Abstract

Cognitive deficits are core features of schizophrenia and considered putative endophenotypes. This study assessed the familial pattern of deficits in sustained attention, working memory and executive function in remitted-schizophrenia patients and their unaffected siblings. Sixteen patients, 16 unaffected siblings, and 17 healthy control subjects underwent a battery of neuropsychological tasks that have so far yielded mixed findings in performance differences. Both groups had prolonged reaction times compared with controls in sustained attention tasks; the siblings made more false alarms in the working memory task, but only the patients' performance was poorer in the executive function tasks. These findings further support sustained attention and working memory deficits as potential endophenotypes of schizophrenia. Reaction time and false alarm rates are suggested as additional useful endophenotypic measures that could potentially account for differences in performance in tasks that are not purported to examine the specific measures per se.

Introduction

Schizophrenia is a complex disorder that encompasses several clinical symptom domains and functional impairments. Cognitive deficits are considered core features of the disorder (Bleuler, 1950) and have been established across a wide range of cognitive abilities, recognized as a “generalized deficit” (Bilder et al., 2000). They are already evident at the premorbid stages of the illness (Jones, Rodgers, Murray & Marmot, 1994), in first episode psychosis (Bilder et al., 2000; Braw et al., 2008; Gonzalez-Blanch et al., 2007), they are related to illness outcome and general functionality of the patients (Green, 1996; Keefe, Poe, Walker, & Harvey, 2006) and endure with minimal change after clinical stabilization with pharmacological treatment (Balanza-Martinez et al., 2005; Frangou, Hadjulis, & Vourdas, 2008).

There is increasing evidence for a familial pattern of cognitive deficits in unaffected relatives of schizophrenia patients (seeAllen, Griss, Folley, Hawkins, & Pearlson, 2009; Snitz, MacDonald, & Carter, 2006 ), suggesting that they can serve as putative endophenotypes (i.e., intermediate phenotypes that provide a more reliable index of liability than the illness itself; Gottesman & Shields, 1972) of the disorder. Deficits in sustained attention (Chen et al., 1998; Chen & Faraone, 2000; Lenzenweger, 2001; Maier, Franke, Hain, Kopp, & Rist, 1992; Roitman et al., 1997), working memory (Glahn et al., 2003; Thermenos et al., 2004), and executive function (Birkett et al., 2008; Klemm, Schmidt, Knappe, & Blanz, 2006; Trestman et al., 1995; Voglmaier, Seidman, Salisbury, & McCarley, 1997) have been reported in relatives of schizophrenia patients and subjects with subclinical symptomatology. In general, findings indicate that healthy relatives are impaired, albeit to a lesser degree than patients findings of no impairment have also been reported (Battaglia et al., 1994; Keefe et al., 1994; Laurent et al., 2001; Schreiber et al., 1995; Stratta et al., 1997; Trestman et al., 1995; Zalla et al., 2004).

Based on the criteria for identifying useful endophenotypes summarized by Gottesman and Gould (2003), some measures appear to have more potential than others as a useful endophenotype, with larger effect sizes and more consistent reports of group differences along the schizophrenia spectrum. However, several tasks that are traditionally used to evaluate cognitive processes have so far yielded mixed results (Birkett et al., 2008; Keefe et al., 1994; Klemm et al., 2006; Stratta et al., 1997), thus raising questions regarding the utility of these tasks or different versions of these tasks in schizophrenia research.

In the present study, we explored the familial pattern of cognitive deficits in remitted schizophrenia patients and their unaffected siblings using a battery of neuropsychological tasks assessing sustained attention, executive function, and working memory. The aim of the study was to further clarify the usefulness of these tasks in schizophrenia research as they have yielded mixed findings in performance differences between patients and/or unaffected relatives compared with healthy controls. Moreover, these tasks provide several outcome measures, some of which lack reference in the literature; for example, when assessing working memory, most studies refer to correct responses as the outcome variable, whereas only a few take processing speed into account. Therefore, a second aim of the study was to explore potential differences in “undercited,” but relevant to the schizophrenia substrate, measures of these tasks.

Materials and Methods

Subjects

The study was approved by the Ethics Committee of the University of Crete. Patients with schizophrenia, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; APA, 1994), were recruited through outpatient facilities at the University Hospital of Heraklion, Crete, if they met the following inclusion criteria: (a) 18–50 years; (b) met DSM-IV criteria for remission; (c) were on the same type and dose of medication for the preceding 3 months; and (d) had an unaffected sibling. Exclusion criteria were: (a) additional Axis I or II diagnoses; (b) the presence of a neurological disorder; (c) substance abuse in the preceding 6 months; (d) a positive result on urine toxicology screen at the time of study entry; (e) history of head injury with loss of consciousness. In addition, siblings were excluded if they had a personal history of mood disorder or psychosis. Healthy comparison subjects matched for sex, age, and years of education were also recruited from the local community via advertisement. Additional exclusion criteria for comparison subjects were the presence of personal or family history of mood or schizophrenia spectrum disorders.

Based on the above criteria, 16 schizophrenia patients (12 men and 4 women), 16 unaffected siblings (9 men and 7 women), and 17 healthy comparison subjects (10 men and 7 women) were recruited. All participants underwent the same diagnostic evaluation. The Structured Clinical Interview for DSM-IV Axis I Disorders and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders were used for Axis I and II diagnoses, respectively (First, Spitzer, Gibbon, & Williams et al., 1994; First, Spitzer, Gibbon, & Williams, 1997). Psychopathology was rated using the Brief Psychiatric Rating Scale and the Global Assessment of Functioning. Family history of psychiatric disorders was assessed using the Family Interview for Genetic Studies (Maxwell, 1992), supplemented by medical notes as necessary. Twelve patients were medicated: four were on typical antipsychotics, three were on atypical, and five were on a combination. No patients were on additional medications at the time of the study. After complete description of the study to the subjects, written informed consent was obtained.

The demographic data of the three groups and the clinical characteristics of the patients' group are presented in Table 1. The groups did not differ in age, years of education, sex, and smoking status (all p values of >.09).

Table 1.

Demographic and clinical characteristics (mean [±SD]) of the three groups

 Patients (n= 16) Siblings (n= 16) Controls (n= 17) 
Age (years) 33.31 (6.74) 34.50 (7.67) 31.82 (6.79) 
Education (years) 10.60 (3.08) 10.78 (2.63) 12.82 (3.80) 
Current smokers (%) 81.25 81.25 52.94 
Sex (% male) 75.00 56.25 58.82 
GAF score 61.38 (11.84)   
BPRS score 34.80 (10.50)   
Mean duration of illness (months) 35.38 (30.77)   
Mean antipsychotic dose (CPZ equivalents in mg) 574.42 (499.53)   
Mean antipsychotic dose (clinical equivalents in mg) 284.67 (499.53)   
 Patients (n= 16) Siblings (n= 16) Controls (n= 17) 
Age (years) 33.31 (6.74) 34.50 (7.67) 31.82 (6.79) 
Education (years) 10.60 (3.08) 10.78 (2.63) 12.82 (3.80) 
Current smokers (%) 81.25 81.25 52.94 
Sex (% male) 75.00 56.25 58.82 
GAF score 61.38 (11.84)   
BPRS score 34.80 (10.50)   
Mean duration of illness (months) 35.38 (30.77)   
Mean antipsychotic dose (CPZ equivalents in mg) 574.42 (499.53)   
Mean antipsychotic dose (clinical equivalents in mg) 284.67 (499.53)   

Notes: BPRS = Brief Psychiatric Rating Scale; CPZ = chlorpromazine; GAF = Global Assessment of Functioning.

Neuropsychological Testing

Degraded Continuous Performance Test

Subjects were presented with digits from 0 to 9, degraded to a fixed degree by blurring and superimposing a random pattern of visual noise. The stimuli were presented for 28 ms each at a rate of 1 per second. Participants were instructed to respond as quickly as possible by a button press when the target-digit “0” appeared. The target-digit occurred in a quasi-random fashion in 25% of the 480 trials. The numerals immediately preceding the target were balanced to eliminate sequence recognition. Outcome variables were the number of correct responses, reaction time, A′ (a measure of perceptual sensitivity, referring to an individual's ability to discriminate target from nontarget stimuli) and B′ (a response criterion, measuring the amount of perceptual evidence a person requires to decide that a stimulus is a target).

Span of Apprehension Test

The test consisted of a sequence of upper-case letters randomly assigned in a 4 × 4 matrix on the computer screen, where sets of 3 or 12 letters were flashed for a period of 83 ms on the screen. Each trial contained a “T” or an “E” (the target letters) and 2 or 11 distracter letters, respectively, randomly selected. Subjects were instructed to identify which of the two target letters (T or E) was present among the letters flashed on the screen by pressing one of two buttons (marked with the identified letter). Outcome variables were the number of correct responses and reaction time per condition.

N-Back Sequential Letter Task

The task consisted of four conditions (0-, 1-, 2-, and 3-back) where subjects were asked to respond by a button press when they saw a target letter (letter “X” for 0-back and any letter that was identical to the one presented in the preceding 1, 2, or 3 trials, respectively) on the computer screen. The outcome variables were the percentage of correct responses, the number of false alarms and reaction time.

Stroop Interference Test

The administration and scoring procedures are described in detail elsewhere (Bondi et al., 2002). Briefly here, subjects were asked in three consecutive 45 s periods, first to read the names of colors written in black ink, then to name the color of patterns and, finally, to identify the color of ink that is mismatched to a word (e.g., the word red printed in blue ink is identified as blue). These procedures resulted in a Word (W), a Color (C), and a Color–Word (CW) score. Interference was calculated using the formula CW − CW′, where CW′ is the “predicted number of words”, the subject “could” name in the CW condition, and is derived from (W × C)/(W + C) = CW′.

Wisconsin Card Sorting Test

A computerized version was used. The task consisted of four stimulus cards that varied along three dimensions (color, shape, and number). Participants were asked to match the cards in the deck with one stimulus card and feedback was provided after each selection. Once six consecutive cards were categorized correctly, the sorting principle changed. We used a modified version of the task, as suggested by Nelson (1976) so that the examiner tells the subject when the matching principle changes to reduce the potential distress in a vulnerable population. Outcome variables were the total number of categories achieved, perseverative errors, nonperseverative errors, and total number of errors.

Verbal Fluency

A Greek version (Kosmidis, Vlahou, Panagiotaki, & Kiosseoglou, 2004) of the task was used. On the phonemic fluency subtask, subjects were asked to generate in three consecutive minutes as many as possible words beginning with the letter X (chi), Σ (sigma), and A (alpha) according to the standard instructions. In the semantic fluency subtest, subjects were asked to generate in two consecutive minutes as many as possible words belonging to each of the following semantic categories: animals and fruit. Outcome variables were the number of correct responses per subtask.

Statistical Analyses

The distribution of all variables using the Kolmogorov–Smirnov test was examined and parametric or nonparametric tests were applied, as appropriate. When the reaction time data were not normally distributed, they were transformed using logarithmic transformations (x = log10y), normality of the distribution was again examined and parametric or nonparametric tests were applied, as appropriate. Demographic variables (age, years of education, number of smokers) were compared between the groups using either analysis of variance or Pearson's chi-square. Significant main effects were followed-up with Dunnett's post hoc comparisons or Mann–Whitney tests, as appropriate. All repeated measures with more than two levels (or one degree of freedom) employed the Greenhouse–Geisser ɛ-correction. Uncorrected degrees of freedom are reported in this case, with the corrected p-values and the ɛ-value. Effect sizes (η2) are also reported with values up to 0.01 considered small, up to 0.06 considered medium, and higher than 0.14 considered large effect sizes (Stevens, 2002). To correct for multiple testing and reduce the probability of type I error, the Holm–Bonferroni method (Holm, 1979) was used: starting with the lowest p-value for each set of data, the typical α-value of 0.05 was divided by the total number of significant p-values, to establish the threshold for statistical significance (e.g., 0.05/4 = .0125); if significance was met, the second lowest p-value was compared with 0.05 divided by the number of measures minus 1 (e.g., 0.05/3 = .0167), and so on. This process continued until statistical significance was no longer met.

Results

The mean (±SD) scores for all outcome variables of the neuropsychological tests are presented in Table 2. Group main effects and only the control versus patient and versus sibling contrasts are described below, as the patient versus sibling post hoc analyses were not significant.

Table 2.

Mean (±SD) neuropsychological test performance in the three groups

 Patients Siblings Controls Overall p η2 
Sustained Attention 
 D-CPT      
  Correct responsesa 78.50 (1.71)* 78.13 (2.58)* 78.65 (2.09)* .597 0.02 
  A′a 3.83 (1.81)* 3.83 (1.38)* 3.79 (1.38)* .780 0.01 
  B′a 0.99 (0.00)* 0.99 (0.00)* 0.99 (0.00)* .280 0.05 
  Reaction time (ms) 0.43 (0.04)* 0.41 (0.04)* 0.37 (0.02)b <.001 0.38 
 SOA      
  Correct responses 19.53 (3.82)* 20.16 (4.27)* 23.97 (3.14)b .003 0.23 
  Reaction time (ms) 0.80 (0.11)* 0.75 (0.12)* 0.65 (0.05)b <.001 0.29 
Working Memory 
N-Back      
  Correct responses (%) 74.13 (0.74)* 74.13 (0.78)* 85.87 (0.37)* .090 0.09 
  False alarms 0.66 (0.51)* 0.77 (0.76)* 0.19 (0.18)c .008 0.19 
  Reaction time (ms) 0.71 (0.19)* 0.61 (0.11)* 0.50 (0.10)d .003 0.31 
Executive Function 
 SIT      
  Word score 82.69 (14.97)* 85.38 (13.84)* 99.82 (14.71)b .003 0.23 
  Color score 60.75 (08.91)* 63.13 (11.00)* 72.35 (11.32)b .006 0.19 
  Color–Word score 32.88 (07.54)* 36.69 (10.89)* 46.94 (8.85)b <.001 0.31 
  Interference score −1.96 (07.23)* 0.54 (8.06)* 5.08 (6.52)d .025 0.15 
 WCST      
  Categories achieveda 3.69 (1.89)* 4.81 (1.76)* 5.24 (1.3)d .017 0.17 
  Perseverative errorsa 3.75 (3.02)* 4.19 (5.89)* 2.12 (2.29)* .243 0.06 
  Nonperseverative errors 10.25 (5.14)* 6.19 (3.80)* 4.59 (4.39)d .002 0.23 
  Total errors 17.56 (9.65)* 11.69 (9.33)* 8.00 (8.13)d .014 0.17 
 Verbal Fluency      
  Semantic 19.38 (3.10)* 23.63 (4.13)* 26.29 (7.23)d .002 0.24 
  Phonemic 26.63 (6.91)* 29.00 (9.23)* 34.00 (11.65)* .085 0.10 
 Patients Siblings Controls Overall p η2 
Sustained Attention 
 D-CPT      
  Correct responsesa 78.50 (1.71)* 78.13 (2.58)* 78.65 (2.09)* .597 0.02 
  A′a 3.83 (1.81)* 3.83 (1.38)* 3.79 (1.38)* .780 0.01 
  B′a 0.99 (0.00)* 0.99 (0.00)* 0.99 (0.00)* .280 0.05 
  Reaction time (ms) 0.43 (0.04)* 0.41 (0.04)* 0.37 (0.02)b <.001 0.38 
 SOA      
  Correct responses 19.53 (3.82)* 20.16 (4.27)* 23.97 (3.14)b .003 0.23 
  Reaction time (ms) 0.80 (0.11)* 0.75 (0.12)* 0.65 (0.05)b <.001 0.29 
Working Memory 
N-Back      
  Correct responses (%) 74.13 (0.74)* 74.13 (0.78)* 85.87 (0.37)* .090 0.09 
  False alarms 0.66 (0.51)* 0.77 (0.76)* 0.19 (0.18)c .008 0.19 
  Reaction time (ms) 0.71 (0.19)* 0.61 (0.11)* 0.50 (0.10)d .003 0.31 
Executive Function 
 SIT      
  Word score 82.69 (14.97)* 85.38 (13.84)* 99.82 (14.71)b .003 0.23 
  Color score 60.75 (08.91)* 63.13 (11.00)* 72.35 (11.32)b .006 0.19 
  Color–Word score 32.88 (07.54)* 36.69 (10.89)* 46.94 (8.85)b <.001 0.31 
  Interference score −1.96 (07.23)* 0.54 (8.06)* 5.08 (6.52)d .025 0.15 
 WCST      
  Categories achieveda 3.69 (1.89)* 4.81 (1.76)* 5.24 (1.3)d .017 0.17 
  Perseverative errorsa 3.75 (3.02)* 4.19 (5.89)* 2.12 (2.29)* .243 0.06 
  Nonperseverative errors 10.25 (5.14)* 6.19 (3.80)* 4.59 (4.39)d .002 0.23 
  Total errors 17.56 (9.65)* 11.69 (9.33)* 8.00 (8.13)d .014 0.17 
 Verbal Fluency      
  Semantic 19.38 (3.10)* 23.63 (4.13)* 26.29 (7.23)d .002 0.24 
  Phonemic 26.63 (6.91)* 29.00 (9.23)* 34.00 (11.65)* .085 0.10 

Notes: Means with different superscripts differ at p< .025. D-CPT = Degraded Continuous Performance test; ms = milliseconds; SD = standard deviation; SIT = Stroop Interference test; SOA = span of apprehension test; WCST = Wisconsin Card Sorting test.

aFor this measure, the overall distribution of the score differed from normality and the equivalent nonparametric Kruskal–Wallis test was applied.

bControls differ from patients and siblings.

cControls differ from siblings.

dControls differ from patients.

*No significant differences between groups.

Degraded Continuous Performance Test

Controls presented with shorter reaction times—group main effect: F(2,48) = 13.83, p< .001—compared with both the patients (p < .001) and the siblings (p < .005), but there were not significant differences in correct responses, A′ and B′ scores (all p values >.2).

Span of Apprehension Test

The control group had more correct responses—group main effect: F(2,46) = 6.79, p= .003, η2= 0.228—and shorter reaction time—group main effect: F(2,46) = 9.43, p< .001, η2= 0.291—compared with both the patients (correct responses, p= .003; reaction time, p < .001) and the siblings (correct responses, p= .005; reaction time, p= .006).

N-Back Sequential Letter Task

The control group committed fewer false alarms—group main effect: F(2,46) = 5.38, p= .008, η2= 0.190—compared with the siblings (p = .003) and had shorter reaction time—group main effect: F(2,32) = 7.18, p= .003, η2= 0.310—compared with the patients (p= .001).

Stroop Interference Test

There were significant group main effects in the W, C, and CW scores (all p values <.007) with the control group presenting with higher scores compared with the patients and sibling groups. There were also significant differences in interference—group main effect: F(2,48) = 3.99, p= .025, with the control group performing better compared with the patients (p= .008).

Wisconsin Card Sorting Test

The control group completed successfully more categories (group main effect: Kruskal–Wallis χ2= 8.20, p= .017) compared with the patients (p= .009). They also committed fewer Nelson-type nonperseverative—group main effect: F(2,48) = 6.95, p= .002—and total errors—group main effect: F(2,48) = 4.67, p= .014—compared with the patients (p values <.005).

Verbal Fluency

In semantic verbal fluency, the controls performed better—group main effect: F(2,48) = 7.44, p= .002, η2= 0.244—compared with the patients (p = .001), whereas there were no significant differences in phonemic verbal fluency—F(2,48) = 2.60, p = .085, η2 = 0.101.

Discussion

This study assessed the familial pattern of deficits in sustained attention, working memory, and executive function in remitted-schizophrenia patients and their unaffected siblings. We found that both the patients and their siblings had prolonged reaction times compared with controls in sustained attention tasks and fewer correct responses in the Span of Apprehension Test (SOA) task. The siblings made more false alarms in the working memory task, but only the patients' performance was poorer in the executive function tasks.

Sustained Attention

Deficits in attention have been considered to be “central” to schizophrenia (Braff, 1993) because they contribute to deficits in working memory and executive function. Two widely used measures of sustained attention deficits in schizophrenia have been the Continuous Performance Test (CPT) and SOA tasks. Overall, schizophrenia patients (Chkonia, Roinishvili, Herzog, & Brand, 2010; Kumar et al., 2010), their first-degree relatives (Chen & Faraone, 2000; Snitz et al., 2006), and individuals with subclinical schizophrenia-related symptoms (Chen et al., 1998; Lenzenweger, 2001; Roitman et al., 1997) present with deficient CPT performance. Similarly, schizophrenia patients also typically exhibit reduced performance on the SOA task (Granholm, Asarnow, Verney, Nelson, & Jeste, 1996; Miller, Chapman, Chapman, & Barnett, 1990), although other studies have failed to find a difference between patients and controls (Laurent, Biloa-Tang, et al., 2000; Miller et al., 1990). Relatives of schizophrenia patients (Maier, Franke, Hain, Kopp, & Rist, 1992) as well as healthy individuals scoring high on schizotypal dimensions (Asarnow, Nuechterlein, & Marder, 1983) have exhibited reduced accuracy on the SOA task.

In the present study, deficient performance of both the patient and the sibling groups in terms of correct responses was revealed only in the SOA task. This could be due to differences in the properties of the two tasks, with the easier CPT task leading to ceiling effects in performance. However, the control group presented with better reaction times in both tasks compared with both groups. Reaction time deficits have been observed for decades in the schizophrenia literature (Kietzman & Sutton, 1977; Nuechterlein, 1977) and have traditionally been interpreted as indicative of an attentional dysfunction. The slowing in performance in the siblings group is in accordance with findings with schizotypal subjects (Laurent, d'Amato, et al., 2000; Lenzenweger, 2001) and healthy first-degree relatives of schizophrenia patients (Laurent et al., 2001). Given that these subjects do not have a personal history of psychosis and do not present with a generalized deficit, characteristic of schizophrenia (Bilder et al., 2000), the significantly prolonged reaction time could be related to impairments in the processing speed of incoming information, further supporting the use of this measure as a potential endophenotype of schizophrenia (Krabbendam, Marcelis, Delespaul, Jolles, & van Os, 2001).

Working Memory

A large body of research has demonstrated that patients with schizophrenia have deficits on a varied set of working memory tasks (Lee & Park, 2005) that are associated with impairments in a range of neural mechanisms (Barch, 2005). Further, individuals who share unexpressed genetic components of vulnerability to schizophrenia also experience impairments in working memory function (Glahn et al., 2003; Thermenos et al., 2004). In the present study, we studied working memory defined as temporary online storage and recall of information when manipulation of information is not used in contrast to “executive-functioning working memory,” when information storage, manipulation, and recall of that information are used (Perry et al., 2001). The most widely used working memory task, the n-back task, was employed. In terms of performance differences, there was only a trend for a significant difference in the number of correct responses between the three groups. This is in agreement with other studies, where schizophrenia patients, although scoring lower than controls in the more difficult versions of the n-back task, performed well above the expected performance, indicating adequate engagement in the task (Callicott et al., 2000) and their unaffected siblings were indistinguishable from the healthy comparison subjects (Callicott et al., 2003) in response accuracy. However, controls made fewer false alarms compared with both the patients and the siblings and were faster in responses compared with the patient group only. High false alarm rates in the n-back task have been associated with damage to the prefrontal cortex (Tsuchida & Fellows, 2009), a key-brain region in working memory, and disease-mediated processes in schizophrenia (Eisenberg & Berman, 2010). The present finding of increased false alarm rates in both patients and the siblings suggests that this measure could serve as another useful endophenotype for schizophrenia, apart from the most widely used measure of correct responses.

Executive Function

Executive function deficits have also been widely reported in schizophrenia. A vast amount of research suggests that individuals with schizophrenia experience deficits on the Wisconsin Card Sorting Test (WCST; for review, seeLi, 2004). Research on WSCT performance in first-degree relatives of schizophrenia patients and schizotypal subjects has led to more inconsistent findings. Although several studies have reported reduced WCST performance in first-degree relatives of schizophrenia patients (Birkett et al., 2008; Klemm et al., 2006) and schizotypal subjects (Trestman et al., 1995; Voglmaier, Seidman, Salisbury, & McCarley, 1997), other studies have failed to find this difference (Battaglia et al., 1994; Keefe et al., 1994; Stratta et al., 1997; Zalla et al., 2004). Similarly, deficits in Stroop Interference Test performance have been reported in schizophrenia patients (Frangou, Dakhil, Landau, & Kumari, 2006; Zalla et al., 2004), their unaffected first-degree relatives (Mulet et al., 2007; Zalla et al., 2004), and psychosis-prone healthy individuals (Suhr, 1997), although other studies have reported conflicting results (Laurent et al., 2001; Trestman et al., 1995; Schreiber et al., 1995). A similar pattern in performance exists for verbal fluency, with deficits reported in schizophrenia patients (Bokat & Goldberg, 2003; Bozikas et al., 2010; Henry & Crawford, 2005), their unaffected first-degree relatives (Hughes et al., 2005; Ma et al., 2007), and schizotypal subjects (Barrantes-Vidal et al., 2003).

In the present study, poorer performance in all three executive function tasks was revealed only in the patient group, suggesting that executive function deficits should be viewed with caution, when suggested as endophenotypes for schizophrenia. This finding is in agreement with other studies as well as the low heritability rates of executive function (Wang et al., 2010). However, due to the complexity of executive function processes, the diversity of executive function tasks (many executive tasks are multi-factorial as suggested by Stuss & Alexander, 2000) and schizophrenia, this finding should be viewed with caution. Studies with larger samples, with neurocognitive measures that are highly heritable as well as measures to which a given gene contributes a significant amount of variance should be carried out.

Conclusions

The findings of the present study are in agreement with numerous other studies suggesting that sustained attention and working memory deficits can serve as putative endophenotypes of schizophrenia. The trait nature of these deficits is also supported by the fact that the present study included only Greek participants, therefore arguing against a cultural explanation of the neurocognitive deficits observed in schizophrenia (Davidson & McGlashan, 1997). Additionally, it was revealed that the so far underestimated measures of reaction time and false alarm rates can be useful measures in this respect and could potentially account for differences in performance in tasks that are not purported to examine the specific measures per se. However, the study's limitations include the lack of IQ estimation, which has been reported to affect cognitive task performance; also, the sample size is small, potentially masking significant differences between groups, possibly accounting for the lack of statistically significant differences in critical measures and reducing the generalization of the findings. Therefore, larger scale studies are needed in order to further clarify the nature and the stability of the deficits.

Conflict of Interest

None declared.

Acknowledgements

PR was supported by a “Manasaki Foundation” scholarship. The authors have no conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of the manuscript, to disclose.

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