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Background: An adaptive neural stress response is essential to adequately cope with a changing environment. It was previously argued that sympathetic/noradrenergic activity during acute stress increases salience network (SN) connectivity and reduces executive control network (ECN) connectivity in healthy controls, with opposing effects in the late aftermath of stress. Altered temporal dynamics of these networks in response to stress are thought to play a role in the development of psychopathology in vulnerable individuals., Methods: We exposed male healthy controls (n = 40, mean age = 33.9) and unaffected siblings of schizophrenia patients (n = 39, mean age = 33.2) to the stress or control condition of the trier social stress test and subsequently investigated resting state functional connectivity of the SN and ECN directly after and 1.5 h after stress., Results: Acute stress resulted in increased functional connectivity within the SN in healthy controls, but not in siblings (group × stress interaction pfwe < 0.05). In the late aftermath of stress, stress reduced functional connectivity within the SN in both groups. Moreover, we found increased functional connectivity between the ECN and the cerebellum in the aftermath of stress in both healthy controls and siblings of schizophrenia patients., Conclusions: The results show profound differences between siblings of schizophrenia patients and controls during acute stress. Siblings lacked the upregulation of neural resources necessary to quickly and adequately cope with a stressor. This points to a reduced dynamic range in the sympathetic response, and may constitute a vulnerability factor for the development of psychopathology in this at-risk group.

Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute stress is known to affect the way we process rewards. For example, during, or directly after stress, activity within key brain areas of the reward circuitry is reduced when a reward is presented. Generally, the effects of stress on the brain are time-dependent, changing neural and cognitive processing in the aftermath of stress to aid recovery. Such a dynamic response to stress is important for resilience on the longer term. However, relatively little is known about reward processing during the recovery phase of stress and whether this is changed in individuals at increased risk for stress-related psychopathology. Healthy male individuals (N = 40) and unaffected siblings of schizophrenia patients (N = 40) were randomized to either an acute stress task (Trier Social Stress Test) or a no-stress task. Neural responses during reward anticipation and reward feedback (monetary gain or no gain) were examined 50 min later using an fMRI monetary incentive delay task. The ventral striatum and orbitofrontal cortex (OFC) were used as predefined hypothesis-driven regions of interest. Neural responses following stress differed between controls and siblings during reward feedback (group × stress interaction OFC p = 0.003, ventral striatum p = 0.031), showing increased ventral striatum and OFC responses following stress in healthy controls only. Exploratory analyses revealed that this effect was most pronounced during hit trials (compared to when a reward was omitted), and independent of monetary value. Stress did not affect subsequent reward processing in siblings of schizophrenia patients. We found no significant differences between controls and siblings in ventral striatum and OFC responses during reward anticipation following stress. This study shows that ventral striatum and OFC responses to positive task feedback are increased in the aftermath of stress in healthy male controls, regardless of monetary value. This indicates a dynamic shift from previously reported reduced responses in the striatum and OFC to reward feedback directly after stress to increased responses to both reward and non-reward feedback during the recovery phase of stress. These increased neural responses following stress were absent in siblings of schizophrenia patients. Together, these findings indicate that stress recovery is affected in this at-risk group, particularly in responses to positive feedback following stress., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: Misattribution of symptoms is a common feature of schizophrenia, and likely involves impairment of metacognitive function that may be mediated by the frontal cortex. We aimed to compare frontal cortical thickness in first-episode schizophrenia (FES) patients with matched controls, and investigate its relationship with the symptom attribution dimension of insight in FES patients., Methods: We examined frontal cortical thickness in 92 minimally treated FES patients at baseline presentation and 93 healthy controls aged 16-45 years. We examined for correlations between symptom attribution as determined by the Birchwood Insight Scale (BIS) symptom relabeling subscale score and cortical thickness of frontal regions of interest (ROIs). We then examined for an association between symptom attribution and cortical thickness using multiple regression analysis., Results: FES patients exhibited significantly reduced cortical thicknesses for a number of frontal regions, namely the left medial orbitofrontal, left superior frontal, left frontal pole, right rostral middle frontal, right lateral orbitofrontal and right superior frontal regions. Reduced cortical thickness in FES patients was associated with symptom misattribution for the left and right rostral middle frontal, left caudal anterior cingulate, right superior frontal, and left and right pars triangularis regions. Reduced left rostral middle frontal thickness and left anterior cingulate thickness remained significant on regression analysis., Conclusion: Our findings suggest that frontal neuroanatomical deficits that are present early in the disease process may be critical to the pathogenesis of symptom attribution in schizophrenia., (© 2016 John Wiley & Sons Australia, Ltd.)

Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity., (Copyright © 2016. Published by Elsevier B.V.)

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n= 21) and noncarriers (n= 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

People generally experience themselves as the cause of outcomes following from their own actions. Such agency inferences occur fluently and are essential to social interaction. However, schizophrenia patients often experience difficulties in distinguishing their own actions from those of others. Building on recent research into the neural substrates underlying agency inferences in healthy individuals, the present study investigates how these inferences are represented on a neural level in patients with schizophrenia. Thirty-one schizophrenia patients and 31 healthy controls performed an agency inference task while functional magnetic resonance images were obtained. Participants were presented with a task wherein the relationship between their actions and the subsequent outcomes was ambiguous. They received instructions to cause specific outcomes to occur by pressing a key, but the task was designed to match or mismatch the color outcome with the participants' goal. Both groups experienced stronger agency when their goal matched (vs. mismatched) the outcome. However, region of interest analyses revealed that only controls showed the expected involvement of the medial prefrontal cortex and superior frontal gyrus, whereas in patients the agency experience was not related to brain activation. These findings are discussed in light of a hypofrontality model of schizophrenia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Schizophrenia is a severe psychiatric disorder associated with impaired fronto-striatal functioning. Similar deficits are observed in unaffected siblings of patients, indicating that these deficits are linked to a familial risk for the disorder. Fronto-striatal deficits may arise during adolescence and precede clinical manifestation of the disorder. However, the development of the fronto-striatal network in adolescents at increased familial risk for schizophrenia is still poorly understood. In this cross-sectional study, we investigate the impact of familial risk on fronto-striatal functioning across age related to reward anticipation and receipt in 25 adolescent offspring of schizophrenia patients (SZ offspring) and 36 age-matched healthy controls (range 10-19years). Subjects performed a reward task while being scanned with functional MRI. Overall response times and the amount of money won did not differ between the groups. Striatal activation during reward anticipation decreased across age in the SZ offspring, while it did not in the healthy controls. Activation in the orbitofrontal cortex during reward receipt did not differ between the groups. These results, taken together with data from adult schizophrenia patients and their siblings, indicate that the diminishing striatal activation across adolescence may signify a familial vulnerability for schizophrenia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Studies of pre-and post-treatment striatal volume in schizophrenia have reported conflicting results., Materials and Methods: We assessed dorsal striatal (caudate and putamen) volumes bilaterally in 22 never-treated, non-substance-abusing patients with first-episode schizophrenia or schizophreniform disorder and 23 healthy controls matched for age, sex and educational status. Patients received either risperidone or flupenthixol long acting injection and were compared by structural MRI with controls at weeks 0, 4 and 13. T1-weighted data on a 3T MRI scanner were obtained and images were reconstructed using FreeSurfer. Treatment outcome was assessed by changes in psychopathology, insight, functionality, cognitive performance and motor symptoms., Results: Caudate, but not putamen volumes was significantly larger in patients bilaterally at baseline (P=0.01). Linear mixed effects repeated measures found no significant group × time interactions for any of the regions. Caudate volume was not significantly associated with improvements in psychotic symptoms. Also, the findings of a regression model were inconsistent insofar as larger caudate volume was associated with less improvement in depression scores, greater improvement in functionality and greater improvement in verbal learning but less improvement in reasoning and problem solving (left caudate) and composite cognitive score (right caudate)., Conclusions: The increased caudate volumes prior to treatment are contrary to previous reports in never-treated patients with first-episode schizophrenia, and together with our failure to demonstrate volume changes related to acute treatment, call into question previous proposals that enlarged caudate volume is a consequence of antipsychotic treatment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Schizophrenia is a psychiatric disorder that is associated with impaired functioning of the fronto-striatal network, in particular during reward processing. However, it is unclear whether this dysfunction is related to the illness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward processing in unaffected siblings of schizophrenia patients using functional magnetic resonance imaging. Brain activity was measured during reward anticipation and reward outcome in 27 unaffected siblings of schizophrenia patients and 29 healthy volunteers using a modified monetary incentive delay task. Task performance was manipulated online so that all subjects won the same amount of money. Despite equal performance, siblings showed reduced activation in the ventral striatum, insula, and supplementary motor area (SMA) during reward anticipation compared to controls. Decreased ventral striatal activation in siblings was correlated with sub-clinical negative symptoms. During the outcome of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to controls. Our finding of decreased activity in the ventral striatum during reward anticipation and increased activity in this region during receiving reward may indicate impaired cue processing in siblings. This is consistent with the notion of dopamine dysfunction typically associated with schizophrenia. Since unaffected siblings share on average 50% of their genes with their ill relatives, these deficits may be related to the genetic vulnerability for schizophrenia., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Impaired working memory (WM) is a hallmark of schizophrenia. In addition to classical WM regions such as the dorsolateral prefrontal cortex (DLPFC) and the striatum, dysfunctions in the default-mode network (DMN) contribute to these WM deficits. Unaffected siblings of patients also show WM impairments. However, the nature of the functional deficits underlying these impairments is unclear, mainly because of impaired performance confounding neuroimaging results., Methods: Here, we investigated WM and DMN activity in 23 unaffected siblings of schizophrenia patients and 24 healthy volunteers using fMRI and a Sternberg WM task. WM load was determined prior to scanning to ensure 90% accuracy for all subjects., Results: Siblings showed hyperactivation during the encoding phase of WM in the right medial prefrontal cortex (MPFC) which is the anterior part of the DMN. No differences were found during the maintenance phase. During the retrieval phase, siblings showed hyperactivation in WM regions: DLPFC, inferior parietal cortex and the striatum. Siblings who showed hyperactivity in the MPFC during encoding showed DLPFC and striatum hyperactivation during retrieval., Conclusions: Our finding of hyperactivation in WM and DMN areas indicates that siblings fail to adequately inhibit DMN activity during demanding cognitive tasks and subsequently hyperactivate WM areas. This failure may reflect dopamine hyperactivity in the striatum which prevents adequate DMN suppression needed for effective WM. This study provides support for the notion that aberrant WM and DMN activation patterns may represent candidate endophenotypes for schizophrenia., (© 2013 Elsevier B.V. All rights reserved.)

The default-mode network (DMN) of the brain shows highly coherent intrinsic activity in healthy subjects and is implicated in self-referential processing important for social cognitive functioning. Schizophrenia patients show abnormal resting-state connectivity within the DMN and this aberrant connectivity is thought to contribute to difficulties in self-referential and introspective processing. Subjects at increased genetic risk of developing schizophrenia, including unaffected siblings of patients, also exhibit brain abnormalities and impaired social cognitive processing. However, it is unclear whether resting-state connectivity within the DMN is abnormal in these subjects. Here, we investigate resting-state DMN connectivity in siblings and whether this is related to the functioning of the network during self-referential processing. Brain activity was measured using functional MRI in 25 unaffected siblings of patients with schizophrenia and 25 healthy controls during an 8-minute resting-state period and during a self-referential processing task in which the subjects had to indicate whether a trait adjective (e.g. "lazy") described their personality (self-referential condition) or whether the trait was socially desirable (non-referential condition). Compared with controls, siblings showed exaggerated connectivity during resting-state between the midline areas of the DMN. Moreover, they failed to adequately modulate connectivity between these areas during self-referential processing. No abnormalities in activation during self-referential processing were observed. These findings suggest that subjects at increased genetic risk of developing schizophrenia exhibit abnormal intrinsic connectivity within the midline DMN and that this is associated with aberrant interactions between these regions during self-referential processing., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Inhibitory control is central to executive functioning and appears deficient in schizophrenia. However, it is unclear how inhibitory control is affected, what the underlying neural mechanisms are, whether these deficits are related to the illness itself or to increased risk for the illness, and whether there is a relation to impairments in other executive functions., Methods: We used functional magnetic resonance imaging to investigate two forms of inhibitory control: proactive inhibition (anticipation of stopping) and reactive inhibition (outright stopping). Twenty-four schizophrenia patients, 24 unaffected siblings, and 24 healthy control subjects performed a modified version of the stop-signal paradigm. To assess the relation between performance on inhibitory control and other executive functions, we correlated inhibitory control indices with working memory span., Results: Compared with control subjects, proactive inhibition was reduced in patients and siblings. Reactive inhibition was unaffected. Reduced proactive inhibition was associated with a failure to activate the right striatum, the right inferior frontal cortex, and the left and right temporoparietal junction. Activation during reactive inhibition was unaffected. Those patients with the least proactive inhibition also showed the shortest working memory span., Conclusions: These results suggest that schizophrenia is associated with reduced proactive inhibition, probably resulting from corticostriatal dysfunction. This deficit is related to an increased risk for schizophrenia and likely reflects a general executive function deficit rather than a specific inhibitory control impairment., (2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Dysfunction of the frontal lobe is considered to be central to the pathology of schizophrenia. However, the nature of these abnormalities is unclear, in particular whether they are affected by treatment. In an earlier functional MRI study of our group we found dorsolateral prefrontal lobe (DLPFC) dysfunction to be present in medication-naive first-episode patients. In this follow-up study, we investigated whether treatment with atypical antipsychotics had an effect on DLPFC functioning, and whether (change in) DLPFC functioning was related to treatment response. Twenty-three medication-naive, first-episode male schizophrenia patients and 33 matched healthy controls were scanned at baseline and were re-scanned after 10 weeks, while performing a modified Sternberg working-memory task. We specifically investigated the effect of practice on brain activation, defined as the signal change between a novel and practiced working-memory task. After the baseline scan, patients were treated with atypical antipsychotics. Based on their symptom change after ten weeks, patients were divided into responders and non-responders We found DLPFC function did not change after 10 weeks in healthy controls or in patients who received treatment. However, while patients who responded to treatment did not differ from controls, non-responders showed a reduced practice effect in the DLPFC that was present already at baseline, which did not change after treatment. A reduced practice effect in the DLFPC at baseline was found to be predictive of poor treatment response at 10 weeks. These results suggest that prefrontal lobe dysfunction reflects a distinct neuropathological substrate in a subgroup of treatment non-responsive schizophrenia patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Schizophrenia is characterized by impaired social cognition, including emotion processing. Behavioral studies have reported impaired performance on various emotion processing tasks, and imaging studies in patients have observed aberrant activity within the underlying neural circuitry. Also, subjects at increased genetic risk of developing schizophrenia, including unaffected siblings of patients, show behavioral impairments in emotion processing. It is unclear, however, whether and how the underlying neural system is disrupted in these subjects. In this study, we investigated whether siblings of patients with schizophrenia show abnormal brain activation during basic emotion processing., Methods: Brain activity was measured using functional magnetic resonance imaging in 24 unaffected siblings of patients with schizophrenia and 25 healthy control subjects while they viewed and rated neutral, positive, and negative pictures. None of the subjects had a psychiatric disorder, and the two groups did not differ in age, gender, or level of own, paternal, or maternal education., Results: Compared with control subjects, siblings showed increased activity within the amygdala, hippocampus, medial prefrontal cortex, posterior and anterior cingulate cortex, and middle temporal gyrus in response to emotionally arousing pictures relative to neutral pictures. No activation differences between the groups were found during the neutral stimuli, indicating that the observed hyperactivity is likely caused by abnormal emotion processing rather than impaired visuoattentional processing., Conclusions: Our findings of hyperactivity in siblings during emotion processing suggest that functional abnormalities within the neural circuitry of emotion processing are related to the genetic risk for developing schizophrenia., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Abnormalities in the frontal lobe are considered to be central to the pathology of schizophrenia. Neuroimaging studies indeed report abnormal function of the frontal lobe in schizophrenia patients. However, the nature of these functional abnormalities is unclear, in particular whether they are affected by medication. We therefore investigated whether frontal functioning is already abnormal in first-episode medication-naive schizophrenia, and if so, if this dysfunction is related to symptomatology. Thirty medication-naive male patients with first-episode schizophrenia and 36 matched healthy controls performed a modified working memory task while fMRI data were acquired. During the task, subjects were presented with novel task (NT) and practiced task (PT) memory sets. Compared to controls, patients showed reduced performance during NT and PT. However, both groups performed better during PT, indicating that practice improved performance. Importantly, practice reduced brain activation in both patients and controls, but this effect of practice was significantly smaller in patients compared to controls, specifically in the left dorsolateral prefrontal cortex (DLPFC; p=0.01). The reduced effect of practice on brain activation was related to the severity of negative symptoms and disorganization. These results suggest that DLPFC function is deficient in the early phases of schizophrenia and cannot be attributed to the use of antipsychotics., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Schizophrenia has been frequently associated with impaired inhibitory control. Such control is known to involve the striatum. Here, we investigate whether impaired inhibitory control is associated with abnormal striatal activation in schizophrenia. First-degree relatives of patients were also tested to examine whether striatal abnormality is associated with schizophrenia, or with the risk for the illness., Methods: Both functional MRI and behavioral data were acquired during a task designed to invoke inhibitory control in 21 patients, 15 unaffected siblings, and 36 matched controls. Subjects must refrain from responding to designated stop cues occurring within a series of motor cues. Subjects could anticipate the occurrence of stop cues as the likelihood of these cues increased in a linear fashion throughout the task., Results: Control subjects showed striatal activation while responding to motor cues. This activation increased in a linear fashion when the likelihood of having to inhibit the response was increased. Both patients siblings did not show anticipation-related increase in either striatal activation. However, only patients showed behavioral impairments., Conclusions: Striatal abnormalities occur in schizophrenia patients and unaffected siblings. Thus striatal abnormalities may be related to an increased (genetic) risk to develop schizophrenia.

Background: Schizophrenia patients have difficulty inhibiting automatic saccades. Many studies have failed to resolve whether healthy first-degree relatives share the same deficit. Measures of brain activity may be more sensitive than behavioral measures. In patients, the saccadic inhibition deficit has been related to impaired frontostriatal functioning. This study attempts to establish whether this abnormality is also present in unaffected relatives of patients., Methods: Functional brain images were acquired during prosaccades and antisaccades in 16 control subjects and 16 unaffected siblings of schizophrenia patients using an event-related functional magnetic resonance imaging design. Eye movements were measured during scanning., Results: The task activated a network of regions corresponding to the oculomotor system. Siblings and control subjects did not differ during execution of prosaccades. During antisaccades, siblings did not activate the caudate nucleus. Siblings and control subjects did not differ on the percentage of antisaccade errors., Conclusions: Siblings did not appropriately activate the striatum during antisaccades, similar to what has been reported in patients. Siblings, however, did not make significantly more errors during antisaccades, indicating that they were able to compensate for the inactive caudate. Future research is needed to assess the potential of this striatal deficit as (genetic) risk factor for schizophrenia.

Reduced spatial negative priming (SNP) in schizophrenia is commonly attributed to the inability to filter out irrelevant information. However, some investigators have suggested that reduced SNP in patients is caused by either perceptual mismatching or salience of the distracter. The goal of the present study was to determine the influence of these perceptual processes. In this preliminary report, we present data of 15 schizophrenia patients on atypical medication and 15 matched healthy controls. Compared to controls, patients showed a reduced SNP effect, even when controlled for perceptual mismatching. This reduced effect was not affected by distracter salience.