Non-affected Siblings Research Articles

An actigraphy study investigating sleep in bipolar I patients, unaffected siblings and controls

ObjectivesDisturbances in sleep and waking patterns are highly prevalent during mood episodes in bipolar disorder. The question remains whether these disturbances persist during phases of euthymia and whether they are heritable traits of bipolar disorder. The current study investigates objective sleep measures in a large sample of bipolar I patients, non-affected siblings and controls. MethodsA total of 107 bipolar disorder I patients, 74 non-affected siblings, and 80 controls were included. Sleep was measured with actigraphy over the course of 14 days. Seven sleep parameters were analyzed for group differences and their relationship with age at onset, number of episodes and psychotic symptoms using linear mixed model analysis to account for family dependencies. ResultsPatients had a longer sleep duration and later time of sleep offset compared to the non-affected siblings but these differences were entirely attributable to differences in mood symptoms. We found no difference between patients and controls or siblings and controls when the analyses were restricted to euthymic patients. None of the bipolar illness characteristics were associated with sleep. LimitationsMedication use was not taken into account which may have influenced our findings and controls were younger compared to non-affected siblings. ConclusionsIn the largest study to date, our findings suggest that recovered bipolar I patients and their siblings do not experience clinically significant sleep disturbances. Sleep disturbances are primarily a reflection of current mood state, but are unrelated to the course of the disorder.

Grey matter volume patterns in thalamic nuclei are associated with familial risk for schizophrenia

Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder.We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients.Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder.

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study.

Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models. Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = -0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (χ2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata. Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.

Cortical and subcortical morphology deficits in cerebral gray matter in patients with schizophrenia and not affected siblings

ObjectiveExplore the basis of cortical morphometry in patients with schizophrenia and non-affected siblings by Magnetic Resonance Structural analyzing cortical thickness.MethodsTwenty-nine patients with schizophrenia treated with atypical antipsychotics and clinically stable in the last 6 months were recruited. Twenty-three not affected siblings of patients with schizophrenia and 37 healthy volunteers were recruited. Magnetic Resonance Structural was performed. FreeSurfer the brain imaging software package for analysis of Cortical Thickness is used. In the analysis of group differences in cortical thickness (CT) with the general linear model (GLM), the P-value was established in 0003 following the Bonferroni correction to control for multiple comparisons (seven regions of interest a priori in each hemisphere).ResultsSignificant differences in cortical thickness between patients and healthy controls. Differences between groups were calculated by general linear model (GLM) with age and sex as covairables (Table 1).ConclusionsIn applying the correction for multiple comparisons, differences in bilateral-lateral orbitofrontal, medial orbitofrontal-right and left temporal transverse frontal cortex are significant. Our study replicates previous findings and provides further evidence of abnormalities in the cerebral cortex, particularly in the frontal and temporal regions, being characteristic of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.AcknowledgementsL. Galindo is a Rio-Hortega-fellowship-(ISC-III; CM14/00111).

Materials and Methods.

Mice obtained for this study were products of pudgy breeding pairs from Jackson Laboratories, Bar Harbor, Maine. For the affected pudgy mice, heterozygous unaffected littermates served as controls. An affected pudgy mouse (pu/pu) can be identified at birth since it is approximately three-quarters the length of its non-affected littermates (pu/+) and has a markedly shortened, twisted tail. The mice were sacrificed by intraperitoneal injections of sodium pentobarbital. Vertebral and rib assessments were performed in 68 mice, 37 affected (pu/pu) and 31 non-affected (pu/+) age-matched siblings from the late embryo to 3 months of age. There were eight sets of births (litters) in which two or more of the sibling littermates were affected, allowing for a comparison of rib and vertebral anomalies in pudgy mice from the same mother and same pregnancy as well as with all other pudgy mice.

Growing Up with an Anxious Sibling: Psychosocial Correlates and Predictors of Sibling Relationship Quality

Relationships between young people with anxiety and their non-affected siblings are important for both individuals in the dyad, and for family dynamics throughout the lifespan; however, these relationships are not well understood. This study examined the experience of growing up with an anxious sibling from the sibling without anxiety’s point of view. We measured psychosocial factors associated with sibling relationship quality in 64 young adults with an anxious sibling. Overall, participants with anxious siblings were resilient, reporting comparable sibling relationship quality, anxiety symptoms, and psychological functioning relative to peers without anxious siblings. The contributions of caregiver burden and attributions about the causes of the sibling’s anxiety-related behavior accounted for significant variance in both sibling relationship warmth/closeness and conflict, with responsibility attributions emerging as an individual predictor of conflict. Clinical and research implications for understanding sibling relationships in the context of anxiety, and for the role of attributions in family relationships are considered.

Failure to deactivate medial prefrontal cortex in people at high risk for psychosis

Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.

Novel homozygous large deletion including the 5' part of the SPATA7 gene in a consanguineous Israeli Muslim Arab family.

To identify the genetic defect in a consanguineous Israeli Muslim Arab family with juvenile retinitis pigmentosa (RP). DNA samples were collected from the index patient, her parents, her affected sister, and two non-affected siblings. Genome-wide linkage analysis with 250K single nucleotide polymorphism (SNP) arrays was performed using DNA from the two affected patients. Owing to consanguinity in the family, we applied homozygosity mapping to identify the disease-causing gene. The candidate gene SPATA7 was screened for mutations with PCR amplifications and direct Sanger sequencing. Following high-density SNP arrays, we identified several homozygous genomic regions one of which included the SPATA7 gene. Several mutations in SPATA7 have been reported for various forms of retinal dystrophy, including Leber congenital amaurosis (LCA) and juvenile RP. PCR-based sequence content mapping, long-distance PCR amplifications, and subsequent sequencing analysis revealed a homozygous 63.4 kb large deletion that encompasses the 5' part of the SPATA7 gene including exons 1-5. The mutation showed concordant segregation with the phenotype in the family as expected for autosomal recessive mode of inheritance and is consistent with a diagnosis of juvenile RP. We report a novel homozygous large deletion in SPATA7 associated with juvenile RP in a consanguineous Israeli Muslim Arab family. This is the first larger deletion mutation reported for SPATA7.

Reactivated CD4+Tm cells of T1D patients and siblings display an exaggerated effector phenotype with heightened sensitivity to activation-induced cell death.

Dysfunction in effector memory has been proposed to contribute to autoimmunity in type 1 diabetes (T1D). Using a unique cohort of age- and sex-matched T1D patients, nonaffected siblings, and unrelated control children, we undertook a detailed analysis of proliferation, activation, effector responses, and apoptosis in reactivated CD4(+)Tm cells during T-cell receptor stimulation. Across cohorts, there was no difference in the proliferation of reactivated CD4(+)Tm cells. In T1D patients and siblings, CD4(+)Tm cells easily acquired the activated CD25(+) phenotype and effectively transitioned from a central (CD62L(+)Tcm) to an effector memory (CD62L(-)Tem) phenotype with an elevated cytokine "signature" comprising interferon (IFN)-γ and interleukin-10 in T1D patients and IFN-γ in siblings. This amplified Tem phenotype also exhibited an exaggerated immune shutdown with heightened sensitivity to activation-induced cell death and Fas-independent apoptosis. Apoptosis resulted in the elimination of one-half of the effector memory in T1D patients and siblings compared with one-third of the effector memory in control subjects. These data suggest genetic/environment-driven immune alteration in T1D patients and siblings that manifests in an exaggerated CD4(+)Tem response and shutdown by apoptosis. Further immunological studies are required to understand how this exaggerated CD4(+)Tem response fits within the pathomechanisms of T1D and how the effector memory can be modulated for disease treatment and/or prevention.

Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0-16 : 0, 16 : 0-18 : 1 and 16 : 0-18 : 2n-6, with reduced levels of 16 : 0-20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0-18 : 2n-6 and nearly half the proportion of 16 : 0-20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

Theory of Mind and attachment styles in people with psychotic disorders, their siblings, and controls.

Impaired Theory of Mind (ToM) and insecure (adult) attachment styles have been found in persons with schizophrenia as well as in their healthy siblings. ToM refers to the ability to infer mental states of self and others including beliefs and emotions. Insecure attachment is proposed to underlie impaired ToM, and comprises avoidant (discomfort with close relationships, high value of autonomy) and anxious (separation anxiety, dependency on others) attachment. Insight into the association between attachment style and ToM is clinically relevant, as it enhances our understanding and clinical approach to social dysfunction in schizophrenia. Therefore, we studied the association between insecure attachment styles and ToM in patients with schizophrenia, their siblings, and healthy controls. A total of 111 patients with a diagnosis in the schizophrenia spectrum, 106 non-affected siblings and 63 controls completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions, a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma Questionnaire-Short Form. Severity of symptoms was assessed with the Community Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale. After controlling for sex, intelligence, history of trauma and symptom severity, avoidant attachment was significantly associated with cognitive as well as with affective ToM, showing U-shaped associations, indicating better ToM performance for patients with lower or higher levels of avoidant attachment compared to medium levels. Anxious attachment in patients was associated with more problems in cognitive ToM. The results from this study support the idea that an anxious attachment style is associated with worse ToM performance in patients. Results also suggested a potential protective role of higher levels of avoidant attachment on ToM. These findings bear clinical relevance, as activation of (insecure) attachment mechanisms may affect interpersonal relations, as well as therapeutic working alliance. Further clarification is needed, especially on associations between ToM and avoidant attachment.

Neural correlates of emotion regulation in patients with schizophrenia and non-affected siblings.

BackgroundPatients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC) exhibit differences in brain activation during emotion regulation.MethodsAll subjects (n = 20 per group) performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress), in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ).ResultsThough the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas.ConclusionsGiven that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis.

Ecological assessment of executive functions in adolescents genetically at high risk for schizophrenia

ObjectiveThis study sought to examine specific executive deficits in the real-life environment among adolescents genetically at high risk for schizophrenia and understand the role of the genetic risk, victimization and family functioning, and their interaction on the deficits. MethodsThe study included 96 non-affected adolescent offspring and siblings of patients with schizophrenia in the high-risk group (HR) and 193 healthy adolescents in the healthy control group (HC), all aged between 9 and 20 years. All participants completed assessments of executive functions (EFs), victimization, and family functioning. ResultsThe multivariate analysis revealed that the HR group reported more difficulties on the Shift, Plan/Organize, and Task Completion scale than the HC group. Significant main effects were also detected for victimization level on all domains of EFs and for adaptability level on Inhibit, Working Memory, Plan, and Task Completion scales. Besides, the group×victimization level interactions were significant for Working Memory and Task Completion scales. Hierarchical regression analysis revealed that the genetic risk and victimization were predictors of executive deficits. ConclusionsThe HR group showed impaired EFs in the everyday environment. And, the genetic risk for schizophrenia and victimization may be related to executive dysfunction. Our results may provide clues about explaining the mechanisms of executive impairments in the HR group and help to identify new targets for early interventions.

Changes of lipoproteins in phenylalanine hydroxylase-deficient children during the first year of life

BackgroundInfluence of hyperphenylalaninemia on lipoproteins in early life remains unclear. MethodsWe enrolled 24 phenylalanine hydroxylase (PAH)-deficient children who were classified into a phenylketonuria (PKU) group (n=12) lacking PAH activity and a benign hyperphenylalaninemia (HPA) group (n=12) having partial PAH activity, and their 11 non-affected siblings. We measured serum total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels together with apolipoproteins for the first year of life, and compared them with those of 30 age-matched healthy controls. ResultsThe affected groups invariably had lower cholesterol levels than non-affected groups. At birth, HDL-cholesterol decrease was greatest and predominated over the LDL-cholesterol decrease: total cholesterol, 28/36% decrease to the control level in HPA/PKU; HDL-cholesterol, 33/51%; LDL-cholesterol, 20/28%. At 3months, the opposite changes were observed: total cholesterol, 16/28%; HDL-cholesterol, 13/23%; LDL-cholesterol, 16/33%. At 12months, LDL were still significantly lower in both groups (8/18%, p<.05 and .001), although HDL was significantly decreased only in the PKU group (15%, p<.05). Apolipoprotein A-I/A-II and B changed respectively in accordance with HDL-cholesterol and LDL-cholesterol changes. Despite similar phenylalanine levels, the PKU group invariably had lower cholesterol concentrations than the HPA group had. ConclusionIrrespective of phenylalanine concentrations, lipoprotein synthesis in PAH-deficient children, particularly in PKU children, was suppressed in early life.

Preliminary evidence for altered motion tracking-based hyperactivity in ADHD siblings

BackgroundIt is well-established that ADHD children have deficits in executive functions such as performance variability and sustained attention. It has been suggested that these deficits are intermediate phenotypes. Hyperactivity, a core symptom of ADHD, has not yet been explored as a potential intermediate phenotype in ADHD. The computerized Quantified behavior Test (QbTest) is a combined continuous performance and activity test that assesses hyperactivity, inattention, and impulsivity separately. The aim of the present study was to (1) investigate the utility of objectively measured motor activity as a potential intermediate phenotype in ADHD, and (2) explore intermediate phenotypes for ADHD at the factor instead of single variable level.MethodForty-five ADHD children, 22 non-affected siblings, and 45 unrelated controls with no family history of ADHD performed the QbTest. Effects of familiality as well as influences of age and gender on QbTest symptom dimensions were tested.ResultsADHD children showed the greatest impairments on all three QbTest factors, followed by their non-affected siblings, with control children showing the lowest scores. Group differences between the non-affected siblings and controls were only significant for the motion tracking-based Hyperactivity factor. Results were independent of age and gender.ConclusionHyperactivity assessed by a motion tracking system may be a useful intermediate phenotype in ADHD. Prospective research should use larger samples to further examine the QbTest factors, especially the motion tracking-based Hyperactivity factor which may be a candidate for an intermediate phenotype in ADHD.

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

BackgroundAutism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development.MethodsWe carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs.ResultsThis analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling.ConclusionsThese deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders.

WS2.5 The development, implementation and evaluation of a therapeutic group for non-affected siblings of children and young people with cystic fibrosis attending a regional paediatric CF centre

WS2.5 The development, implementation and evaluation of a therapeutic group for non-affected siblings of children and young people with cystic fibrosis attending a regional paediatric CF centre C. Anderson1, C. Dixon1, R. McKail1, E. Burrows1, R.M. Watling1, P. McCormack1, A. Pitman1, K.W. Southern1,2. 1Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom; 2University of Liverpool, Department for Women’s and Children’s Health, Liverpool, United Kingdom

Cognitive subtypes in non-affected siblings of schizophrenia patients: characteristics and profile congruency with affected family members

Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive subtypes in siblings. Cluster analyses were performed in 654 non-affected siblings, on a cognitive battery that included tests of attention, intellectual function and episodic memory. Resulting subtypes in the siblings were analyzed for cognitive, demographic and clinical characteristics and compared with those of their probands. Three sibling subtypes of cognitive function were distinguished: 'normal', 'mixed' and 'impaired'. Normal profile siblings (n = 192) were unimpaired on cognitive tests, in contrast to their proband (n = 184). Mixed profile siblings (n = 228) and their probands (n = 222) had a more similar performance pattern. Impaired profile siblings had poorer functional outcomes (n = 234) and their profile was almost identical to that of their proband (n = 223). Probands with cognitively impaired siblings could be distinguished from other schizophrenia patients by their own cognitive performance. They also had poorer clinical characteristics, including achievement of symptomatic remission. Unaffected siblings of patients with schizophrenia are heterogeneous with respect to cognitive function. The poorer the cognitive profile of the sibling, the higher the level of correspondence with the proband. The sibling's cognitive subtype was predictive for disease course in the proband. Distinguishing cognitive subtypes of unaffected siblings may be of relevance for genetic studies.

Assessment of cognition in non-affected full biological siblings of patients with schizophrenia

Background:Schizophrenia is a devastating psychotic illness which is like the most mental disorders, shows complex inheritance; the transmission of the disorder most likely involves several genes and environmental factors. It is difficult to judge whether a particular person without schizophrenia has predisposing factors for the said disease. A few studies have shown the relative sensitivity and reliability of cognitive and psychophysiological markers of brain function as the susceptibility factors for schizophrenia which may aid us to find people with an increased risk of complex disorders like schizophrenia. The present work is an exploration on cognitive impairments in unaffected siblings of patients suffering from schizophrenia with a framework to explore why a mental disorder occurs in some families but not in others.Materials and Methods:This is a single point non-invasive study of non-affected full biological siblings of patients with schizophrenia, involving administration of a battery of neuropsychological tests to assess the cognitive function in the sibling group and a control group of volunteers with no history of psychiatric illness. The control group was matched for age, gender, and education. The siblings were also divided on the basis of the type of schizophrenia their siblings (index probands) were suffering from and their results compared with each other.Results:The siblings performed significantly poorly as compared to the controls on Wisconsin card sorting test (WCST), continuous performance test (CPT), and spatial working memory test (SWMT). The comparison between the sibling subgroups based on the type of schizophrenia in the index probands did not reveal any significant difference.Conclusion:These findings suggest that there is a global impairment in the cognition of the non-affected siblings of patients of schizophrenia. Cognitive impairment might be one of the factors which will help us to hit upon people who are predisposed to develop schizophrenia in the future.

1979 – Cognitive subtypes in non-affected siblings of patients with schizophrenia: Characteristics and profile congruency with affected family member

Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their unaffected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. To investigate cognitive subtypes in siblings. Cluster analyses were performed in 654 unaffected siblings, on a cognitive battery that included tests of attention, intellectual function, and episodic memory. Resulting subtypes in the siblings were analyzed for cognitive, demographical, and clinical characteristics and compared with that of their proband. Three sibling subtypes of cognitive function were distinguished: ‘normal’, ‘mixed’, and ‘impaired’. Normal profile siblings (n= 192) were unimpaired on cognitive tests, in contrast to their proband (n= 184). Mixed profile siblings (n= 228) and their probands (n= 222) had a more similar performance pattern. Impaired profile siblings had poorer functional outcomes (n= 234), and their profile was almost identical to that of their proband (n= 223). Probands with cognitively impaired siblings could be distinguished from other schizophrenia patients by their own cognitive performance. They also had poorer clinical characteristics, including achievement of symptomatic remission. Unaffected siblings of patients with schizophrenia are heterogeneous with respect to cognitive function. The poorer the cognitive profile of the sibling, the higher the level of correspondence with the proband. The sibling's cognitive subtype was predictive for disease course in the proband. Distinguishing cognitive subtypes of unaffected siblings may be of relevance for genetic studies.