Elsevier

Psychiatry Research

Volume 168, Issue 2, 30 July 2009, Pages 102-109
Psychiatry Research

Attention network test (ANT) reveals gender-specific alterations of executive function in schizophrenia

https://doi.org/10.1016/j.psychres.2008.04.006Get rights and content

Abstract

The Attention Network Test (ANT) provides measures for three different components of visual attention: executive control (= conflict inhibition), orienting, and alerting. There is reasonable evidence that alterations of attention—mainly in the executive/conflict domain—are associated with susceptibility to psychiatric illness. Specific impairments may be a characteristic for a medical condition such as schizophrenia and thus shift our understanding from a neuropsychological endophenotype to a more precise genetic understanding of this disorder. Study subjects comprised 35 schizophrenic patients and 35 healthy controls (13 female and 22 male in both groups). The ANT was administered to all participants and rated individual responses for the three factors (alerting, orienting, and conflict) and their respective ratios relative to mean reaction times. With regard to gender differences, group comparisons were performed for schizophrenic patients vs. healthy controls. Significant differences between patients and controls could be detected for mean reaction time (639 vs. 538 ms) and for conflict ratio (0.158 vs. 0.191). The latter difference mainly resulted from gender-specific variances of the conflict network in opposite directions. The executive function as represented by the conflict network of visual attention of the ANT is affected in schizophrenia. We have detected hitherto unreported gender-specific differences between healthy controls and schizophrenic patients. Especially as regards the conflict network, the ANT offers a promising methodology to detect a neuropsychological endophenotype of schizophrenia.

Introduction

Visual attention may be regarded as an integrated brain function combining three different specialised networks: the alerting network, the orienting network, and the executive control network (Posner and Petersen, 1990). The alerting network can effectuate a wakeful state to prepare for sensory input. The orienting network can focus attention on relevant sources of expected sensory input. The executive network (= conflict network) is involved in complex decision making and error monitoring.

The Attention Network Test (ANT) is a neurocognitive test that was developed to provide a separate measure for these three different components of visual attention. Validation data in a healthy population showed sufficient independence of the three networks and generated reliable single-subject estimates of alerting, orienting, and executive function (Fan et al., 2002). A twin study yielded evidence for heritability of the measured variables, with the exception of the orienting effect (Fan et al., 2001). With an adapted version of the ANT, the development of attentional networks during childhood was investigated (Rueda et al., 2004), indicating that reaction time, alerting, and accuracy improved with age, executive function remained stable after the age of seven, and orienting was not influenced by age. In healthy adults activation patterns in neuroimaging studies showed specific anatomical locations of the three networks in the human brain (Fan et al., 2005, Kincade et al., 2005, Thiel et al., 2004). Genetic studies revealed associations of polymorphisms in candidate genes for psychiatric diseases (dopamine D4 receptor (DRD4), dopamine transporter (DAT), catechol-O-methyl transferase (COMT), monoamine oxidase A (MAOA) and tryptophan hydroxylase 2 (TPH2)) with visual attention, and activation in the anterior cingulate cortex (ACC) (Fan et al., 2003, Fossella et al., 2002, Opgen-Rhein et al., 2008, Reuter et al., 2007). Wang et al. (2005) administered the ANT to a group of Chinese schizophrenic patients and healthy controls, demonstrating large and highly significant differences in the executive network and smaller but significant differences in the orienting network. Gooding et al. (2006) confirmed these findings, showing that schizophrenia-spectrum patients take longer on average to resolve conflict. Our group found lower ACC activity during resolution of conflict in schizophrenic patients (Neuhaus et al., 2007), and Nestor et al. (2007) found differences in the alerting and in the orienting network. Moreover, other neurocognitive tasks, also measuring reaction time as a function of stimulus conflict in schizophrenia-spectrum patients, contributed substantially to this field of research recently (Guillaume et al., 2007, Steel et al., 2007).

Schizophrenia today is mainly viewed as a neurodevelopmental disorder (Cannon et al., 1999, Lewis and Levitt, 2002), leading to subsequent alterations of brain morphology (Andreasen et al., 1990, Antonova et al., 2005, Cannon and Marco, 1994) and function (Aleman et al., 1999, Barch et al., 2001, Caspi et al., 2003). Defective neuronal development is likely to be evoked by complex polygenetic constellations, and some promising candidate genes increasing susceptibility for schizophrenia have been found (Harrison and Weinberger, 2005). Therefore a different perspective on the disorder has been proposed: to define the phenotype on the basis of abnormalities in neural circuits and in fundamental cognitive processes (Andreasen, 2000). Pursuing the plan to identify such a phenotype, the detection of a well-defined neuropsychological endophenotype could amalgamate genetic susceptibility and cognitive impairments (Cornblatt and Malhotra, 2001, Gottesman and Gould, 2003). By applying the ANT to schizophrenia patients we aimed at detecting specific alterations that might serve as a potential endophenotype for schizophrenia. We expected to find differences mainly in the executive network, as alterations in this domain have been described in schizophrenia consistently (Heinrichs and Zakzanis, 1998, Hutton et al., 1998, Wolf et al., 2002). Moreover, we wanted to look for possible influencing factors for the expected performance variations. Taking into account that a recent study of a large population-based sample indicated a substantial influence of gender and free testosterone on cognitive performance (Thilers et al., 2006), and that many researchers reported—albeit often ambiguous—influences of gender on cognitive performance (Hoff and Kremen, 2002), we planned to examine gender differences in our sample.

Section snippets

Subjects

Thirty-five Caucasian schizophrenic inpatients (13 female, 22 male) participated in this study. Two trained psychiatrists confirmed their diagnoses by the Structured Clinical Interviews for DSM-IV-TR Axis I Disorders (First et al., 2002) and for DSM-IV Personality Disorders (First et al., 1997) independently, and rated patients on the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987). Patients neither had other axis I (including substance abuse other than smoking tobacco) or axis

Subject characteristics

Healthy controls (3 left-handed, 30 right-handed and 2 ambidextrous) had a mean age of 34.3 years [21–61], a mean education time of 14.2 years [10–19] and had consumed a mean of 8.0 pack years of cigarettes [0–70]. The schizophrenia sample included patients with the paranoid subtype (N = 30; 86%), with the remaining patients diagnosed with the disorganised (N = 3) or undifferentiated (N = 2) subtype. Schizophrenic patients (6 left-handed, 27 right-handed and 2 ambidextrous) had a mean age of

Discussion

Our results indicate that the ANT is a suitable neurocognitive test to measure different aspects of attention in a clinical population of schizophrenic patients. The significantly longer mean RTs of schizophrenic patients may reflect a global impairment of attention as reported in many previous investigations (Aleman et al., 1999, Allen et al., 2003, Erlenmeyer-Kimling and Cornblatt, 1992). Regarding the three attentional networks, only the conflict ratio differed significantly between patients

Acknowledgements

The authors thank André Conrad and Matthew Rubenstein for their comments and editorial assistance.

References (61)

  • KremenW.S. et al.

    Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands

    Psychiatry Research

    (1997)
  • MaruffP. et al.

    Asymmetries in the covert orienting of visual spatial attention in schizophrenia

    Neuropsychologia

    (1995)
  • NestorP.G. et al.

    Attentional networks and cingulum bundle in chronic schizophrenia

    Schizophrenia Research

    (2007)
  • NeuhausA.H. et al.

    Selective anterior cingulate cortex deficit during conflict solution in schizophrenia: an event-related potential study

    Journal of Psychiatric Research

    (2007)
  • RuedaM.R. et al.

    Development of attentional networks in childhood

    Neuropsychologia

    (2004)
  • SeidmanL.J. et al.

    Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability

    Biological Psychiatry

    (1997)
  • SteelC. et al.

    Associations between schizotypal personality traits and the facilitation and inhibition of the speed of contextually cued responses

    Psychiatry Research

    (2007)
  • ThielC.M. et al.

    Cerebral correlates of alerting, orienting and reorienting of visuospatial attention: an event-related fMRI study

    NeuroImage

    (2004)
  • ThilersP.P. et al.

    The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-oldmen and women

    Psychoneuroendocrinology

    (2006)
  • WangK. et al.

    Selective impairment of attentional networks of orienting and executive control in schizophrenia

    Schizophrenia Research

    (2005)
  • WigalS.B. et al.

    Lateralized attentional deficits in drug-free and medicated schizophrenic patients

    Neuropsychologia

    (1997)
  • WolfL.E. et al.

    Wisconsin Card Sorting deficits in the offspring of schizophrenics in the New York High-Risk Project

    Schizophrenia Research

    (2002)
  • AlemanA. et al.

    Memory impairment in schizophrenia: a meta-analysis

    American Journal of Psychiatry

    (1999)
  • AllenD.N. et al.

    A consideration of neuropsychologically normal schizophrenia

    Journal of the International Neuropsychological Society

    (2003)
  • AndreasenN.C. et al.

    Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities

    Archives of General Psychiatry

    (1990)
  • BarchD.M. et al.

    Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia

    Archives of General Psychiatry

    (2001)
  • CannonT.D. et al.

    Structural brain abnormalities as indicators of vulnerability to schizophrenia

    Schizophrenia Bulletin

    (1994)
  • CannonT.D. et al.

    A prospective cohort study of neurodevelopmental processes in the genesis and epigenesis of schizophrenia

    Development and Psychopathology

    (1999)
  • CannonT.D. et al.

    Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers

    Archives of General Psychiatry

    (1994)
  • CornblattB.A. et al.

    Impaired attention as an endophenotype for molecular genetic studies of schizophrenia

    American Journal of Medical Genetics

    (2001)
  • Cited by (34)

    • A systematic review comparing sex differences in cognitive function in schizophrenia and in rodent models for schizophrenia, implications for improved therapeutic strategies

      2016, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Deficits in attention (Goldstein et al., 1998; Zhang et al., 2012a), verbal memory (Goldstein et al., 1998; Vaskinn et al., 2011), cognitive flexibility (Vaskinn et al., 2011), language, executive function (Goldstein et al., 1998), mental rotation performances (Jimenez et al., 2009), working memory (Malaspina et al., 2012b), immediate and delayed memory and RBANS total score (Zhang et al., 2012a) were also observed specifically in male SP groups but not in female SP or HC groups. It is important to note that, despite the large number of studies demonstrating sexual dimorphism in cognitive function in schizophrenia, several studies have shown no difference between the performance of men and women in FE and SP groups, or in HC groups (Halari et al., 2004; Kao et al., 2013; Karilampi et al., 2011; Moriarity et al., 2001; Urbanek et al., 2009) (see Table 1c for details of these studies). When comparing male and female SP groups for symptom profiles, most of the studies reported more severe negative symptoms in males (Moriarity et al., 2001; Ramos-Loyo et al., 2012; Torniainen et al., 2011; Zhang et al., 2012a) while more severe positive symptoms in males have been observed by others (Roesch-Ely et al., 2009).

    View all citing articles on Scopus
    View full text