Non-psychotic First-degree Relatives Of Patients Research Articles

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.

Prospective memory in non-psychotic first-degree relatives of patients with schizophrenia: a meta-analysis.

Prospective memory (PM) could be impaired in the non-psychotic first-degree relatives of patients with schizophrenia. This meta-analysis systematically examined the PM of non-psychotic first-degree relatives of patients with schizophrenia. Both Chinese and English databases were systematically searched for articles from the inception of the databases through November 13, 2018. Case-control studies of PM in non-psychotic first-degree relatives of patients with schizophrenia were included in the analyses. Confidence intervals (CIs) and standardized mean differences (SMDs) were calculated utilizing the random effects model. Four studies (n=268) that compared PM performance between non-psychotic first-degree relatives of patients with schizophrenia (n=136) and healthy controls (n=132) were included. Three studies were rated as “high quality”, while the quality of evidence of the three outcomes included in this meta-analysis was moderate. Compared with the healthy controls, the non-psychotic first-degree relatives of patients with schizophrenia showed impairments in overall PM (two studies, n=127; SMD: −0.46; 95% CI=−0.82, −0.11, P=0.01; I=0%), event-based PM (EBPM) (four studies, n=268; SMD: −0.56; 95% CI=−0.80, −0.31, P<0.00001; I=0%), and time-based PM (TBPM) (four studies, n=268; SMD: −0.66; 95% CI=−0.90, −0.41, P<0.00001; I=0%). This meta-analysis demonstrated that the overall PM, EBPM, and TBPM might be impaired in the non-psychotic first-degree relatives of patients with schizophrenia.

S72. PRO-SOCIAL PROSPECTIVE MEMORY PERFORMANCE IS ASSOCIATED WITH PLASMA OXYTOCIN LEVEL IN SEXUALLY DIMORPHIC WAY IN FIRST-DEGREE RELATIVES OF SCHIZOPHRENIA

BackgroundProspective memory (PM) in real world is mostly societal and it often involves activities in which the individual has to remember to do something for others, which is also called pro-social PM. The neuropeptide oxytocin has been implicated in social cognition and social interaction in a number of studies. The aim of the present study was to investigate the correlation between pro-social PM performance and plasma oxytocin level in first-episode schizophrenic patients (FES), first-degree relatives (FDRs) of schizophrenia, and healthy controls (HCs). In addition, we also tried to explore the sexually dimorphic feature in the interactions of above-mentioned factors.MethodsForty-six FES patients, 41 non-psychotic FDRs of patients with chronic schizophrenia (unrelated to the FES group) and 54 HCs were studied. Pro-social time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance were assessed with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT). A serial of tests reflecting retrospective memory and executive functions were also administrated. Plasma oxytocin levels were determined by radioimmunoassay using a RIA kit.Results(1) There were significant differences in performance between FES, FDRs, and HCs with respect both TBPM and EBPM, even after controlling for age, sex and education level by analysis of covariance (ANCOVA). We found significant group*sex interaction only regarding TBPM (F(2, 133)=4.8, p=0.01). Female HCs performed significantly poorer than male HCs on TBPM (11.1 ± 5.5 vs 14.4 ± 4.8, t=-2.3, p=0.026). However, this sexually dimorphic trend was not seen in either FES (9.0 ± 5.1 vs 7.5 ± 5.1, t=1.0, p=0.34) or FDRs (12.3 ± 3.5 vs 11.1 ± 4.4, t=1.0, p=0.3). (2) A significant group*sex interaction was also revealed with regard to plasma oxytocin level (F(2, 134)=4.1, p=0.018). In HCs, females exhibited significantly higher plasma oxytocin level than males (62.2 ± 28.3 pg/ml vs 44.4 ± 20.9 pg/ml, t=2.5, p=0.015). But this sexually dimorphic feature did not appear in FES (58.3 ± 20.1pg/ml vs 59.6 ± 19.4 pg/ml, t=-0.2, p=0.822) or FDRs (60.4 ± 19.2 pg/ml vs 74.0 ± 46.0 pg/ml, t=-1.2, p=0.230). In addition, there was a significant difference in plasma oxytocin level between the three groups only in male. Post-hoc analyses suggest male FDRs exhibited significant higher plasma oxytocin level than male HCs. (3) After controlling age and education level, partial correlation analysis indicated higher plasma oxytocin levels to be significantly associated with higher TBPM scores in FDRs (r=0.39, p=0.015). In order to determine the origin of this correlation, we further conducted 2 separate partial correlation analyses in males and females, still with age and education level as controlled variables. The correlation between plasma oxytocin level and TBPM remained significant in male FDRs (r=0.5, p=0.021) but disappeared in female FDRs (r=0.2, p=0.434).DiscussionIn the present study, we found the pre-existing sex-specific patterns (as in HCs) of plasma oxytocin level and TBPM were substantially disrupted in FES and FDRs. Moreover, a significant association between plasma oxytocin levels and PM was only found in FDRs, and only male FDRs contribute to this significant association, suggesting oxytocin may play an important role regulating pro-social PM in FDRs in sexually dimorphic way.Longitudinal studies with larger sample size and measurement of oxytocin receptor function and genetic variations should be conducted in the future.

Prospective memory performance in non-psychotic first-degree relatives of patients with schizophrenia: a controlled study.

ObjectiveWe aimed at investigating prospective memory and its socio-demographic and neurocognitive correlates in non-psychotic, first-degree relatives (FDRs) of patients with schizophrenia compared to patients with first episode schizophrenia (FES), and healthy controls (HCs).MethodsForty-seven FES patients, 50 non-psychotic FDRs (23 offspring and 27 siblings) of patients with chronic schizophrenia (unrelated to the FES group) and 51 HCs were studied. The Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) was used to measure time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance. Other cognitive functions (involving respective memory and executive functions) were evaluated with standardized tests.ResultsAfter controlling for basic demographic characteristics including age, gender and educational level, there was a significant difference between FDRs, FES and HCs with respect to both TBPM (F(2,142) = 10.4, p<0.001) and EBPM (F(2,142) = 10.8, p<0.001). Multiple linear regression analyses revealed that lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the STROOP Word-Color Test (SWCT) contributed to TBPM impairment, while lower educational level and higher scores of the Color Trails Test-2 (CTT-2) contributed to EBPM deficit in FDRs.ConclusionsFDRs share similar but attenuated prospective memory impairments with schizophrenia patients, suggesting that prospective memory deficits may represent an endophenotype of schizophrenia.

Sleep spindle deficits in antipsychotic-naïve early course schizophrenia and in non-psychotic first-degree relatives.

Introduction: Chronic medicated patients with schizophrenia have marked reductions in sleep spindle activity and a correlated deficit in sleep-dependent memory consolidation. Using archival data, we investigated whether antipsychotic-naïve early course patients with schizophrenia and young non-psychotic first-degree relatives of patients with schizophrenia also show reduced sleep spindle activity and whether spindle activity correlates with cognitive function and symptoms.Method: Sleep spindles during Stage 2 sleep were compared in antipsychotic-naïve adults newly diagnosed with psychosis, young non-psychotic first-degree relatives of schizophrenia patients and two samples of healthy controls matched to the patients and relatives. The relations of spindle parameters with cognitive measures and symptom ratings were examined.Results: Early course schizophrenia patients showed significantly reduced spindle activity relative to healthy controls and to early course patients with other psychotic disorders. Relatives of schizophrenia patients also showed reduced spindle activity compared with controls. Reduced spindle activity correlated with measures of executive function in early course patients, positive symptoms in schizophrenia and IQ estimates across groups.Conclusions: Like chronic medicated schizophrenia patients, antipsychotic-naïve early course schizophrenia patients and young non-psychotic relatives of individuals with schizophrenia have reduced sleep spindle activity. These findings indicate that the spindle deficit is not an antipsychotic side-effect or a general feature of psychosis. Instead, the spindle deficit may predate the onset of schizophrenia, persist throughout its course and be an endophenotype that contributes to cognitive dysfunction.

Reduced subicular subdivisions of the hippocampal formation and verbal declarative memory impairments in young relatives at risk for schizophrenia

IntroductionSmaller hippocampal volumes similar to those found in schizophrenia (SZ) are frequently observed to a lesser extent in non-psychotic first-degree relatives of patients with the illness, compared to control subjects. In this study, subdivisions of the hippocampal formation and their association with verbal and visual learning and memory were assessed in persons at familial high risk (FHR) for SZ. MethodsMRI scans were acquired using a 3T Siemens scanner of young adult (ages 19–32) FHR subjects (N=46) and controls with no family history of illness (i.e., at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. Subfields of the hippocampal formation were evaluated using the van Leemput method (Van Leemput et al., 2010). Learning and memory measures were collected by standardized neurocognitive tests. ResultsControlling intracranial volume, significantly reduced left (p<0.025), and right hippocampus (p<0.024) volumes were observed in FHR subjects. Among the subfields, the left (p<0.01) and right subicula (p<0.005) were significantly reduced in the FHR group. Immediate verbal recall of stories was significantly impaired and was significantly correlated with the left and right subicula within the FHR group. ConclusionsReduced subiculum volume and its association with verbal memory refines further the association with left and right hippocampus reported in previous FHR studies of schizophrenia. Further research is needed to determine the specific genetic and environmental risk factors that may be related to hippocampal subfield alterations.

Focal and global brain measurements in siblings of patients with schizophrenia.

It remains unclear whether structural brain abnormalities in schizophrenia are caused by genetic and/or disease-related factors. Structural brain abnormalities have been found in nonpsychotic first-degree relatives of patients with schizophrenia, but results are inconclusive. This large magnetic resonance imaging study examined brain structures in patients with schizophrenia, their nonpsychotic siblings, and healthy control subjects using global and focal brain measurements. From 155 patients with schizophrenia, their 186 nonpsychotic siblings, and 122 healthy controls (including 25 sibling pairs), whole-brain scans were obtained. Segmentations of total brain, gray matter (GM), and white matter of the cerebrum, lateral and third ventricle, and cerebellum volumes were obtained. For each subject, measures of cortical thickness and GM density maps were estimated. Group differences in volumes, cortical thickness, and GM density were analyzed using Structural Equation Modeling, hence controlling for familial dependency of the data. Patients with schizophrenia, but not their nonpsychotic siblings, showed volumetric differences, cortical thinning, and reduced GM density as compared with control subjects. This study did not reveal structural brain abnormalities in nonpsychotic siblings of patients with schizophrenia compared with healthy control subjects using multiple imaging methods. Therefore, the structural brain abnormalities observed in patients with schizophrenia are for the largest part explained by disease-related factors.

Prospective memory in non-psychotic first-degree relatives of patients with schizophrenia

Although a number of studies have found prospective memory (PM) impairment in patients with schizophrenia, very little is known about the PM performance in non-psychotic relatives of these patients. The current study aimed to explore the PM performance in non-psychotic first-degree relatives of these patients. Two groups of participants (26 non-psychotic first-degree relatives of schizophrenia patients and 26 healthy comparison participants) were administered three PM tasks (time-, event-, and activity-based) and a set of neurocognitive tests. Results showed that the relatives performed significantly worse than the comparisons on most indices of the PM tasks, with a similar pattern of impairment found in other neurocognitive measures. Together with findings from previous studies, results of the current study suggest that PM may be a potential endophenotype for schizophrenia.

Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives.

There is a growing literature on brain activity in the nonpsychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients' relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients' relatives. The diversity of findings in studies of patients' relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged.

Brain Volumes in Relatives of Patients With Schizophrenia

Smaller brain volumes have consistently been found in patients with schizophrenia, particularly in gray matter and medial temporal lobe structures. Although several studies have investigated brain volumes in nonpsychotic relatives of patients with schizophrenia, results have been inconsistent. To determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients. A systematic search was conducted to identify relevant studies. Computer searches of the MEDLINE database were performed for English-language articles published before July 2005. Relevant abstracts published in 2005 were also selected. Magnetic resonance imaging studies that examined differences in brain volumes between first-degree relatives of patients with schizophrenia and healthy control subjects were obtained through computerized databases, including MEDLINE. Studies had to report sufficient data for computation of effect sizes. For each study, the Cohen d was calculated. Data extraction and calculation of the effect size were performed by 2 authors (H.B.M.B. and A.A.) who reached a consensus in cases of uncertainty and discrepancies. All analyses were performed using the random-effects model. Twenty-five studies were identified as suitable for analysis and included 1065 independent first-degree relatives of patients, 679 patients with schizophrenia, and 1100 healthy control subjects. The largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls (d = 0.31; 95% confidence interval [CI], 0.13-0.49; 9 effect sizes). Gray matter was smaller (d = 0.18; 95% CI, 0.02-0.33; 7 effect sizes) and third-ventricle volume was larger (d = 0.21; 95% CI, 0.03-0.40; 7 effect sizes) in relatives compared with healthy control subjects. Brain abnormalities are present in nonpsychotic first-degree relatives of patients with schizophrenia and are most pronounced in the hippocampus.

Abnormal response to metabolic stress in schizophrenia: marker of vulnerability or acquired sensitization?

Previous work suggests that individuals with schizophrenia display an altered homovanillic acid (HVA) response to metabolic stress. The present study replicated and extended this paradigm, including individuals with elevated genetic risk for schizophrenia. Patients with psychosis (n = 50), non-psychotic first-degree relatives of patients with psychosis (n = 51) and controls without psychosis (n = 50) underwent, in randomized order, double-blind administration of placebo and the glucose analogue 2-deoxy-D-glucose (2DG), which induces a mild, transient clinical state of glucoprivation. Plasma HVA and cortisol were assessed twice before the start of the 2DG/placebo infusion (baseline values), as well as four times post infusion. Data were analysed using multi-level random regression techniques. During the stress condition, significant increases in plasma HVA and cortisol were found. The increase in plasma HVA level during the stress condition was significantly stronger in patients than in controls, whereas this was not the case in relatives v. controls. The increase in plasma cortisol during the stress condition was significantly less in patients than controls, but no significant difference in the increase of plasma cortisol during stress was found in the comparison between relatives and controls. Patients with psychosis, but not their non-psychotic first-degree relatives, show an altered neurobiological response to metabolic stress, suggesting that this dysregulation is not a genetically transmitted vulnerability, but an illness-related effect, possibly reflecting acquired sensitization of neuroendocrine systems by repeated environmental stressors or repeated stimulation with agonistic drugs.

Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives

Previous studies of executive/attentional functions have found impairments in nonpsychotic first-degree relatives of patients with schizophrenia. The aims of this study were: (1) to replicate these findings by three laboratory measures of attention/information processing — a continuous performance test (DS-CPT), a forced-choice span of apprehension task (SPAN), and a digit symbol substitution test (DSST), and by a series of neuropsychological tests sensitive to prefrontal cortical damage — Trail Making A and B, verbal fluency (VFT), Stroop Color and Word Test (Stroop), and Wisconsin Card Sorting Test (WCST); (2) to investigate whether such executive/attentional deficits are associated with schizotypal traits assessed using the social anhedonia, physical anhedonia, perceptual aberration and magical ideation scales (Chapman, L.J., Chapman, J.P., Raulin, M.L. 1976. Scales for physical and social anhedonia. J. Abnorm. Psychol. 85, 374–382; Chapman, L.J., Chapman, J.P., Raulin, M.L., 1978. Body-image aberration in schizophrenia. J. Abnorm. Psychol. 87, 399–407; Eckblad, M., Chapman, L.J., 1983. Magical ideation as an indicator of schizotypy. J. Consult. Clin. Psychol. 51, 215–225). In both patient and relative groups, performance was significantly poorer on the DSST, VFT and Trail B, and the reaction time on the SPAN was significantly longer. These neuropsychological impairments were present as much in siblings as in parents of schizophrenic patients; age did not appear to cancel differences between the relative and control groups. In the relative group, the four scores of schizotypy were at an intermediate level between those of patient and control groups, and the social anhedonia and perceptual aberration scores tended to be significantly different between the relative and the control groups. Only two significant correlations were found between the neuropsychological performance and the measures of schizotypy.