Relatives Of Schizophrenia Patients Research Articles

Resting-state Functional Connectivity between Dorsolateral Prefrontal Cortex and Left Temporal Language-related Region in Unaffected First-degree Relatives of Schizophrenia Patients

According to the large body of literature data, patients with schizophrenia demonstrate altered (decreased) functional connectivity (FC) between the brain regions involved in executive functions and language (in particular, dorsolateral prefrontal cortex (DLPFC) and left temporal regions). However, the analysis of similar FC in the genetic risk group has not been done, although such data are significant for studying the neurobiological markers of schizophrenia, linked to the genetic architecture of the disorder (its traits or so-called endophenotypes). The aim of this study was to investigate whether FC between the DLPFC and left temporal language-related region was altered in unaffected first-degree relatives of patients with schizophrenia. First-degree unaffected relatives of patients with schizophrenia (12 subjects) and healthy individuals without family history of mental disorders (13 subjects) underwent resting-state functional magnetic resonance imaging at 3T Philips scanner. The FC between the regions of interest (left/right DLPFC, on the one hand, and left temporal region, on the other hand) was compared between groups as well as indexes of Verbal fluency and the Scale of Prodromal Symptoms (SOPS). As compared to controls, the relatives of patients with schizophrenia were characterized by increased FC between the left DLPFC and left temporal language-related region, although they did not differ in the other indexes, and there were no correlations between the indexes and FC. The findings might reflect some compensatory functional processes in unaffected first-degree relatives of schizophrenic patients.

P.4.14 An investigation of retinal layer thicknesses in unaffected first degree relatives of schizophrenia patients

P.4.14 An investigation of retinal layer thicknesses in unaffected first degree relatives of schizophrenia patients

The effects of psychological help on assertive behaviors in family members of schizophrenia patients.

The aim of this study was to determine the relationship between the use (or lack thereof) of psychological help among family members of schizophrenia patients, and their expression of assertive behavior in relation to their relatives suffering from the illness. The study group consisted of 34 people who run the household with their loved ones - schizophrenia patients. In the study we used the Social Competence Questionnaire (KKS) by Matczak, and the Coping Inventory for Stressful Situations (CISS) in the Polish adaptation by Wrześniewski et al. Socio-demographic data were collected through a self-designed survey. There was a relationship between a general tendency to avoid action in a problem situation and a tendency to seek social diversion in order to cope with stress. Assertive behavior was also found to correlate with a tendency to engage in substitute activities. Greater willingness to display assertive behavior was observed in subjects who revealed a tendency to avoid thinking about the problem and seeking active solutions in a stressful situation. The analyses also showed that younger people who coped with stress by revealing an avoidant coping style exhibited a more assertive behavior. Our study did not confirm the link between the use of psychological assistance by the relatives of schizophrenia patients and their expression of assertive behavior in relation to the patient. However, it proved important that younger people who coped with stress by means of avoidance-oriented strategies manifested a greater propensity for assertive behavior.

Temporal lobe thickness and verbal memory in first-degree relatives of individuals with schizophrenia

Cortical thinning in frontal and temporal regions has been reported in individuals diagnosed with schizophrenia and, less consistently, among their unaffected first-degree relatives. Likewise, first-degree relatives demonstrate attenuated differences in neurocognitive performance relative to healthy controls, indicating that neurocognitive performance may be an important endophenotype of the disorder. Less is known about how cortical thickness relates to neurocognitive performance in these individuals. Given the robust nature of temporal structural abnormalities in schizophrenia, this study aimed to identify how temporal lobe cortical thickness might relate to verbal memory in first-degree relatives. Unaffected parents and siblings of individuals with adult-onset schizophrenia (N=62) and individuals in healthy control families (N=70) participating in the UCLA Family Study received a structural MRI and completed a battery of neurocognitive tests. Cortical thickness was estimated across the cortex and thickness measures of all regions in the temporal lobe were summed, averaged, and residualized for age and sex to produce a variable. A verbal learning factor was derived from two common tests of verbal learning and memory, the CVLT-II and Logical Memory of the WMS-III. Results demonstrated a significant interaction between group and verbal learning in relationship to temporal lobe thickness. Post-hoc analyses revealed significant correlations between verbal learning and cortical thickness in the relatives of schizophrenia patients which were driven by immediate recall scores on the CVLT-II and Logical Memory. These findings indicate that cortical thickness in the temporal cortex may represent a structural correlate for encoding verbal information in unaffected relatives of individuals with schizophrenia.

SA95. A Tale of 2 Endophenotypes in Clinically Unaffected Relatives of Schizophrenia Patients

SA95. A Tale of 2 Endophenotypes in Clinically Unaffected Relatives of Schizophrenia Patients

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

Higher N1 responses in relatives of schizophrenia patients than controls in visual backward masking

Higher N1 responses in relatives of schizophrenia patients than controls in visual backward masking

Anterior Cingulate Cortico-Hippocampal Dysconnectivity in Unaffected Relatives of Schizophrenia Patients: A Stochastic Dynamic Causal Modeling Study

Familial risk plays a significant role in the etiology of schizophrenia (SZ). Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC), caudate, dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs) in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients—according to the DSM-IV—were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI). We used stochastic dynamic causal modeling (sDCM) to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ.

Counterfactual Reasoning in Non-psychotic First-Degree Relatives of People with Schizophrenia.

Counterfactual thinking (CFT) is a type of conditional reasoning that enables the generation of mental simulations of alternatives to past factual events. Previous research has found this cognitive feature to be disrupted in schizophrenia (Hooker et al., 2000; Contreras et al., 2016). At the same time, the study of cognitive deficits in unaffected relatives of people with schizophrenia has significantly increased, supporting its potential endophenotypic role in this disorder. Using an exploratory approach, the current study examined CFT for the first time in a sample of non-psychotic first-degree relatives of schizophrenia patients (N = 43), in comparison with schizophrenia patients (N = 54) and healthy controls (N = 44). A series of tests that assessed the “causal order effect” in CFT and the ability to generate counterfactual thoughts and counterfactually derive inferences using the Counterfactual Inference Test was completed. Associations with variables of basic and social cognition, levels of schizotypy and psychotic-like experiences in addition to clinical and socio-demographic characteristics were also explored. Findings showed that first-degree relatives generated a lower number of counterfactual thoughts than controls, and were more adept at counterfactually deriving inferences, specifically in the scenarios related to regret and to judgments of avoidance in an unusual situation. No other significant results were found. These preliminary findings suggest that non-psychotic first-degree relatives of schizophrenia patients show a subtle disruption of global counterfactual thinking compared with what is normally expected in the general population. Due to the potential impact of such deficits, new treatments targeting CFT improvement might be considered in future management strategies.

Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals.

A substantial proportion of schizophrenia liability can be explained by additive genetic factors. Risk profile scores (RPS) directly index risk using a summated total of common risk variants weighted by their effect. Previous studies suggest that schizophrenia RPS predict alterations to neural networks that support working memory and verbal fluency. In this study, we apply schizophrenia RPS to fMRI data to elucidate the effects of polygenic risk on functional brain networks during a probabilistic‐learning neuroimaging paradigm. The neural networks recruited during this paradigm have previously been shown to be altered to unmedicated schizophrenia patients and relatives of schizophrenia patients, which may reflect genetic susceptibility. We created schizophrenia RPS using summary data from the Psychiatric Genetic Consortium (Schizophrenia Working Group) for 83 healthy individuals and explore associations between schizophrenia RPS and blood oxygen level dependency (BOLD) during periods of choice behavior (switch–stay) and reflection upon choice outcome (reward–punishment). We show that schizophrenia RPS is associated with alterations in the frontal pole (P WHOLE‐BRAIN‐CORRECTED = 0.048) and the ventral striatum (P ROI‐CORRECTED = 0.036), during choice behavior, but not choice outcome. We suggest that the common risk variants that increase susceptibility to schizophrenia can be associated with alterations in the neural circuitry that support the processing of changing reward contingencies. Hum Brain Mapp 37:491–500, 2016. © 2015 Wiley Periodicals, Inc.

IQ as a Cognitive Marker of Genetic Liability in Relatives of Schizophrenia Patients.

IQ as a Cognitive Marker of Genetic Liability in Relatives of Schizophrenia Patients.

P169. Impaired gesture performance as potential endophenotype of schizophrenia

Introduction Disturbed social functioning including nonverbal communication is a core characteristic of schizophrenia. One crucial factor of nonverbal communication is gesturing. Gesturing is impaired in patients with schizophrenia. We aimed to test whether impairments in gesture performance would be present in unaffected first degree relatives of schizophrenia patients and could therefore be a potential marker of the disorder. Method We investigated 29 unaffected first degree relatives of schizophrenia patients and 29 control subjects matched for age, gender, education level, nonverbal intelligence and income. Participants performed a comprehensive test for gesture performance the Test of Upper Limb Apraxia (TULIA) ( Vanbellingen et al., 2010 ). In brief, the TULIA assesses the performance of gestures in two principal domains, i.e. imitation (production after demonstration) and pantomime (production following verbal instruction). For both domains three semantic subgroups were tested: meaningless, transitive (tool related) and intransitive (symbolic non-tool related) gestures. In addition motor behavior, working memory and frontal lobe function was assessed. Furthermore psychic experience was assessed in first degree relatives. Results First degree relatives of schizophrenia patients showed relatively severe difficulties during gesture performance. In fact, 24% of the relatives scored below the cut-off scores. In addition motor behavior was impaired in relatives. Relatives showed abnormal involuntary movements (AIMS), neurological soft signs (NSS) and abnormalities in movement (Modified Rogers Scale, MRS) as more prevalent. Moreover gesturing was predicted by impaired motor behavior in relatives. Conclusions Gesture performance impairment has been shown in unaffected first degree relatives of schizophrenia patients. Furthermore poor gesturing was associated with impaired motor behavior in first degree relatives. Our results indicate that deficits of gesturing could be linked to motor functioning. Moreover gesturing could present a potential maker of vulnerability for schizophrenia ( Table 1 ).

Working memory impairment in probands with schizoaffective disorder and first degree relatives of schizophrenia probands extend beyond deficits predicted by generalized neuropsychological impairment

ObjectiveWorking memory impairment is well established in psychotic disorders. However, the relative magnitude, diagnostic specificity, familiality pattern, and degree of independence from generalized cognitive deficits across psychotic disorders remain unclear. MethodParticipants from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study included probands with schizophrenia (N=289), psychotic bipolar disorder (N=227), schizoaffective disorder (N=165), their first-degree relatives (N=315, N=259, N=193, respectively), and healthy controls (N=289). All were administered the WMS-III Spatial Span working memory test and the Brief Assessment of Cognition in Schizophrenia (BACS) battery. ResultsAll proband groups displayed significant deficits for both forward and backward span compared to controls. However, after covarying for generalized cognitive impairments (BACS composite), all proband groups showed a 74% or greater effect size reduction with only schizoaffective probands showing residual backward span deficits compared to controls. Significant familiality was seen in schizophrenia and bipolar pedigrees. In relatives, both forward and backward span deficits were again attenuated after covarying BACS scores and residual backward span deficits were seen in relatives of schizophrenia patients. ConclusionsOverall, both probands and relatives showed a similar pattern of robust working memory deficits that were largely attenuated when controlling for generalized cognitive deficits.

Endophenotypic Markers in the Relatives of Schizophrenia Patients: Systematic Reviews of Theory of Mind and Informative Morphogenetic Variant Studies

Introduction The endophenotype concept of schizophrenia represents an important approach in the exploration of the neurobiology of the illness. An important characteristic of an endophenotype, that it can be found among the healthy, first-degree relatives of patients with schizophrenia. Objectives We evaluated two systematic reviews of studies on two potential endophenotypes (theory of mind and informative morphogenetic variants) to confirm the possibility of them as biological and cognitive markers of the illness. Aims We planned to explore data from theory of mind and informative morphogenetic variant studies among the relatives of schizophrenia patients. Methods We evaluated two researches of studies published in PubMed, Medline,Web of Science and PsycINFO between the period of 1968 and 2014 (informative morphogenetic variants studies) and 1980 and 2014 (theory of mind studies). Results 11 studies on the appearence of informative morphogenetic variants in the relatives of schizophrenia patients were found with mixed results, while 15 studies and two meta-analyses were analysed on theory of mind studies among the first-degree relatives of patients with schizophrenia,the exploration of the latter studies showed also diverse findings. Conclusion Futher research is needed to clarify theory of mind and informative morphogentic variant alternations as endophenotypic markers of schizophrenia. Acknowledgement: This study was supported by the National Brain Research Program Grant no. NAP KTIA NAP-A-II/12.

The Importance of Research on the Relatives of Schizophrenia Patients ? Towards Endophenotypic Markers

The endophenotype concept of schizophrenia represents an important approach in the exploration of the neurobiology of the illness. Gottesman and Shields (2003) described an endophenotype as an internal, intermediate phenotype (i.e., not obvious to the unaided eye) that fills the gap between genes and diseases. Endophenotypes should be: (1) associated with the illness in the population, (2) heritable, (3) state-independent, (4) found in unaffected family members at a higher rate than in the general population, and (5) shown to cosegregate with the illness within families. As we can see an important characteristic of an endophenotype, that it can be found among the healthy, first-degree relatives of patients with schizophrenia. Minor physical anomalies (MPAs) and social cognition (SG) are suggested as endophenotypes on account of the findings that MPAs and SG deficits are more common in schizophrenia patients than in healthy controls, which can be found also in remission and in few studies higher prevalences were found in healthy first-degree relatives

Neural responses during social reflection in relatives of schizophrenia patients: Relationship to subclinical delusions

BackgroundDeficits in the capacity to reflect about the self and others (“social reflection” [SR]) have been identified in schizophrenia, as well as in people with a genetic or clinical risk for the disorder. However, the neural underpinnings of these abnormalities are incompletely understood. MethodsResponses of a network of brain regions known to be involved in self and other processing (e.g., medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and superior temporal gyrus (STG)) were measured during SR in 16 first-degree, non-psychotic relatives (RELS) of schizophrenia patients and 16 healthy controls (CONS). Because of prior evidence linking dysfunction in this network and delusions, associations between SR-related responses of this network and subclinical delusions (measured using the Peters et al. Delusions Inventory) were also examined. ResultsCompared with CONS, RELS showed significantly less SR-related activity of the right and left PCC and STG. Moreover, response magnitudes were negatively correlated with levels of delusional thinking across both groups. ConclusionsThese findings suggest that aberrant function of the neural circuitry underpinning SR is associated with the genetic liability to schizophrenia and confers vulnerability to delusional beliefs.

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).

Altered immune function in relatives of schizophrenia patients

Altered immune function in relatives of schizophrenia patients

Psychopathology: genetics and the stress-vulnerability hypothesis

Since the findings of dopamine blockade by antipsychotics, a dysfunction of the dopamine system has been proposed to underly psychopathological symptoms in schizophrenia. In SPECT and PET imaging studies, radioligand binding to the dopamine receptor or transporter reflects the occupancy by dopamine itself or antipsychotics. Using dual-isotope imaging for the evaluation of pre- and postsynaptic site, Schmitt et al. [1] examined striatal dopamine transporter and dopamine D2 receptor availability in first-episode schizophrenia patients and patients with haloperidol treatment compared to healthy controls. In drug-naive patients with positive symptoms, dopamine transporter availability correlated negatively with psychopathology as did D2 receptor binding with disorganization and hallucinatory behavior, thus strengthening the dopamine hypothesis for positive symptoms. D2 receptor and dopamine transporter availability was lower in the haloperidol group which confirms previous dopamine blockade studies. However, response to antipsychotics is individual, and genetic factors may contribute to a different outcome. Mossner et al. [2] reported that patients homozygous for the risk allele ZNF804A show poorer improvement of positive symptoms compared to patients with a protective allele. Thus, identification of risk genes may help identifying patients with a different course of the disorder. A pharmacogenetic study of Crisafulli et al. [3] investigated 10 SNPs of genes related to pathophysiological pathways in Korean patients. They found a SNP within 5HTR1A associated with clinical improvement in both positive and negative symptoms. In schizophrenia patients, improvement of quality of life as treatment outcome among others is dependent on support in case of problems and assistance in coping with daily life demands. Landolt et al. [4] revealed that unmet needs changing to fulfilled ones enhanced quality of life. In this context, psychosocial functioning and psychotic symptoms may be influenced by alterations of theory of mind and empathy as underlying social-cognitive deficits and possibly are heritable. In first-degree relatives of schizophrenia patients, Montag et al. [5] showed impairment in cognitive skills, suggesting that social-cognitive abilities may serve as an intermediate phenotype for schizophrenia. In a re-analysis of AMDP data by nonmetric multidimensional scaling, Lage et al. [6] replicated clusters of psychopathological symptoms in two independent samples dating from 1980 and 2003. In individual’s health, the psychological well-being dimension and depressive symptoms are important variables and Morelatto de Souza and Paz Loayza Hidalgo [7] validated the WHO well-being index in a Brazilian population and showed this scale to be a useful tool for screening of depressive symptoms. Hagihara and Abe [8] highlight the influence of media reports on suicide and counteracting effects of stopping the sale of suicide-related products in Japan. Beside genetics, stressful experience and trauma are risk factors for the development of psychiatric diseases. Linden et al. [9] analyzed 100 case files of German servicemen during World War I and classified them in agreement with modern diagnoses. Most ancient diagnoses were “psychopathic constitution” or “hysteria.” Using contemporary diagnostics, some of these soldiers had symptoms of post-traumatic stress disorder. There was a high incidence of pseudoseizures that highlights different human responses to traumatic experience and stress in a historical context. Stressful experiences are known to increase vulnerability to schizophrenia. Rossi et al. [10] evaluated the Community Assessment of Psychic Experiences (CAPE) in students who survived an earthquake 2009 in Italy. Unexpectedly, earth quake survivors showed lower CAPE scores than nonexposed subjects. This is in line with the hypothesis that stressful events preceding psychosis are not derived from external traumatic experiences. In a previous study, Puustinen et al. [11] reported C-reactive protein, marker of cardiovascular disease, to be associated with psychological distress. However, in a cross-sectional and 3-year follow-up study in Japanese male workers, Kawada [12] failed to show this relationship, which is probably due to ethnicity. Life experience, stressful events and other environmental factors are known to influence the risk of developing mental diseases. The missing link between environment and neurobiology may be explained by epigenetic mechanisms, such as DNA methylation and acetylation in disease-related brain regions. Wiers [13] refers to an fMRI study of the COMT gene with the Val allele being associated with DNA methylation [14]. She proposes the use of genetic imaging in combination with investigations of epigenetic markers in blood cells to unravel gene-environmental interactions in severe psychiatric disorders.

AS21-01 - Alterations of the early auditory evoked gamma-band response in patients with schizophrenia

There is growing evidence of abnormalities of high-frequency oscillations in the gamma range of the electroencephalography in schizophrenia. The generation of neural activity in the gammaband was shown to be critically related to a glutamatergic and GABAergic microcircuit which is also known to be involved in the pathophysiology of schizophrenia. One example of such gamma oscillations is the early auditory evoked gamma band response (aeGBR). We aimed to investigate whether there are altered aeGBR and activity of its sources in the anterior cingulate cortex and/or the auditory cortex (identified as sources of the GBR previously) in schizophrenic patients and in first-degree relatives of schizophrenia patients. We investigated the early aeGBR and its sources (LORETA source localisation) in 90 medicated patients with schizophrenia and in 17 unaffected first-degree relatives of patients with schizophrenia using an auditory reaction task (comparison with age-, gender- and educational-level-matched control groups). Evoked power and phase locking of the aeGBR was reduced in schizophrenia patients and healthy first-degree relatives of patients with schizophrenia. This effect was due to a reduced activity in the auditory cortex and the anterior cingulate cortex. The findings are in line with the hypothesis of a disturbed GABAergic interneural modulation of pyramidal cells in schizophrenia and findings of different schizophrenia risk genes associated with transmission at glutamatergic and GABAergic synapses. The results regarding the first-degree relatives of patients with schizophrenia point to the applicability of this marker as a heritable intermediate phenotype for schizophrenia.