Siblings Of Schizophrenia Patients Research Articles

P518. Face Memory and Emotion Recognition in Individuals Diagnosed With Schizophrenia, Their Unaffected Siblings, Individuals With Ultra-High Risk for Psychosis and Healthy Controls

Face memory and emotion recognition are crucial components of social cognition and interaction. Schizophrenia patients are known to have deficits in these dimensions. However possible link to inherited endophenotypes is unknown. The aim of our study is to compare these dimensions in groups of individuals diagnosed with schizophrenia (SCH), ultra-high risk for psychosis (UHR), unaffected siblings of schizophrenia patients (SSP), and healthy controls (HC).

Prepulse inhibition in first-degree relatives of schizophrenia patients: A systematic review.

Prepulse inhibition (PPI) is a measure of sensorimotor gating used to identify deficits in early-stage information processing and inhibitory function defects. Many studies support the presence of PPI deficits in schizophrenia patients. However, very few studies have explored PPI levels among first-degree relatives (FDR) of schizophrenia patients, and the results have been inconsistent. This review article explored PPI levels in FDR of schizophrenia patients. We performed a systematic literature review using the PubMed, Cochrane, Embase, EBSCO and Chinese databases from inception to January 2020. A series of related factors (eg, PPI paradigm, heritability and sample characteristics) and outcomes were summarized from the literature that met the inclusion criteria. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. A total of eight studies were eligible for systematic review after screening. A meta-analysis of the selected studies was not conducted due to the limitations of quantity and paradigm heterogeneity. A majority of the studies' subjects were siblings of schizophrenia patients and different paradigms were applied. Most of the included studies reported no difference in PPI values between FDR of schizophrenia patients and healthy controls. Contrary to traditional certainty that unaffected FDR of schizophrenia patients have PPI defects, our review found no sufficient evidence supporting that the PPI level in FDR of schizophrenia patients was lower than in healthy controls. A prospective cohort study focusing on different outcomes such as developing schizophrenia is required to explore PPI levels in FDR of schizophrenia patients.

Disrupted upregulation of salience network connectivity during acute stress in siblings of schizophrenia patients

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.

Increased responses of the reward circuitry to positive task feedback following acute stress in healthy controls but not in siblings of schizophrenia patients

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.

At-risk individuals display altered brain activity following stress

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes.

S.16.07 - The dynamic brain response to stress is impaired in siblings of schizophrenia patients

S.16.07 - The dynamic brain response to stress is impaired in siblings of schizophrenia patients

M86. Volumetric Reductions in Global and Regional—Reward Related—Brain Structures in Schizophrenia and Comorbid Metabolic Syndrome

Abstract Background: Metabolic syndrome (MetS) is highly prevalent in schizophrenia. Unhealthy lifestyles, such as overeating, smoking and sedentary behavior are more common in schizophrenia than in the general population and play an important role in the development of MetS (Papanastasiou, 2012). Key to adaptive health behavior is the ability to evaluate reward and risk accurately, which is mediated by the reward circuit in the brain (Haber and Knutson, 2010). This is implicated in schizophrenia (De Leeuw et al., 2014). Examining MetS in relation to these reward areas informs us about the neural circuitry that may drive unhealthy behavior and MetS prevalence in schizophrenia. Methods: Seventy-one patients with schizophrenia (age/SD = 29.6 ± 5.8) were divided in 2 groups, those with MetS (MetS+; n = 23) and without (MetS−; n = 48). With ANCOVAs we examined global structural MRI differences between MetS+ and MetS− groups in volumes of total brain, grey matter, white matter, ventricles, and in regional volumes of orbitofrontal cortex, insula, anterior cingulate cortex, striatum, amygdala and thalamus. Furthermore, as an exploratory step we investigated cortical thickness and surface area of significantly different volumes. Results: Patients with schizophrenia and MetS compared to those without MetS had significantly smaller total brain (P = .016) and grey matter (P = .003) volumes, a larger ventricular volume (P = .012), and smaller orbitofrontal cortex (P = .002) and insula (P = .005) volumes, which was FDR corrected, with age, gender and intracranial volume as covariates. The volume reductions in orbitofrontal cortex and insula were driven by their cortical surface area (P = .007; P = .024, respectively). Conclusion: Patients with schizophrenia and MetS compared to those without MetS had smaller global brain volumes (ie, total brain, grey matter, ventricles) as well as regional structural reductions in orbitofrontal cortex and insula, both structures implicated in the reward circuitry. This suggests that faulty reward circuitry might lead to an increased rate of MetS in schizophrenia.

P.3.029 - Psychosocial stress and emotion processing in siblings of schizophrenia patients

In the context of the EU-DEMO pre-conceptual design phase and the setup of a fuel cycle simulation tool, we analysed twelve prime technology candidates of the fusion fuel cycle to determine the impact of these choices and future R&D priorities. The main function and working principle of these technologies are shortly characterized and two evaluation parameters are introduced: the Technology Readiness Level and the DEMO Importance Level. The former is an approach adapted from literature to evaluate the maturity of a technology in the categories theory, experiments and integration. The latter grades the performance, reliability and impact on system robustness of each technology deriving its criticality. Ultimately, both parameters are combined to form a matrix of research priorities. Technologies of high importance and low maturity, namely the breeding blanket, metal foil pump and thermal cycling absorption process are ranked highest priority. Second priority is given to technologies of lesser criticality and maturity, such as vacuum pumps. Technologies of high maturity and importance are graded third priority. They require proper integration on a system level to counteract the boundary conditions they impose. Last priority is given to well established, reliable technologies such as cryotraps and depleted uranium getter beds.

Changes in event-related potentials in patients with first-episode schizophrenia and their siblings

BackgroundThis study aimed to explore the characteristics of event-related potentials induced by facial emotion recognition in patients with first-episode schizophrenia and in their siblings.MethodsIn this case-control study, 30 first-episode schizophrenia patients, 26 siblings, and 30 healthy controls were enrolled. They completed facial emotion recognition tasks from the Ekman Standard Faces Database as an induction for evoked potentials. Evoked potential data were obtained using a 64-channel electroencephalography system. Average evoked potential waveforms were computed from epochs for each stimulus type. The amplitudes and latency of the event-related potentials for P100 (positive potential 100 ms after stimulus onset), N170 (negative potential 170 ms after stimulus onset), and N250 (fronto-central peak) were investigated at O1, O2, P7, and P8 electrode locations.ResultsThere were significant differences between the groups for P100 amplitude (F = 11.526, P < 0.001), electrode position (F = 450.592, P < 0.001), emotion (disgust vs. happiness vs. fear) (F = 1722.467, P < 0.001), and emotion intensity (low vs. moderate vs. high) (F = 1737.169, P < 0.001). Post hoc analysis showed significantly larger amplitudes in the schizophrenia group at the O1, O2, P7, and P8 electrode positions. There were no significant differences between the siblings of schizophrenia patients and the healthy controls.ConclusionsPatients with schizophrenia showed abnormalities in P100 amplitude, but similar results were not observed in their siblings. These results provide evidence of dysfunctional event-related potential patterns underlying facial emotion processing in patients with schizophrenia. P100 may be a characteristic index of schizophrenia.

Educational achievement in psychiatric patients and their siblings: a register-based study in 30 000 individuals in The Netherlands.

Poor educational achievement is associated with a range of psychiatric disorders. Several studies suggest that this underperformance is due to cognitive deficits that commence before disease onset and reflect a genetic risk for this disorder. However, the specificity and the familial contribution of this cognitive deficit are not clear. We analysed lifetime educational achievement of psychiatric patients diagnosed with schizophrenia, bipolar or depressive disorder and their unaffected siblings. In a register-based case-control study, 1561 patients with schizophrenia, 813 patients with bipolar disorder, 8112 patients with depression, and their siblings were each matched with eight population controls. Patients, siblings and controls were compared on the highest educational stream they completed. Lower educational achievement was present in schizophrenia patients from primary school onwards [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR 0.69; completing academic education: OR 0.46], compared to patients with bipolar disorder or depression. Siblings of schizophrenia, bipolar or depressed patients showed no underachievement at primary or secondary school, but siblings of schizophrenia patients as well as siblings of depressed patients were less successful in their educational achievement after secondary school (completing academic education, schizophrenia siblings: OR 0.90; depressive disorder siblings: OR 0.91). Educational underachievement from primary school onwards is specifically related to schizophrenia and not to bipolar disorder or depression. Moreover, it appears to be a harbinger of the illness, since it is not found in their siblings. These results add to evidence that early cognitive deficits are a distinct feature of the schizophrenia phenotype.

P.1.i.015 - Psychosocial stress and emotion processing in siblings of schizophrenia patients

P.1.i.015 - Psychosocial stress and emotion processing in siblings of schizophrenia patients

The Association between Intelligence Scores and Family History of Psychiatric Disorder in Schizophrenia Patients, Their Siblings and Healthy Controls

BackgroundThe degree of intellectual impairment in schizophrenia patients and their relatives has been suggested to be associated with the degree of familial loading for schizophrenia. Since other psychiatric disorders are also more present in relatives of schizophrenia patients, the definition of family history should be broadened. The association between family history for psychiatric disorder and intelligence scores was investigated in patients with non-affective psychosis, their unaffected siblings and controls.MethodsA sample of 712 schizophrenia proband families (696 patients and 766 siblings) and 427 healthy control families (517 subjects) participated in this study. Family history of psychiatric disorder was determined while excluding the data of the participating schizophrenia patient. A dichotomous division was made between families with no first- or second degree relative with psychiatric disorder and families with one or more affected relatives. Total intelligence scores were estimated by admission of the short form of the Wechsler Adult Intelligence Scale III.ResultsA significant interaction was found between family history of psychiatric disorder and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family history of psychiatric disorder obtained higher intelligence scores compared to patients with no family history (mean IQ scores are 95.52 and 92.72) with an opposite effect in controls (mean IQ scores are 108.71 and 111.19). No significant difference was found between siblings of schizophrenia patients with or without a positive family history (mean IQ scores are 102.98 and 103.24).ConclusionIn patients with schizophrenia, a negative family history of psychiatric disorder was associated with relatively low IQ suggesting that the etiology in these patients may involve environmental or genetic factors which are unique to the patient and are not observed in other relatives. Possible factors include severe environmental stressors containing premature birth or brain injury and genetic factors (e.g de novo Copy Number Variants).

S.07.07 Reward processing in unaffected siblings of schizophrenia patients: a functional magnetic resonance imaging study

S.07.07 Reward processing in unaffected siblings of schizophrenia patients: a functional magnetic resonance imaging study

P.4.006 Reward processing in unaffected siblings of schizophrenia patients: a functional magnetic resonance imaging study

free ethanol consumption, using qRT-PCR, chromatin immunoprecipitation and immunohistochemistry approaches. Increased expression of bHLH transcription factors implicated in neural proliferation and maturation and BDNF occurred concomitantly with increased neurogenesis after free ethanol intake in mice (10% ethanol in drinking water for 3 weeks). In addition, MeCP2 expression was increased at both mRNA and protein levels in the DG and CA3 areas, and upregulation of acetylated histone H4 (H4Ac) and trimethylated histone H3 (H3K4me3) was also noted in these hippocampal areas in ethanol-exposed mice. Thorough analysis of bdnf gene evidenced ethanol-induced modifications at transcription level associated with changes in H3Ac and H3K4me3 at bdnf promoter. Differential expression of bdnf exons appeared causally linked to ethanol-induced increase in BDNF protein in the hilus and CA3 area of the hippocampus. Altogether, these results suggest that chronic moderate ethanol intake under free choice conditions promotes neurogenesis in the DG in C57BL/6J mice by stimulating the expression of neural factors and BDNF. Epigenetic mechanisms involving histone modifications at the level of bdnf gene play probably a key role in ethanol-induced BDNF upregulation in the mouse hippocampus.

Reward processing in unaffected siblings of schizophrenia patients: an fMRI study

Schizophrenia is characterized by a failure in dopaminergic signal transduction. Reward processing is dependent on adequate dopaminergic transduction in mesolimbic and mesocortical pathways and may therefore be affected in schizophrenia. Reward processing can be dived into two sub-processes: anticipation and the receiving of reward. Reward anticipation is thought to be primarily mediated by dopaminergic neurons. Despite abnormal dopamine function in schizophrenia, functional MRI studies in patients during reward anticipation have shown conflicting results: hypoand hyperactivation of the ventral striatum have been reported. This inconsistency may be due to several (illness-related) factors of which the use of dopamine antagonists is probably the most important one. The goal of the current study is to investigate reward (anticipation) processing using fMRI in siblings of schizophrenia patients who share on average 50% of their ill siblings’ genes without having illness-related confounds such as the use of medication.

Facing the Future: Face-Emotion Processing Deficits as a Potential Biomarker For Various Psychiatric and Neurological Disorders

Facing the Future: Face-Emotion Processing Deficits as a Potential Biomarker For Various Psychiatric and Neurological Disorders

Prospective memory in patients with first-onset schizophrenia and their non-psychotic siblings

This behavioral study used a dual-task paradigm to compare PM performance in 35 patients with first-onset schizophrenia, 40 non-psychotic siblings and 35 healthy controls. It aimed specifically to examine the effect of schizophrenia group status on PM, the differential effect of group status on PM type, and correlations between PM and other neurocognitive functions and clinical data in first-onset schizophrenia. It also aimed to test the hypothesis that non-psychotic siblings had poorer PM performance than controls. The cohort of first-onset schizophrenia patients had relatively short illness durations (M=1.7 years). The three groups of participants were matched in terms of age, gender and years of education. Results of the study confirmed that first-onset schizophrenia status had a primary effect on PM after controlling for other neurocognitive functions. We also found that first-onset schizophrenia status did not differentially affect two different types of PM. In the first-onset schizophrenia cohort, PM was found to correlate significantly with IQ, executive functions and sustained attention. Finally, contrary to the findings of the previous study, this study did not find siblings of schizophrenia patients to have impaired PM. Taking into account the previous findings of PM in chronic schizophrenia, we concluded that schizophrenia has a primary effect on PM regardless of illness duration.

Longitudinal alterations of executive function in non-psychotic adolescents at familial risk for schizophrenia

Genetic diathesis to schizophrenia may involve alterations of adolescent neurodevelopment manifesting as cognitive deficits. Brain regions mediating executive function (fronto-striatal circuits) develop during adolescence while those supporting elementary aspects of attention (e.g. sustained focused attention) have a more protracted maturation beginning in childhood. We hence predicted that adolescents at risk for schizophrenia would show a failure of normal maturation of executive function. We prospectively assessed 18 offspring and 6 siblings of schizophrenia patients (HR) and 28 healthy controls at baseline, year-1 and year-2 follow-up using the Continuous Performance Test [visual-d′] and Wisconsin Card Sort Test (WCST). Perseverative errors on the WCST in HR remained stable but decreased in controls over the follow-up (study-group by assessment–time interaction, p = 0.01, controlling for IQ). No significant study-group by assessment-time interactions were seen for sustained attentional performance. HR may not improve while healthy subjects progressively improve on executive function during adolescence and early adulthood. Our results suggest an altered maturational trajectory of executive function during adolescence in individuals at familial risk for schizophrenia.

Psychiatric family history and schizophrenia risk in Denmark: which mental disorders are relevant?

A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples. All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression. Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individual's risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth. Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.

The forgotten caregivers: Siblings of schizophrenic patients

Objective. The situation of caregivers of psychiatric patients is mostly focussed on burdens of parents or spouses of patients. The burden of siblings due to the illness, however, is mostly underestimated and disregarded. Methods. Thirty-seven narrative interviews with siblings of schizophrenia inpatients were analysed by using a summarizing content analysis. The founded global statements were quantitatively analysed. Regression-analysis as well as regression trees were used to evaluate the data linked with sociodemographic and disease-related variables of the patient and siblings. Results. The results showed a high proportion of siblings engaged in caregiving activities. A total of 492 individual statements were summarized in 26 global types of statements. The three most often reported burdens by the healthy siblings are: “Handling the symptoms of illness” (100%), “Emotional burden due to the illness of the sibling” (100%) and “Uncertainty in judging what amount of stress the patient can cope with” (81.1%). Linear regression and regression tree analysis show predictors for higher burdened siblings. Conclusion. Siblings of schizophrenia patients are burdened in various aspects and in a specific matter. Their special needs will therefore have to be recognised before they can receive appropriate intervention.