Cognitive dysfunction and negative symptoms in patients with schizophrenia and their first-degree relatives from simplex and multiplex families

Figures & data

Table 1 Demographics of subjects included in this study

Demographic parameter	SPM (n=23)	SPS (n=21)	CONP (n=14)	RPM (n=26)	RPS (n=52)	CONR (n=29)
Age (year)	29.8 (9.8)*	22.5 (7.6)	22.9 (10.9)	45.3 (13.8)	38.9 (14.1)	39.8 (13.0)
Mean (SD)
Education years	10.0 (2.9)	10.8 (2.4)	10.6 (2.8)	7.7 (3.7)**	10.0 (3.4)	9.8 (2.6)
Mean (SD)
Male:female	9:14	7:14	7:7	13:13	22:30	13:16
Duration, years	6.9 (5.2)	4.5 (3.7)	–	–	–	–
Mean (SD)

Note:

* The average age of SPM groups is higher than the age of SPS and CONP groups. (P=0.012, P=0.033).

** The average education years of RPM groups is less than that of RPS and CONR groups. (P=0.004, P=0.015).

Abbreviations: SPM, patients from multiplex families; SPS, patients from simplex families; CONP, control proband; RPM, relative of patients from multiplex families; RPS, relative of patients from simplex families; CONR, relative of control proband.

Table 2 Results of cognitive testing and negative symptom assessment in probands of patients with schizophrenia and controls

Neuropsychological measures & negative symptoms	SP (n=44)		CONP (n=14)		F (df=1)	P-value
	M	SD	M	SD
Abstraction
VS	49.6	20.9	60.6	12.8	3.107	0.083
Short-time working memory
MS
Digit span	10.6	3.0	11.4	2.8	0.103	0.749
Word span	7.5	2.2	8.8	2.5	0.010	0.920
Spatial span	6.3	2.1	7.3	2.6	1.208	0.276
Executive function
WCST
Total cards	84.5	28.0	64.0	21.3	1.670	0.202
Correct numbers	23.2	5.3	25.0	0.0	6.588	0.013
Perseverative errors	22.5	12.1	18.3	8.4	1.632	0.207
Random errors	38.8	25.7	20.7	14.9	3.155	0.081
Correct categories	4.6	1.1	5.0	0.0	7.884	0.007
Continuous attention
CPT
Visual errors	55.1	14.4	47.8	5.7	6.826	0.012
Visual omission	67.8	18.0	49.0	3.4	64.987	0.000
Visual reaction time	58.6	15.3	46.5	5.9	8.679	0.005
Acoustic errors	61.0	16.4	48.5	5.3	14.071	0.000
Acoustic omission	69.9	19.0	53.5	10.9	20.959	0.000
Acoustic reaction time	54.9	14.1	45.8	6.5	5.892	0.018
Negative symptoms
N1	2.8	1.2	1.2	0.4	15.399	0.000
N2	2.5	1.4	1.1	0.3	30.442	0.000
N3	2.3	1.0	1.1	0.5	12.860	0.001
N4	2.6	1.3	1.1	0.3	21.954	0.000
N5	3.2	1.8	1.6	0.9	7.510	0.008
N6	2.4	1.5	1.0	0.0	34.502	0.000
N7	1.8	1.1	1.1	0.5	9.165	0.004
Total	17.2	7.3	8.3	0.7	26.435	0.000

Note: df=1.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; MS, memory span from Multiple Memory Assessment Scale; WCST, Wisconsin Card Sorting Test; CPT, Continuous Performance Test; SP, patients with schizophrenia; CONP, control proband; M, mean.

Table 3 Results of cognitive testing and negative symptom assessment in relatives of patients with schizophrenia and controls

Neuropsychological measures & negative symptoms	RP (n=78)		CONR (n=29)		F(df=1)	P-value
	M	SD	M	SD
Abstraction
VS	49.9	18.6	62.6	11.2	5.136	0.025
Short-time working memory
MS
Digit span	10.2	2.5	10.6	2.1	0.373	0.543
Word span	7.3	1.4	7.7	1.6	0.004	0.950
Spatial span	6.4	2.1	6.2	1.4	2.912	0.091
Executive function
WCST
Total cards	81.9	28.4	68.9	23.2	2.674	0.105
Correct numbers	24.2	3.3	25.0	0.0	6.287	0.014*
Perseverative errors	22.9	12.6	18.3	8.7	2.008	0.159
Random errors	35.3	22.7	25.8	18.0	2.605	0.110
Correct categories	4.8	0.8	5.0	0.0	8.325	0.005*
Continuous attention
CPT
Visual errors	49.6	7.0	50.2	9.7	0.585	0.446
Visual omission	58.0	14.7	51.1	8.4	15.156	0.000*
Visual reaction time	49.9	9.2	47.0	6.2	4.126	0.045*
Acoustic errors	50.5	9.1	50.1	5.7	2.301	0.132
Acoustic omission	61.5	16.8	56.9	15.8	0.918	0.340
Acoustic reaction time	48.8	9.7	44.8	9.4	0.012	0.914
Negative symptoms
N1	1.4	0.7	1.2	0.4	16.608	0.000*
N2	1.3	0.7	1.1	0.3	14.849	0.000*
N3	1.5	0.7	1.2	0.4	11.127	0.001*
N4	1.3	0.6	1.0	0.2	23.534	0.000*
N5	2.7	1.4	2.0	0.9	4.756	0.031*
N6	1.4	0.8	1.0	0.2	28.667	0.000*
N7	1.2	0.6	1.1	0.4	4.229	0.042*
Total	10.9	3.8	8.7	1.8	9.097	0.003*

Notes:

* df=1. P<0.05 between RP and CONR group.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; MS, memory span from Multiple Memory Assessment Scale; WCST, Wisconsin Card Sorting Test; CPT, Continuous Performance Test; RP, relatives of patients; CONR, relatives of control proband.

Table 4 Results of cognitive testing and negative symptom assessment in patients with schizophrenia from simplex families and multiplex families and controls

Neuropsychological measures & negative symptoms	SPM (n=23)		SPS (n=21)		CONP (n=14)		SPM vs CONP	SPS vs CONP	SPM vs SPS
	Mean	SD	Mean	SD	Mean	SD	P1	P2	P3
Abstraction
VS	45.8	4.2	53.8	4.3	60.4	5.2	0.042	>0.05	>0.05
Short-time working memory
MS
Digit span	9.7	0.6	11.8	0.6	11.2	0.7	>0.05	>0.05	0.049
Word span	6.5	0.5	8.6	0.5	8.8	0.6	0.001	>0.05	0.006
Spatial span	6.2	0.5	6.5	0.5	7.2	0.6	>0.05	>0.05	>0.05
Executive function
WCST
Total cards	86.7	5.7	81.4	5.9	65.2	7.1	0.007	0.041	>0.05
Correct numbers	23.5	1.0	23.2	1.0	24.5	1.2	>0.05	>0.05	>0.05
Perseverative errors	23.7	2.5	21.1	2.5	18.5	3.1	>0.05	>0.05	>0.05
Random errors	39.5	5.1	37.1	5.2	22.2	6.3	0.013	0.035	>0.05
Correct categories	4.7	0.2	4.6	0.2	4.9	0.2	>0.05	>0.05	>0.05
Continuous attention
CPT
Visual errors	58.6	2.8	51.5	2.8	48.4	3.5	>0.05	>0.05	>0.05
Visual omission	65.9	3.5	69.5	3.6	49.6	4.3	0.013	0.001	>0.05
Visual reaction time	56.5	3.0	60.6	3.1	47.0	3.7	>0.05	0.004	>0.05
Acoustic errors	63.8	3.2	58.4	3.3	50.1	5.7	0.016	>0.05	>0.05
Acoustic omission	69.3	3.9	70.6	3.9	53.6	4.8	0.021	0.003	>0.05
Acoustic reaction time	57.0	2.8	52.7	2.9	45.8	3.5	0.039	>0.05	>0.05
Negative symptoms
N1	2.8	0.2	2.8	0.2	1.2	0.3	0.003	0.002	>0.05
N2	2.6	0.3	2.4	0.3	1.1	0.3	0.008	0.009	>0.05
N3	2.3	0.2	2.4	0.2	1.1	0.2	0.007	0.005	>0.05
N4	2.6	0.3	2.6	0.3	1.1	0.3	0.002	0.002	>0.05
N5	3.4	0.3	2.9	0.4	1.7	0.4	0.012	>0.05	>0.05
N6	2.4	0.3	2.4	0.3	1.0	0.4	0.008	0.006	>0.05
N7	1.9	0.2	1.8	0.2	1.2	0.3	>0.05	>0.05	>0.05
Total	17.5	1.9	16.7	1.6	9.3	1.9	0.003	0.003	>0.05

Notes: P1: SPM vs CONP, P2: SPS vs CONP, P3: SPM vs SPS. Bold values represent P<0.05.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; MS, memory span from Multiple Memory Assessment Scale; WCST, Wisconsin Card Sorting Test; CPT, Continuous Performance Test; SPM, patients from multiplex families; SPS, patients from simplex families; CONP, control proband.

Table 5 Results of cognitive testing and negative symptom assessment in relatives of patients with schizophrenia from simplex families and multiplex families and controls

Neuropsychological measures & negative symptoms	RPM (n=26)		RPS (n=52)		CONR (n=29)		RPM vs CONR	RPS vs CONR	RPM vs RPS
	Mean	SD	Mean	SD	Mean	SD	P4	P5	P6
Abstraction
VS	48.9	2.6	51.3	1.8	60.9	2.3	0.005	0.002	>0.05
Short-time working memory
MS
Digit span	9.6	0.4	10.6	0.3	10.4	0.3	>0.05	>0.05	0.026
Word span	7.1	0.2	7.5	0.2	7.6	0.2	>0.05	>0.05	>0.05
Spatial span	6.2	0.4	6.6	0.3	6.1	0.3	>0.05	>0.05	>0.05
Executive function
WCST
Total cards	78.9	5.0	82.4	3.4	70.6	4.6	>0.05	0.019	>0.05
Correct numbers	23.9	0.5	24.2	0.4	24.9	0.5	>0.05	>0.05	>0.05
Perseverative errors	23.7	2.2	22.2	1.5	20.0	2.0	>0.05	>0.05	>0.05
Random errors	33.2	4.1	35.7	2.8	27.0	3.8	>0.05	0.044	>0.05
Correct categories	4.7	0.1	4.9	0.1	5.0	0.1	>0.05	>0.05	>0.05
Continuous attention
CPT
Visual errors	52.1	1.6	48.3	1.1	50.2	1.4	>0.05	>0.05	0.027
Visual omission	63.5	2.5	55.1	1.7	51.5	2.3	0.000	>0.05	0.004
Visual reaction time	52.3	1.6	48.5	1.1	47.4	1.5	>0.05	>0.05	>0.05
Acoustic errors	54.3	1.6	48.8	1.3	50.0	1.5	0.024	>0.05	0.003
Acoustic omission	67.2	3.3	58.5	2.2	57.2	3.0	0.015	>0.05	0.019
Acoustic reaction time	51.2	1.9	47.6	1.3	44.8	1.8	0.050	>0.05	>0.05
Negative symptoms
N1	1.7	0.1	1.3	0.1	1.2	0.2	0.018	>0.05	0.047
N2	1.7	0.1	1.2	0.1	1.1	0.1	0.003	>0.05	0.003
N3	1.8	0.1	1.3	0.1	1.2	0.1	0.016	>0.05	0.015
N4	1.5	0.1	1.2	0.1	1.0	0.1	0.028	>0.05	>0.05
N5	3.0	0.2	2.6	0.2	2.0	0.2	0.048	0.017	>0.05
N6	1.6	0.1	1.3	0.1	1.0	0.1	0.049	>0.05	>0.05
N7	1.5	0.1	1.0	0.1	1.1	0.1	0.035	>0.05	0.015
Total	12.0	0.6	10.2	0.4	9.2	0.5	0.001	>0.05	0.014

Notes: P4: RPM vs CONR, P5: RPS vs CONR, P6: RPM vs RPS. Education was included as a covariate in comparisons among the three groups. Follow-up post hoc test (least square differences) was used for the comparisons when overall effects were significant. A value of P<0.05 was considered statistically significant. Bold values represent P<0.05.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; MS, memory span from Multiple Memory Assessment Scale; WCST, Wisconsin Card Sorting Test; CPT, Continuous Performance Test; RPM, relative of patients from multiplex families; RPS, relative of patients from simplex families; CONR, relatives of control proband.

Table 6 Spearman correlational analysis between negative symptoms and scores of neuropsychological measures in patients with schizophrenia

	VS	Digit span	Word span	Spatial span	Total cards	Correct numbers	Perseverative errors	Random errors	Correct categories
r	−0.713**	−0.257	−0.548**	−0.419**	0.464**	−0.394**	0.261	0.463**	−0.394**
	Visual errors	Visual omission	Visual reaction time	Acoustic errors	Acoustic omission	Acoustic reaction time
r	0.314*	0.284	0.368*	0.474**	0.375*	0.473**

Note:

* P<0.05,

** P<0.01.

Abbreviation: VS, vocabulary subtest from Wechsler Adult Intelligence Scale.

Table 7 Spearman correlational analyses between negative symptoms and scores of neuropsychological measures in relatives of patients with schizophrenia

	VS	Digit span	Word span	Spatial span	Total cards	Correct numbers	Perseverative errors	Random errors	Correct categories
r	−0.785**	−0.540**	−0.444**	−0.383**	0.202	−0.045	0.212	0.162	−0.043
	Visual errors	Visual omission	Visual reaction time	Acoustic errors	Acoustic omission	Acoustic reaction time
r	0.105	0.372**	0.380**	0.086	0.147	0.044

Note:

** P<0.01.

Abbreviation: VS, vocabulary subtest from Wechsler Adult Intelligence Scale.

Table 8 Stepwise regression analysis of factors associated with negative symptoms in patients with schizophrenia

Factor	β	SE	Beta	t	P-value
VS	−0.217	0.036	−0.589	−6.064	0.000
WCST correct categories	−12.780	4.021	−1.630	−3.178	0.003
CPT acoustic errors	0.268	0.072	0.583	3.706	0.001
WCST correct numbers	2.442	0.917	1.368	2.663	0.011
CPT visual errors	−0.203	0.084	−0.372	−2.425	0.020

Notes: Standardized regression coefficient: Beta; R²=0.688, F=5.882, P=0.020.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; WCST, Wisconsin Card Sorting Test; CPT, Continuous Performance Test.

Table 9 Stepwise regression analysis of factors associated with negative symptoms in relatives of patients with schizophrenia

Factor	β	SE	Beta	t	P-value
VS	−0.152	0.015	−0.739	−10.203	0.000
CPT visual omission	0.041	0.019	0.159	2.191	0.032

Notes: Standardized regression coefficient: Beta; R²=0.639, F=4.803, P=0.032.

Abbreviations: VS, vocabulary subtest from Wechsler Adult Intelligence Scale; CPT, Continuous Performance Test.