First-degree Relatives Of Schizophrenia Patients Research Articles

Mismatch Negativity in Schizophrenia, Unaffected First-degree Relatives, and Healthy Controls

BackgroundMismatch negativity (MMN) amplitude is attenuated in schizophrenia patients (SZ). However, variability in illness course among SZ samples and types of deviant stimuli used in MMN paradigms have contributed to inconsistent findings across studies. Though MMN is suggested to be impaired in schizotypy, the potential link between the two is yet to be systematically examined in unaffected first-degree relatives of schizophrenia patients (FDR). MethodsThe SZ sample had twenty-two drug-naïve or drug-free patients (dSZ) and thirty chronic/medicated patients (cSZ). dSZ and cSZ patients were compared with thirty-six unaffected FDR and thirty-two healthy controls (HC) using a two-tone passive auditory oddball MMN paradigm in an event-related potential experiment with two conditions (presented as separate blocks)–duration-deviant (duration-MMN) and frequency-deviant (frequency-MMN). Schizotypy scores and MMN indices were examined for correlation in FDR. ResultsDuration-MMN amplitude was significantly attenuated in both dSZ and cSZ compared to other groups. dSZ and cSZ did not differ on MMN indices. Psychopathology scores and features of illness (illness duration, medication dosage, etc.) did not correlate with MMN indices. In FDR, Schizotypal trait measures did not correlate with MMN indices. ConclusionsDuration-MMN emerged as a more robust indicator of prediction error signalling deficit in SZ. Frequency-MMN amplitude did not significantly differ among the groups, and MMN indices did not correlate with state and trait measures of schizophrenia-related psychopathology. These findings reiterates that auditory sensory processing captured by MMN is likely reflective of dynamic cognitive functions at the point of testing, and is unlikely to be an expression of enduring symptomatology.

Changes in patterns of age-related network connectivity are associated with risk for schizophrenia

Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R2 varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.

A comparative study of theory of mind in taxon-like clusters of psychometric schizotypes and individuals at genetic risk for schizophrenia

ABSTRACT Introduction: Clinical and family studies suggest that alterations of theory of mind (ToM) represent a marker of genetic liability to schizophrenia. Findings regarding ToM in schizotypy are less consistent. The study aimed to explore whether this might be due to an insufficient account of the heterogeneity of schizotypy in prior research and/or the fact that in psychometric schizotypy ToM alterations could manifest as subtle peculiarities rather than overt errors of mentalising.Methods: Individuals without a family history of psychosis (n = 150) were assigned to low, positive, negative, and high mixed schizotypy classes based on a cluster analysis of 1322 subjects who completed the Schizotypal Personality Questionnaire. The classes were compared on their performance of faux pas tasks with 77 adult first-degree relatives of schizophrenia patients, who represent individuals at genetic risk for schizophrenia. Besides overt errors, subtle alterations in ToM were analysed using expert judgment.Results: The relatives tended to make overt errors and demonstrated specific features of intentional reasoning. None of the schizotypal classes showed similar trends.Conclusions: The results complement the literature on the subjective-objective disjunction in psychometric schizotypes and did not provide evidence that ToM anomalies are a marker of genetic liability to schizophrenia in this cohort.

Neurocognitive functioning in adult and adolescent offspring of parents with schizophrenia

IntroductionNeurocognitive deficits have been proposed as endophenotypes for schizophrenia. Although neurocognitive functioning has been studied extensively in first-degree relatives of schizophrenia patients at single time points, little is known about the change or continuity in deficits across development. MethodThe longitudinal sample was composed of 86 nonpsychotic participants who had a parent with schizophrenia (n = 28), a parent with a nonschizophrenia mental disorder (n = 31) or parents without mental illness (n = 27). Executive functioning (EF) was assessed during adolescence (M = 18 years) and adulthood (M = 32 years); attention and memory were assessed at adulthood. ResultsThe schizophrenia group, as adults, showed deficits in attention and memory relative to the no mental illness group. Only on one memory task did the schizophrenia group perform more poorly than the other mental illness group. Executive functioning improved with age for all three groups on Wisconsin Card Sorting Test perseverative errors; the rate of improvement was significantly slower for the schizophrenia and the other mental illness groups, compared to the no mental illness group. Stability in EF functioning over the 16-year period, measured by intraclass correlations, was low. ConclusionsAdults at familial risk for schizophrenia showed deficits in neurocognitive functioning. The similarity of performance between those whose parents had schizophrenia and those whose parents had other mental illness, in all but the measures of memory, raises the question as to whether the neurocognitive functions examined are endophenotypes of vulnerability to schizophrenia specifically. Modest stability of EF and improved performance with age may reflect cortical maturation during early adulthood.

Emotion identification and mentalization in non-psychotic first-degree relatives of young adult patients with schizophrenia disorder

BackgroundSocial cognition is a multi-factorial construct defined as the ability to process social information for adaptive functioning. A large body of evidence acknowledges deficits in social cognition as important features in schizophrenia and that such impairment represent a trait deficit. The aim of this study is to assess two social cognitive functions (emotional identification and mentalization) in young non-psychotic first-degree relatives of patients with schizophrenia; and to compare their performance with that of young patients with schizophrenia as well as with young healthy controls. This a comparative, cross-sectional study including 30 young patients with age range 15–25 with schizophrenia disorder, Thirty young non-psychotic siblings of the patients and 30 young healthy subjects. The patients were subjected to PANNNS to assess severity of psychotic symptoms. Selected tests for assessment of basic cognitive abilities and social cognitive functions (using Reading Mind in the Eye Test, Emotion Identification Test and Emotional Intelligence scale) were used for the three groups.Resultsthe relatives group show better performance than the patients groups and worse performance than the control group in subtests of basic cognition and social cognition functions using Reading Mind in the Eye Test and Ekman, in addition, there was negative correlation between severity of negative psychotic features and facial emotional identification as measured by Ekman.ConclusionYouth who are first-degree relatives of schizophrenia patients show social cognitive deficits, supporting the hypothesis of the role of social cognition impairment as endophenotypic trait in schizophrenia disorder.

Subjective Cognitive Complaints in Unaffected First-Degree Relatives of Schizophrenia Patients: Relation to Cognitive Performance, Psychotic Experiences, and Social Functioning.

Background:Neurocognitive deficits are well-documented in patients of schizophrenia and their first-degree relatives (FDRs). Metacognitive awareness of these deficits, called neurocognitive insight (NI), has been found to be poor in schizophrenia patients but has not been assessed in their FDRs. This study evaluated NI and its relationship with objective cognitive performance, a history of psychotic experiences (PEs), and social functioning in unaffected FDRs.Methods:This cross-sectional study was conducted at the outpatient department of a tertiary care teaching hospital. A total of 100 FDRs were assessed for PEs and evaluated for subjective cognitive complaints (SCC), objective cognitive performance, and social functioning using the Subjective Scale to Investigate Cognition in Schizophrenia, neurocognitive tests from the National Institute of Mental Health and Neurosciences battery, and SCARF Social Functioning Index, respectively.Results:Compared to normative data, episodic memory was the most commonly impaired domain (up to 72% of participants), followed by working memory, attention, and executive function. There was no correlation between SCC and neuropsychological test scores in the corresponding cognitive domains, implying poor NI. 15% of participants had a lifetime history of PEs. This group had significantly higher SCC as compared to those without PEs (U = 0.366, P = 0.009, r = 0.26). A regression analysis showed that the FDRs’ social functioning reduced by 0.178 units for each unit increase in SCC [F (1,98) = 5.198, P = 0.025].Conclusion:Similar to schizophrenia patients, FDRs also have poor NI. The severity and progression of SCC could be explored as a possible marker for screening and monitoring FDRs at an ultrahigh risk for psychosis. Importantly, even in unaffected FDRs, SCC could affect socio-occupational functioning and need further research.

Pro-inflammatory cytokine alterations in unaffected first-degree relatives of schizophrenia patients

IntroductionA growing body of evidence in both chronic and first-episode schizophrenia report increased expression of pro-inflammatory substances in the blood and cerebrospinal fluid of patients. However, there is not much data in the literature on immune alterations in unaffected first-degree relatives (FDRs) of the patients.ObjectivesWe aimed to evaluate inflammatory aberrancies in patients with schizophrenia, their unaffected first-degree relatives (FDRs) and healthy controls.Methods50 chronic, stable schizophrenia patients, 42 FDRs and 40 healthy subjects with no family history (HCSs) were recruited to the study. IL-1β, IL-6, TNF-a and CRP levels were measured. Complete blood counts, fasting glucose and lipid levels were analyzed and neutrofil-lymohocyte ratio (NLR) were calculated.ResultsThere was a significant group difference in all cytokine levels after controlling for age, gender, smoking status, comorbid medical diseases, BMI and blood glucose and tyrigliseride levels (p<.001). FDRs showed significantly higher serum levels of cytokines than HCs, in the same way as the corresponding schizophrenia patients but a lower level. Pairwaise comparisions revealed that the differences were significant between each group after controlling for confounders (p<.001 for all comparisons). However, NLR and CRP levels were not different between groups.ConclusionsOur results support the role of inflammatory aberrancies in the pathophysiology of schizophrenia. The finding of abnormal cytokine levels both in schizophrenic patients and FDRs indicates that such immunological alterations are not exclusive to the patients and can be possible endophenotypes for the disorder.DisclosureNo significant relationships.

Study Family History of Psychiatry Disorders in Schizophrenia Patients

Background: Schizophrenia is a chronic heterogeneous mental disorder that often has debilitating long-term outcomes. Our aim in this study is to survey history of psychiatric disorders in first-degree relatives of schizophrenia patients and its association with the disease clinical and demographic profile. Methods: In this retrospective study the hospital records of all schizophrenia patients that had been admitted in Ibn Sina Psychiatric Hospital from March 2018 to March 2019 were surveyed. Histories of any psychiatry disorders in the first-degree relatives of the schizophrenia patients were searched. The patients with positive family history were compared with those with negative family history in regard to age of onset, sex, negative symptoms, substance abuse and education level. Results: Of 250 files that were studied, 62 (24.2%) patients had family history of psychiatry disorders. Schizophrenia (10.8%), schizoaffective disorder (7.2%) and bipolar disorder (4.2%) were the most common psychiatry disorders in first-degree relatives of schizophrenia patients. Male sex, lower age at onset, substance abuse, negative symptoms, and lower education were more frequently observed in schizophrenia patients with positive family history. Conclusions: Our study demonstrated that family histories of schizophrenia, schizoaffective and bipolar disorder were higher in family history of schizophrenia patients than normal population. Furthermore, positive family history for psychiatric disorder is associated with worse prognosis in schizophrenia patients. J Neurol Res. 2020;10(6):231-234 doi: https://doi.org/10.14740/jnr631

Extending schizophrenia diagnostic model to predict schizotypy in first-degree relatives

Recently, we developed a machine-learning algorithm “EMPaSchiz” that learns, from a training set of schizophrenia patients and healthy individuals, a model that predicts if a novel individual has schizophrenia, based on features extracted from his/her resting-state functional magnetic resonance imaging. In this study, we apply this learned model to first-degree relatives of schizophrenia patients, who were found to not have active psychosis or schizophrenia. We observe that the participants that this model classified as schizophrenia patients had significantly higher “schizotypal personality scores” than those who were not. Further, the “EMPaSchiz probability score” for schizophrenia status was significantly correlated with schizotypal personality score. This demonstrates the potential of machine-learned diagnostic models to predict state-independent vulnerability, even when symptoms do not meet the full criteria for clinical diagnosis.

Nonverbal communication remains untouched: No beneficial effect of symptomatic improvement on poor gesture performance in schizophrenia

BackgroundGestures are an important part of communication. Patients with schizophrenia present gesture deficits that tend to deteriorate in the course of the disease and hamper functional outcome. This gesture deficit has been associated with motor abnormalities, cognitive impairment, and psychotic symptoms. Unaffected, first-degree relatives of schizophrenia patients share some subclinical motor and cognitive abnormalities. We aimed to investigate, whether gesture performance changes with symptomatic improvement in patients, and to test the longitudinal performance in unaffected, first-degree relatives. MethodsIn this study, we measured gesture performance using a validated test in 33 patients, 29 first-degree relatives and 38 healthy controls. Measurements were completed shortly after admission and before discharge in patients. Performance was rated blindly by experts using video recordings of the gesture task. Additionally, we evaluated cognitive function and psychotic symptoms at both visits. ResultsGesture performance was poorer in relatives compared to controls and poorer in patients compared to both relatives and controls. Patients showed an improvement in psychopathology but a significant decrease in gesture performance at follow-up, while performance in the other groups remained stable. Proportional change of gesture performance correlated with change of cognitive function in patients, whereas there were no correlations with change of cognitive function in the other groups. ConclusionWhile symptom severity was reduced, the gesture deficit further deteriorated in schizophrenia. The finding argues for distinct processes contributing to poor nonverbal communication skills in patients, requiring novel alternative treatment efforts.

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.

M224. LONGITUDINAL DETERIORATION OF GESTURE PERFORMANCE IN SCHIZOPHRENIA IS UNRELATED TO SYMPTOM TRAJECTORIES

BackgroundGesture deficits in patients with schizophrenia are highly pronounced, and often linked to poor social functioning, motor abnormalities, and frontal lobe dysfunction. Although gesture performance has been associated to both negative and positive symptoms, its relationship to the severity of these symptoms is still unclear. Here, we examine how gesture performance varies as symptoms change. Furthermore, we aimed to compare gesture performance at two time points to healthy controls and first-degree relatives of schizophrenia patients. Gesture performance in relatives may indicate whether the deficits are associated with genetic liability to schizophrenia. We hypothesize that gesture performance in controls and relatives would be stable; while we expect improvement in patients when symptom severity declines.MethodsThe present study included 36 patients with schizophrenia (DSM-5 criteria; mean age 35.5 years), 28 unaffected first-degree relatives of schizophrenia patients (mean age 49.9 years) and 38 healthy controls (mean age 39.9 years). All three groups performed the Test for Upper-Limp Apraxia (TULIA), which includes pantomime (performance on verbal command) and imitative (performance upon demonstration) gestures, at two different time points, baseline and re-test (between 1–4 weeks). TULIA performance is recorded on videos and rated blind to diagnosis and stage. In addition, 22 of the 36 patients performed the TULIA at a follow-up session 6-months after baseline. Symptom severity was assessed with the Positive And Negative Syndrome Scale (PANSS). Analysis between the three groups and within patients across the different time points was done using repeated measures ANOVA in R.ResultsSymptom severity in patients declined between baseline and week 4 (T = 6.7, p<0.001, PANSS total). A 3x2x2 repeated measures ANOVA revealed significant main effects of Group, Type of Gestures, as well as, a significant interaction between Group and Time Point (all F > 3.8; p<0.5) Post hoc analysis, bonferroni corrected, revealed that patients underperformed in both pantomime and imitative gestures compared to healthy controls (p<0.0001) and relatives of schizophrenia patients, although this effect did not reach significance (p=0.26). Performance of pantomime gestures was poorer compared to imitative gestures. Interestingly, this pattern was also observed during the re-test time point (p<0.0001), though gesture performance for imitative gestures significantly declined compared to baseline in patients (p<0.05). In contrast, healthy controls performed better than both patients (p<0.0001) and relatives (p-0.09) and remained stable during the re-test. Likewise, relatives performed intermediate between patients and healthy controls at both time points with scores reaching significance only at re-test (p<0.001). At baseline, imitation was better than pantomime in relatives, but with re-test imitation scores declined while pantomime scores remained stable. Finally, at the 6-month follow-up patients still exhibited lower gesture performance compared to baseline (F=22.25; p<0.05).DiscussionGesture performance in schizophrenia patients remained significantly impaired across time-points, suggesting an extended effect on poor social functioning despite symptom change. In addition, schizophrenia patients and their relatives showed a significant impairment when performing imitative gestures during the re-test compared to baseline. These results call for interventions specifically targeting gesture and social cognition, which would greatly improve patients’ quality of life. Finally, our findings suggest a trait component to gesture behavior that might be linked to genetic liability to psychosis.

An investigation of retinal layer thicknesses in unaffected first-degree relatives of schizophrenia patients

IntroductionA large number of studies using different neuroimaging methods showed various structural changes both in patients and their unaffected first-degree relatives (FDRs) over the past years. Optical coherence tomography (OCT) is a relatively new, non-invasive imaging method used to obtain high-resolution cross-sectional images of the retina. A growing body of evidence reports thinning of retinal layers in patients with schizophrenia which is considered as a proxy for CNS alterations. We hypothesized that retinal layer changes would be observed in FDRs, in parallel with those seen in patients, as a potential endophenotype candidate. MethodsThirty-eight schizophrenia patients, 38 FDRs of schizophrenia and 38 age and gender-matched healthy subjects with no family history (HCs) were recruited to this study. OCT measurements were performed and peripapillary retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and macular thicknesses were measured. ResultsThe groups did not differ on RNFL, macular or GCL thickness. However, IPL thickness was significantly lower in both patients and FDRs than HCs (p = .025 and p = .041, respectively). The difference between groups remained significant after controlling for confounders such as age, gender, smoking status, comorbid medical diseases and BMI (p = .016 patients vs HCs and p = .014 FDRs vs HCs). ConclusionOur findings suggest that IPL thinning may hold promise as a useful endophenotype for genetic and early detection studies. The evaluation of this area could provide an important avenue for elucidating some of the neurodevelopmental aberrations in the disorder.

The relationship between resting electroencephalogram oscillatory abnormalities and schizotypal personality traits in the first-degree relatives of schizophrenia patients.

Although a large amount of studies have manifested resting state electroencephalogram oscillatory abnormalities in schizophrenia and their first-degree relatives and in schizotype, the results are far from consistent and no research found any relationship between electroencephalograph (EEG) abnormalities and schizotypal personality in first-degree relatives. The present study is to verify the modifications of EEG power spectra in eyes-open resting state of schizophrenia and first-degree relatives, and to investigate associations between EEG band power and schizotypal personality traits in first-degree relatives of schizophrenia patients. Participant samples in this study consisted of 33 healthy normal controls, 35 unaffected first-degree relatives of schizophrenia patients and 35 schizophrenia patients. Group differences in resting EEG band power were examined via repeated-measures analysis of variance, and correlation between EEG power and schizotypal personality traits via Pearson Correlation analysis. The results showed that patients with schizophrenia exhibited increased delta, theta and alpha activity over anterior and central regions in eyes-open resting state compared with that of normal control. Gamma band power was found for the first time to be negatively correlated to schizotypal personality traits in first-degree relatives of schizophrenia patients. To conclusion, these findings suggested that low-frequency EEG activity might be neural manifestations of pathophysiological changes in the brain of schizophrenia, and gamma band activity might be an approach to measure the genetic liability of the disorder.

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.

21. ENIGMA-Relatives: The Association Between Familial Risk for Schizophrenia or Bipolar Disorder and Brain Abnormalities

Schizophrenia and bipolar disorder share genetic liability and some structural brain abnormalities are common to both conditions. Interestingly, imaging studies have indicated that there may be a converse pattern of brain abnormalities in first-degree relatives of schizophrenia patients (FDRs-SZ) and bipolar patients (FDRs-BD), with smaller volumes reported in FDRs-SZ and enlargements in FDRs-BD.

Effects of BDNF Val66Met genotype and schizophrenia familial risk on a neural functional network for cognitive control in humans.

Cognitive control represents an essential neuropsychological characteristic that allows for the rapid adaption of a changing environment by constant re-allocation of cognitive resources. This finely tuned mechanism is impaired in psychiatric disorders such as schizophrenia and contributes to cognitive deficits. Neuroimaging has highlighted the contribution of the anterior cingulate cortex (ACC) and prefrontal regions (PFC) on cognitive control and demonstrated the impact of genetic variation, as well as genetic liability for schizophrenia. In this study, we aimed to examine the influence of the functional single-nucleotide polymorphism (SNP) rs6265 of a plasticity-related neurotrophic factor gene, BDNF (Val66Met), on cognitive control. Strong evidence implicates BDNF Val66Met in neural plasticity in humans. Furthermore, several studies suggest that although the variant is not convincingly associated with schizophrenia risk, it seems to be a modifier of the clinical presentation and course of the disease. In order to clarify the underlying mechanisms using functional magnetic resonance imaging (fMRI), we studied the effects of this SNP on ACC and PFC activation, and the connectivity between these regions in a discovery sample of 85 healthy individuals and sought to replicate this effect in an independent sample of 253 individuals. Additionally, we tested the identified imaging phenotype in relation to schizophrenia familial risk in a sample of 58 unaffected first-degree relatives of schizophrenia patients. We found a significant increase in interregional connectivity between ACC and PFC in the risk-associated BDNF 66Met allele carriers. Furthermore, we replicated this effect in an independent sample and demonstrated its independence of structural confounds, as well as task specificity. A similar coupling increase was detectable in individuals with increased familial risk for schizophrenia. Our results show that a key neural circuit for cognitive control is influenced by a plasticity-related genetic variant, which may render this circuit particular susceptible to genetic and environmental risk factors for schizophrenia.

Distinct Associations of Motor Domains in Relatives of Schizophrenia Patients-Different Pathways to Motor Abnormalities in Schizophrenia?

Aberrant motor function is an integral part of schizophrenia. In fact, abnormalities are frequently found in patients, in populations at risk, and in unaffected relatives. Motor abnormalities are suspected to be relevant for the clinical outcome and could probably predict the conversion from at-risk individuals to schizophrenia. Furthermore, motor function has been argued as endophenotype of the disorder. Yet, which particular motor domain may classify as a potential endophenotype is unknown. We aimed to compare schizophrenia patients, unaffected first-degree relatives and healthy controls for different motor domains. We expected impairments in all domains in patients and in some domains in relatives. We included 43 schizophrenia patients, 34 unaffected first-degree relatives of schizophrenia patients, and 29 healthy control subjects, matched for age, gender, and education level. We compared motor function of four motor domains between the groups. The domains comprise neurological soft signs (NSS), abnormal involuntary movements (dyskinesia), Parkinsonism, and fine motor function including simple [finger tapping (FT)] and complex fine motor function, (i.e., dexterity as measured with the coin rotation test). Furthermore, we tested the association of motor function of the four domains with working memory, frontal lobe function, and nonverbal intelligence for each group separately using within-group bivariate correlations. Schizophrenia patients showed poorer motor function in all tested domains compared to healthy controls. First-degree relatives had intermediate ratings with aberrant function in two motor domains. In detail, relatives had significantly more NSS and performed poorer in the FT task than controls. In contrast, complex fine motor function was intact in relatives. Relatives did not differ from controls in dyskinesia or Parkinsonism severity. Taken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first-degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and FT. Thus, NSS and FT may be potential markers of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia.

F205. OLFACTORY IDENTIFICATION IN 7-YEAR OLD CHILDREN AT FAMILIAL RISK TO DEVELOP SCHIZOPHRENIA

BackgroundOlfactory dysfunction has repeatedly been observed in individuals diagnosed with schizophrenia. The most stable and consistent finding on the behavioral level is that of smell identification deficits. However, the nature of olfactory identification abnormalities seems to extend to structural abnormalities in the underlying neurobiology of the olfactory system. Furthermore, smell identification deficits are also documented in first-episode patients and non-psychotic first-degree relatives of schizophrenia patients. Family members of schizophrenia patients also show structural abnormalities of the olfactory system, suggesting that these may serve as an endophenotype for the development of schizophrenia.Only a few studies examined the olfactory identification ability in adolescents at-risk for schizophrenia and suggested smell identification deficits as a risk marker for schizophrenia. These studies included adolescents at clinical as well as at genetic risk for schizophrenia. None of these studies focused on children at genetic risk for schizophrenia. Therefore, we investigated the olfactory identification ability in children of parents with schizophrenia in comparison to children of parents without a psychotic disorder. As we are also interested in the specificity of the olfactory impairments to schizophrenia, we included children of parents with bipolar disorder. We hypothesize that children at genetic risk for schizophrenia would have the most severe smell identification deficits and that children of bipolar disorder patients would have less severe deficits than the at-risk for schizophrenia group but more severe than the group of children without a psychotic parent.MethodsParticipants - The olfactory identification ability was assessed in 202 children of schizophrenia patients (‘children at familial risk for schizophrenia’) in relation to that of 200 children of parents without a psychotic disorder (‘controls’). In addition, we also assessed the B-SIT in 120 children of bipolar disorder patients (‘children at familial risk for bipolar disorder’). All children were 7 years of age at the time of assessment and they were part of the Danish High Risk and Resilience Study – VIA7.Brief Smell Identification Test - The Brief Smell Identification Test (B-SIT) contains 12 items that need to be scratched and sniffed. The test has excellent reliability (> 0.80) and demonstrates agreement for abnormal olfaction comparing B-SIT with the San Diego Odor Identification Test (SDOIT). A maximum score of 12 reflects intact olfactory identification functioning. B-SIT has been conducted in patients with neurodegenerative disorders (Parkinson’s disease and Alzheimer’s disease) and can be used for individuals above 5 years of age.Statistics - We will use analysis of covariance (ANCOVA) for analysis of the B-SIT total scores with ‘diagnosis of parent’ as the independent variable and age and sex as covariates for the three groups.ResultsAnalyses will be performed within the next 3 months so can be presented in April 2018.DiscussionConclusion and discussion cannot be drawn at this time.

Clustering of Schizotypal Features in Unaffected First-Degree Relatives of Schizophrenia Patients.

Meehl conceptualized schizotypy as the phenotypic manifestations of a neural integrative defect resulting from a schizophrenia diathesis. The majority of schizotypy studies recruited subjects from the general population and revealed a multidimensional construct. This 2-phase investigation first examined the clustering of schizotypy in 194 unaffected relatives of schizophrenia patients using the Chapman Psychosis Proneness scales and then directly compared the cognitive profiles of negative schizotypal individuals and positive schizotypal individuals with schizophrenia patients and controls. In the first phase, cluster analysis categorized 194 unaffected relatives of schizophrenia patients into positive schizotypy (n = 33), negative schizotypy (n = 66), mixed schizotypy (n = 27), and low schizotypy (n = 64). Positive schizotypal participants showed more self-report pleasure experiences than negative schizotypal participants, replicating earlier cluster analytic findings. In the second phase, 27 negative schizotypal individuals, 18 positive schizotypal individuals, 19 schizophrenia patients, and 29 controls were recruited. Although the groups were matched in terms of age, gender, and IQ, they differed significantly in cognitive profiles. While schizophrenia patients exhibited the broadest cognitive impairments, negative schizotypal participants exhibited visual memory, working memory, and verbal fluency impairments, and positive schizotypal participants exhibited logical memory, visual memory, working memory, and theory-of-mind impairments. Among people with familial risk of schizophrenia, individuals exhibiting positive rather than negative schizotypal features resembled schizophrenia patients in cognitive profiles. Using the psychometric-familial method to identify schizotypy, our findings support the heterogeneity of schizotypy as well as the potential utility of the positive schizotypy dimension in genetically high-risk individuals to predict the risk of developing schizophrenia.