Attention deficits belong to the most prominent impairments among a wide range of cognitive deficits in schizophrenia patients . In recent theories the concept of attention has been divided into three subdomains including "alerting", "orienting" and "executive control" [2, 3]. Alerting comprises the cognitive control of wakefulness and arousal (intrinsic alertness) and the ability to increase response readiness for a short period of time subsequent to external cues (phasic alertness) . Orienting refers to the overt or covert directing of spatial attention to unattended stimuli. Executive control of attention requires the ability to respond to one aspect of a stimulus while ignoring another (more dominant) aspect. In schizophrenia, deficits have been demonstrated in each of these three attentional subdomains [5–8]. To a lesser extent, impaired attention can also be found in non-psychotic relatives of schizophrenia patients. Accordingly, attention deficits might index genetic liability [9–13].
Investigating the neural correlates of attention deficits in schizophrenia patients and groups at genetic risk compared to healthy subjects might elucidate the mechanisms how genes can lead to the manifestation of a cognitive deficit. In healthy subjects, functional imaging studies have shown distinct neural networks underlying each of the three above mentioned attentional domains. Alerting has been shown to rely on thalamic, prefrontal and parietal areas [4, 14–16]. Orienting has been associated with activation of the superior parietal lobe, temporal parietal junction, and frontal eye fields [14, 17–19]. Executive control of attention has been consistently related to activation of the anterior cingulate and lateral prefrontal cortex [14, 20–23]. While networks of alerting and orienting are lateralized to the right hemisphere [3, 4, 18], executive control shows a left lateral prefrontal bias [23, 24].
Functional imaging studies have revealed dysfunctions of these networks in schizophrenia patients associated with the performance of attentional tasks requiring alerting, orienting or executive control [25–27]. Likewise, in relatives of schizophrenia patients, alterations have been found in networks of various cognitive domains  and in particular of the attention systems [29–31]. Neural abnormalities in relatives were similar to those in schizophrenia patients, and it was suggested that reduced BOLD activity in attention networks may be an intermediate marker for schizophrenia .
The studies in relatives have shown that genetic liability in general affects neural correlates of attention. However, schizophrenia has a polygenetic pattern of heredity and the impact of single genes on neural networks of cognition is largely unknown. Fan et al.  found that polymorphisms in dopamine receptor (DRD4) and monoamine oxidase A (MAOA) genes led to impaired executive control of attention in healthy subjects and that this was associated with reduced neural activity of the anterior cingulate cortex. The effect of (other) single gene variants on neural networks in healthy subjects has recently also been shown for other cognitive domains [33–41].
Several susceptibility genes for schizophrenia have been detected in recent years, including DTNBP1, neuregulin 1 (NRG1), catechol-O-methyltransferase (COMT), disrupted-in-schizophrenia 1 (DISC1), regulator of G-protein signalling 4 (RGS4), G72, proline dehydrogenase (PRODH), and D-amino acid oxidase (DAAO) [42–44]. Among these, DTNBP1 stands out as one of the best replicated susceptibility genes [45, 46]. It has been shown to affect personality traits [47, 48], intelligence [49–53], attention capacity , verbal fluency [37, 52] and several memory domains [52–55] in both healthy subjects and patients with schizophrenia. In particular, negative symptoms in schizophrenia have been shown to be associated with several SNP of the DTNBP1 gene [56, 57].
The effect of DTNBP1 on cognitive functions has been supposed to be mediated by the glutamate neurotransmitter system, acting via the prefrontal cortex . In a gene expression study, Weickert et al.  showed that DTNBP1 mRNA levels varied depending on the DTNBP1 genotype and that schizophrenia patients showed significantly reduced DTNBP1 mRNA levels in the dorsolateral prefrontal cortex. Several SNPs of DTNBP1 have been detected and discussed as risk factors for schizophrenia . In particular, the minor T allele of the SNP rs1018381 (P1578) which has a frequency of about 9% in the Caucasian population  can be regarded as an important risk factor. It has been shown to be strongly associated with schizophrenia in two of three independent samples of different ethnic origin (white and Hispanic, but not African American; . In a study by Burdick et al. , this SNP was also the only one that showed a significant effect on general cognitive ability in patients and controls. Finally, a recent study on healthy individuals by Luciano et al.  provided further evidence for an association between the rs1018381 minor T allele and cognitive deficits in an Australian and Scottish cohort and a trend for an association was found for the English cohort.
The aim of the present study was to investigate the effects of SNP rs1018381 of the DTNBP1
gene on neural attention networks of alerting, orienting and executive control in healthy subjects. As an activation paradigm we used a modified version of the attention network test (ANT) developed by Fan et al. [63
]. This test is capable of probing the three attention networks in one single reaction time task. Gene effects were expected to occur in brain areas known to be involved in alerting, orienting or executive control and to be impaired in schizophrenia patients. We hypothesized that risk allele carriers show reduced neural activity in
prefrontal and parietal areas (with a right hemisphere bias) associated with alerting.
superior parietal areas and the temporal parietal junction (with a right hemisphere bias) associated with orienting.
anterior cingulate cortex and lateral prefrontal areas (with a left hemisphere bias) associated with executive control of attention.