and posterior attention systems in schizophrenia patients using two tasks: A dual-task paradigm evaluating executive functions, especially planning and coordination, along with a Simon task evaluating automatic shifting of visual attention. Results revealed that negative schizophrenias have a deficit that affects the functioning of both anterior and posterior attention systems. On the other hand, positive schizophrenia patients showed a selective deficit only for the posterior attention system, with a pattern that is in the opposite direction compared to that of negative schizophrenia.[25] Thus, deficits in both anterior and posterior attention systems could explain the poorer performance of schizophrenia patients on LNNB. Andreasen and Crow mentioned in their initial studies that individuals with schizophrenia who had predominantly negative symptoms evidenced more cognitive impairment than those patients with predominantly positive symptoms.[26] As shown in Table 4, it is obvious that positive schizophrenia is correlated with C8 reading functions. This finding is congruent with the findings of an earlier study which also observed that patients with schizophrenia show severe deficits in reading ability. They opined that this represents a potentially remediable cause of impaired socioeconomic function. Such deficits are not presently identified during routine clinical assessment. Deficits most likely develop during the years immediately around illness onset and may contribute to the reduced educational and occupational achievement associated with schizophrenia.[27] Lin et al. found clinical (mainly negative) symptoms to be a mediator of the influence of neurocognition and social cognition on functional outcome of schizophrenia.[28] According to Hofer et al. cognitive deficits in schizophrenia is the strongest predictor of poor long term outcome. They reported associations between severity of cognitive deficits and social dysfunction, impairments in independent living, occupational limitations, and disturbances in quality of life.[29] Thus the present study demonstrates the link between neurocognitive dysfunction and positive and negative symptoms in schizophrenias.

Limitations

The study has few limitations. The sample size was small and study was conducted only on male right-handed schizophrenias patients so there are problems with generalization of the study.

CONCLUSION

Patients with schizophrenia exhibit severely impaired cognitive functions as compared to normal control and within schizophrenia groups, negative schizophrenia had poor performance on LNNB-I than positive schizophrenia. Regarding correlation of neurocognitive deficits, both schizophrenias groups were correlated but negative symptoms of schizophrenia were strongly correlated with neurocognitive deficits. Neurocognitive rehabilitation as well as vocational training of schizophrenia patients, especially those with negative symptoms, may improve its functional outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.