Unaffected First-degree Relatives 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.

Longitudinal changes in resting-state functional connectivity as markers of vulnerability or resilience in first-degree relatives of patients with bipolar disorder.

There is a significant contribution of genetic factors to the etiology of bipolar disorder (BD). Unaffected first-degree relatives of patients (UR) with BD are at increased risk of developing mental disorders and may manifest cognitive impairments and alterations in brain functional and connective dynamics, akin to their affected relatives. In this prospective longitudinal study, resting-state functional connectivity was used to explore stable and progressive markers of vulnerability i.e. abnormalities shared between UR and BD compared to healthy controls (HC) and resilience i.e. features unique to UR compared to HC and BD in full or partial remission (UR n = 72, mean age = 28.0 ± 7.2 years; HC n = 64, mean age = 30.0 ± 9.7 years; BD patients n = 91, mean age = 30.6 ± 7.7 years). Out of these, 34 UR, 48 BD, and 38 HC were investigated again following a mean time of 1.3 ± 0.4 years. At baseline, the UR showed lower connectivity values within the default mode network (DMN), frontoparietal network, and the salience network (SN) compared to HC. This connectivity pattern in UR remained stable over the follow-up period and was not present in BD, suggesting a resilience trait. The UR further demonstrated less negative connectivity between the DMN and SN compared to HC, abnormality that remained stable over time and was also present in BD, suggesting a vulnerability marker. Our findings indicate the coexistence of both vulnerability-related abnormalities in resting-state connectivity, as well as adaptive changes possibly promoting resilience to psychopathology in individual at familial risk.

Facial emotion-recognition deficits in patients with schizophrenia and unaffected first-degree relatives.

This study aimed to determine trait- and state-dependent markers of schizophrenia by investigating facial emotion-recognition (FER) deficits in remitted patients with schizophrenia and their first-degree relatives (FR). Three groups were included: the Schizophrenia group (n=66), their unaffected FR group (n=40), and healthy controls (n=50) who were matched for age, sex, and years of education. A facial-labeling task was used to examine FER deficits using the following eight standardized expressions: happy, fearful, disgusted, angry, sad, contemptuous, surprised, and neutral. There was a poorer accuracy in the recognition of sadness and anger in the Schizophrenia group as well as in contempt in both the Schizophrenia and FR groups compared with healthy controls. The response times for the recognition of contempt, sadness, and neutral emotion were delayed in the Schizophrenia group and those for fear were delayed in the Schizophrenia and FR groups compared with healthy controls. Concerning the accuracy in FER, sadness and anger can be considered state-dependent markers of remitted schizophrenia, and contempt is a trait-dependent marker of schizophrenia. Similarly, for response times in FER, contempt, sadness, and neutral emotion can be considered state-dependent markers of remitted schizophrenia, while fear is considered a trait-dependent marker of schizophrenia. These findings may contribute to the early diagnosis of schizophrenia and the development of relevant therapeutic interventions.

Cross-sectional study of patients with VCP multisystem proteinopathy 1 using dual-energy x-ray absorptiometry.

VCP multisystem proteinopathy 1 (MSP1), encompassing inclusion body myopathy (IBM), Paget's disease of bone (PDB) and frontotemporal dementia (FTD) (IBMPFD), features progressive muscle weakness, fatty infiltration, and disorganized bone structure in Pagetic bones. The aim of this study is to utilize dual-energy x-ray absorptiometry (DXA) parameters to examine it as a biomarker of muscle and bone disease in MSP1. DXA scans were obtained in 28 patients to assess body composition parameters (bone mineral density [BMD], T-score, total fat, and lean mass) across different groups: total VCP disease (n = 19), including myopathy without Paget's ("myopathy"; n = 12) and myopathy with Paget's ("Paget"; n = 7), and unaffected first-degree relatives serving as controls (n = 6). In the VCP disease group, significant declines in left hip BMD and Z-scores were noted versus the control group (p ≤ .03). The VCP disease group showed decreased whole body lean mass % (p = .04), and increased total body fat % (p = .04) compared to controls. Subgroup comparisons indicated osteopenia in 33.3% and osteoporosis in 8.3% of the myopathy group, with 14.3% exhibiting osteopenia in the Paget group. Moreover, the Paget group displayed higher lumbar L1-L4 T-score values than the myopathy group. In MSP1, DXA revealed reduced bone and lean mass, and increased fat mass. These DXA insights could aid in monitoring disease progression of muscle loss and secondary osteopenia/osteoporosis in MSP1, providing value both clinically and in clinical research.

Heart rate and heart rate variability in obsessive-compulsive disorder: Evidence from patients and unaffected first-degree relatives

Altered heart rate (HR) and heart rate variability (HRV) are common observations in psychiatric disorders. Yet, few studies have examined these cardiac measures in obsessive-compulsive disorder (OCD). The current study aimed to investigate HR and HRV, indexed by the root mean square of successive differences (RMSSD) and further time domain indices, as putative biological characteristics of OCD. Electrocardiogram was recorded during a five-minute resting state. Group differences between patients with OCD (n = 96), healthy participants (n = 112), and unaffected first-degree relatives of patients with OCD (n = 47) were analyzed. As potential moderators of group differences, we examined the influence of age and medication, respectively. As results indicated, patients with OCD showed higher HR and lower HRV compared to healthy participants. These group differences were not moderated by age. Importantly, subgroup analyses showed that only medicated patients displayed lower HRV compared to healthy individuals, while HR alterations were evident in unmedicated patients. Regarding unaffected first-degree relatives, group differences in HRV remained at trend level. Further, an age-moderated group differentiation showed that higher HRV distinguished relatives from healthy individuals in young adulthood, whereas at higher age lower HRV was indicative of relatives. Both the role of familial risk and medication in HRV alterations need further elucidation. Pending future studies, alterations in HR and potentially HRV might serve as useful indices to characterize the pathophysiology of OCD.

A composite immune and vascular stress marker in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives

AimsSubstantial evidence emphasizes immune dysregulation in patients with bipolar disorder (BD). However, whether immune dysregulation is present already in the early illness stages of BD or even precedes development of BD is largely unknown. In this study we compared immune and vascular stress markers in patients newly diagnosed with BD, their unaffected first-degree relatives (UR) and healthy control individuals (HC) and investigated the ability a composite immune and vascular stress marker to discriminate between the three groups of participants. MethodsIn a unique sample including 373 patients newly diagnosed with BD, 95 UR and 190 HC, we compared 47 immune and vascular stress markers at the baseline visit in the ongoing longitudinal Bipolar Illness Onset study. For comparison of individual immune and vascular stress markers between groups, we applied linear mixed models, whereas the composite immune and vascular stress marker was investigated using the SuperLearner ensemble-method. ResultsCompared with HC, patients newly diagnosed with BD had higher levels of the anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) and IL-10, and of the pro-inflammatory IL-6, eotaxin, monocyte chemoattractant protein-1 (MCP-1), MCP-4, Macrophage Derived Chemokine (MDC), and Thymus and Activation-Regulated Chemokine (TARC) in analyses adjusted for sex and age ranging from 26 % higher levels of IL-6 (1.26, 95 %CI: [1.12–1.43], p < 0.001, adjusted p = 0.009) and IL-10 (1.26, 95 %CI: [1.09–1.46], p = 0.002, adjusted p = 0.049), respectively, to 9 % higher eotaxin levels (1.09, 95 %CI: [1.04–1.15], p = 0.001, adjusted p = 0.024). Of these, MDC levels were 12 % higher in BD compared with UR (1.12, 95 %CI: [1.02–1.22], p = 0.001, adjusted p = 0.024). For all other markers, UR showed no difference from patients with BD or HC.Based on a data-driven model, a composite marker including all 47 immune and vascular stress markers, sex, age, BMI, smoking status, and alcohol intake, discriminated patients with BD from HC with a with an area under the receiver operating curve (AUC) of 0.76 (95 % CI: 0.75–0.77) ConclusionsHigher levels of pro-inflammatory and anti-inflammatory immune markers are present in patients newly diagnosed with BD but not in UR compared with HC, supporting immune dysregulation playing a role in the pathophysiology of BD.

Association of Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphisms with Type 1 Diabetes Risk: A South Indian Familial Study

Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D). The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population. The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population. Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study. Genotyping of VDR polymorphisms at four different loci (FokI- F/f, BsmI- B/b, TaqI- T/t, and ApaI- A/a) was assessed through the amplification refractive mutation system-polymerase chain reaction method. Serum vitamin D levels were measured in 98 T1D patients and 75 age- and sex-matched siblings. A total of 120 patients with T1D and 214 FDRs were included. Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03). The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66; p<0.03] in T1D patients conferring a susceptible association with the disease. Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57; p<0.02) among controls may confer a protective association with T1D. Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4; p=0.04) from parents to T1D patients. The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D. In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D.

P1191 Genetic determinants for smoking behaviour improve our understanding of sporadic versus familial Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) is influenced by genetic and environmental factors. The latter are often difficult to quantify and may vary over time, unlike genetics. Here, instead of looking at actual smoking behaviour, we explored the impact of genetic determinants of smoking behaviour on IBD risk in sporadic and familial IBD. Methods We calculated polygenic scores (PRS) for smoking initiation, smoking cessation, age of smoking initiation, and cigarettes per day in 2784 sporadic cases (1700 CD, 1084 UC), 682 non-IBD controls, and 60 multiplex IBD families with ≥3 affected first-degree relatives (FDR) (142 CD, 31 UC and 100 unaffected FDR). PRS were calculated for different p-value thresholds (5e-8, 1e-5, 0.01, 0.05, 0.1, 0.5 and 1), and based on effect estimates of Saunders et al (Nature 2022, table 1). Groups were compared using logistic regression. P&amp;lt;1.43e-3 was the significance threshold for Bonferroni correction. Results Sporadic IBD cases had a higher PRS for smoking initiation than controls (p=4.49e-3), which was driven by the CD cases (p=7.17e-4, fig 1A). CD cases also showed a trend for a higher PRS for cigarettes per day (p=0.026). In familial cases compared to unaffected FDR, we observed some differences in PRS for smoking, but none survived multiple testing (fig 1B). Comparing familial and sporadic cases, we found that the PRS for age at smoking initiation was higher in familial than in sporadic UC (p=9.09e-4, fig 1C). Familial CD showed a trend towards a lower PRS for age at smoking initiation (p=0.023) and smoking cessation (p=0.013) than sporadic CD. Familial CD cases are thus more at risk than sporadic CD cases as they genetically tend to start smoking younger, while the opposite is seen for UC. Also, unaffected FDR of UC families showed a lower PRS for age at smoking initiation (p=5.47e-5, fig 1D) than controls, giving them additional protection. The PRS for smoking cessation (p=3.88e-5) and cigarettes per day (p=4.47e-3) was greater in unaffected FDR of mixed families than in controls, while familial mixed cases had a lower cigarettes per day PRS than sporadic cases (p=1.59e-4). Conclusion We found that genetic determinants of smoking behaviour are associated with disease risk in familial and sporadic IBD. While CD risk overall is associated with a greater genetic propensity for smoking initiation, the higher risk in families is linked to genetic age at start of smoking. Meanwhile, unaffected FDR of these families are protected through a higher genetic propensity to stop smoking in mixed families, or to start smoking sooner in UC families, compared to population controls. This study improves our understanding of familial vs sporadic IBD, and could help stratify individuals at risk of IBD.

Socio-economic status, functioning and cognition in young versus adult patients newly diagnosed with bipolar disorder and their unaffected relatives; results from a cross-sectional study

BackgroundBipolar disorders (BD) figures on top of the World Health Organization classification of disabling disorders. It is unclear if there are socioeconomic, functioning, and cognition differences in young patients newly diagnosed with BD and whether these are different for young and adult patients newly diagnosed with BD. Understanding these differences is important for tailored treatment and support. MethodsParticipant groups included 401 patients newly diagnosed with BD, 145 of their unaffected first-degree relatives (UR) and 209 healthy control individuals (HC). First, we compared socio-economic status, functioning and cognition between young patients newly diagnosed with BD (150), UR (61) and HC (92) (15–25 years) and adult patients newly diagnosed with BD (251), UR (84) and HC (117) (>25 years), respectively.Second, within patients, we compared functioning and cognition between young and adult patients newly diagnosed with BD. ResultsIn both participant groups, patients newly diagnosed with BD, and to a lesser degree UR, had lower socio-economic status and impaired functioning and cognition compared with HC. Further, young patients newly diagnosed with BD were less functionally impaired, than adults newly diagnosed with BD, whereas cognition did not differ between groups. LimitationsApplied tools for assessments of functioning and cognition are not validated below age 18. ConclusionsOverall, lower socio-economic status and impaired functioning and cognition were found both in young and adult patients newly diagnosed with BD and their UR compared with young and adult HC, respectively. Young patients were less functionally impaired than adults, but cognition was similarly impaired.

Comparative Study of Cerebral Volumetric Variations in Patients with Schizophrenia with their Unaffected First-degree Relatives, using Magnetic Resonance Imaging Technique, a Case-control Study

Background and purpose: Schizophrenia (SZH) is a chronic mental disorder affecting the individuals` thoughts, perceptions, emotions, and behaviors. People with SZH may experience a wide range of positive, negative, and cognitive symptoms. Since there are no laboratory assays for definite SZH diagnosis, the authors aimed to identify the cerebral volumetric variations in SZH patients with the most prevalent positive symptoms as a diagnostic tool. This study selected 15 SZH patients displaying the most prevalent positive symptoms based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Assessment tools included the Mini-Mental State Examination (MMSE) for cognitive impairment, the Positive and Negative Syndrome Scale (PANSS) for symptom evaluation, and the Wechsler Intelligence Scale (WIS) for intelligence assessment. Additionally, 15 Healthy Controls (HC) without cerebral pathologies were recruited. T1w MRI images underwent analysis using Freesurfer software. Data analysis employed Mann-Whitney U and χ² tests, considering p &lt; 0.05 as significant. Results: SZH and HC groups showed no significant differences in age and gender. However, significant (p &lt; 0.05) alterations in Gray Matter (GM) volume were observed in SZH patients compared to HC. In the right hemisphere, several regions exhibited volume reduction, including the Fusiform sulcus, Rostral middle frontal gyrus, isthmus cingulate, Frontal pole, Middle temporal gyrus, Lateral occipital gyrus, and Inferior Parietal gyrus. Notably, the Precentral sulcus and Postcentral gyrus demonstrated volume acceleration. Similarly, in the left hemisphere, various regions showed volume reduction while the Paracentral gyrus indicated volume acceleration, all significant (p &lt; 0.05). Conclusion: SZH patients display significant volumetric brain changes, indicating potential for future diagnostic procedures in SZH.

Functional Alterations in Patients with Bipolar Disorder and Their Unaffected First-Degree Relatives: Insight from Genetic, Epidemiological, and Neuroimaging Data.

Bipolar disorder (BD) profoundly affects cognitive and psychosocial functioning, leading to a significant illness burden on patients and their families. Genetic factors are predominant in the onset of bipolar disorder and functional impairments. This disorder exhibits a strong family aggregation, with heritability estimates reaching up to 80%. Individuals with BD often experience impaired functioning, especially in significant areas such as physical performance, sleep, cognition, interpersonal interactions, socioeconomic status, family and marital relationships, work and school performance, well-being, and life expectancy. However, patients with different subtypes exhibit significant heterogeneity in social functioning, cognition, and creativity levels. There are notable differences in psychosocial and cognitive function in their unaffected first-degree relatives (UFR) who do not suffer but may carry susceptibility genes compared to healthy control (HC) without a family history. The observations indicate common genetic structures between BD patients and their UFR, which results in varying degrees of functional abnormalities. Therefore, this article mainly provides evidence on cognition, creativity, and psychosocial functioning in patients with BD and their UFR to provide a more comprehensive understanding of this critical topic in the field of BD. By integrating various findings, including clinical data and neuroimaging studies, our article aims to provide insights and valuable information for a deeper exploration of the pathogenesis of BD and the development of more targeted therapeutic strategies in the future.

A study of serum brain-derived neurotrophic factor level in individuals with obsessive compulsive disorder and their first-degree relatives as compared to the healthy population.

The nosological tradition in psychiatry defines diagnostic criteria for disorders based on expert consensus than objective biological markers reflecting underlying neurobiological correlates. Endophenotypes have been researched as heritable biological markers that can be quantified and defined to represent intermediate measures of a psychiatric illness. In obsessive-compulsive disorder (OCD), various putative biomarkers such as neuropsychological, neurophysiological, neuroradiological, brain-derived neurotrophic factor (BDNF), etc., have been explored. The study aimed to compare levels of serum BDNF in individuals with OCD and their unaffected first-degree relatives (FDR) with healthy controls (HC). This cross-sectional study compared serum BDNF levels in medication-free/naive individuals with OCD (n = 30) to their FDR (n = 30) and age-sex matched HC (n = 30). Intergroup comparison was done using analysis of variance (ANOVA) and post-hoc Tukey's test. Correlation analysis was conducted to find the relationship of sociodemographic and clinical correlates to serum BDNF as well as dimensional subtypes of OCD. No significant difference in BDNF levels was observed between OCD and HC (P = 0.13) but a significantly higher level was found in the FDR group compared to age-sex matched HC (P = 0.02). BDNF levels may have a complex interplay influencing the genetic inheritance and clinical manifestations of OCD. Further research is required before considering it a viable biomarker.

Visual Function and Inner Retinal Structure in Relation to Birth Factors in Autosomal Dominant Optic Atrophy.

The extreme variation in expressivity of autosomal dominant optic atrophy (ADOA) is unexplained. It is present from early childhood, why there is reason to search for pre- and perinatal risk factors for poor vision in ADOA. The process of ganglion cell pruning in the fetus is of interest because mitochondria are involved in apoptosis. We hypothesized that suboptimal mitochondrial function makes the developing retina and optic nerve vulnerable to fetal stress in ADOA. We have examined visual function and inner retinal layer structure in relation to birth parameters in ADOA. The study included 142 participants with OPA1 ADOA, 62 unaffected first-degree relatives, and 90 unrelated control subjects. Outcome measures included best-corrected visual acuity, microperimetric sensitivity, nerve fiber layer (NFL) volume, and ganglion cell layer (GCL) volume. Descriptive parameters included birth weight, maternal age at birth, birth complications, and gestational age. Analysis was made using mixed modeling. The analysis showed a significant positive association between microperimetric sensitivity and longer gestational age in ADOA (0.5 dB/week, P = 0.017). Interaction analysis showed a significant different association between microperimetric sensitivity and gestational age between participants with ADOA and the control groups (P = 0.007) and a significant difference in association between NFL volume and birth weight (P = 0.04) and gestational age (P = 0.02) between variant types. The study suggests that gestational age and birth weight may affect the expressivity of ADOA. The results support that prospectively collected pre- and perinatal data should be included in future studies of the natural history of ADOA.

Impaired mnemonic discrimination in children and adolescents at risk for schizophrenia

People with schizophrenia and their high-risk, first-degree relatives report widespread episodic memory impairments that are purportedly due, at least in part, to failures of mnemonic discrimination. Here, we examined the status of mnemonic discrimination in 36 children and adolescents (aged 11–17 years) with and without familial risk for schizophrenia by employing an object-based recognition task called the Mnemonic Similarity Task (MST). The MST assesses the ability to discriminate between studied images and unstudied images that are either perceptually similar to studied images or completely novel. We compared 16 high-risk, unaffected first-degree relatives of people with schizophrenia, bipolar disorder, and/or schizoaffective disorder to 20 low-risk, control participants. High-risk participants showed worse mnemonic discrimination than low-risk participants, with no difference in recognition memory or perceptual discrimination. Our findings demonstrate that mnemonic discrimination deficits previously observed in people with schizophrenia are also present in their young, high-risk, first-degree relatives.

Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?

Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM-first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC). Cross-sectional study design using convenient sampling was employed. We recruited FEM (n = 25), HR (n = 25), and age-matched HC (n = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory. The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test-controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test-complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001). Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.

P037 The NIHR IMID Bioresource: a descriptive analysis of the first 5000 participants

Abstract Background/Aims The NIHR Immune-mediated inflammatory diseases (IMID)-Bioresource is a recallable resource of patients with an IMID, pre-disease states and unaffected first-degree relatives. Here, we report on the recruited cohort to date, focusing on co-existent comorbidities. Methods Patients are categorised into one of three primary IMID groups: rheumatoid arthritis (RA), axial-spondyloarthropathy-psoriasis spectrum (AxSpA-PsO: AxSpA, PsO, psoriatic arthritis [PsA], reactive arthritis) and systemic autoimmune rheumatic diseases (SARDs: systemic lupus erythematosus [SLE], mixed and undifferentiated connective tissue disease). Data were collected on clinical phenotype, secondary IMIDs, medications and key co-morbidities. Results 5028 participants (4965 IMIDs, 46 pre-disease, 17 relatives) have been enrolled to the IMID-Bioresource Sept-2020-Aug-2022 from 63 UK-centres. Of those with a diagnosed IMID, RA (N = 2472) was the largest group, then AxSpA-PsO (N = 2012) and SARDs (n = 479). Two-thirds (N = 3210, 64.7%) female, median (IQR) age 57.9 (47.3-67.6) years. 1544 (62.5%) patients with primary IMID RA were seropositive. The commonest AxSpA-PsO diseases included PsO (N = 1232, 24.8%), PsA (N = 1116, 22.5%) and AxSpA (N = 467, 9.4%). SLE was the commonest SARD (N = 376, 7.6%), a third (N = 133, 35.4%) reported previous lupus nephritis. 1241 (25.0%) patients reported &amp;gt;1 IMID diagnoses. The commonest overlaps were PsO and RA (N = 108, 2.2%), PsO and AxSpA (N = 72, 1.5%) and RA and Sjögren’s syndrome (N = 65, 1.3%). 2880 (58.0%) reported minimum one (range 1-11) co-morbidity, the commonest, hypertension (N = 1201, 24.2%), depression (N = 820, 16.5%) and asthma (N = 580, 11.7%). 274 (5.5%) patients reported ischaemic heart disease, commonest in RA (N = 152, 6.2%). Interstitial lung disease was reported by 75 (1.5%) patients, again most frequent in RA (N = 48, 1.9%). Overall, 696 (14.0%) IMID patients had ≥3 co-morbidities. Oral steroid use was highest in SARD (N = 166, 34.7%). The commonest DMARD in all groups was methotrexate, followed by sulfasalazine in RA (N = 379, 15.3%) and AxSpA-PsO (N = 189, 9.4%) and mycophenolate mofetil in SARDs (N = 69, 14.4%). Overall, 2079 (41.9%) IMID patients were receiving a biological DMARD. Conclusion A high proportion of IMID patients have more than one IMID diagnoses. Significant multi-morbidity with cardiovascular, respiratory and mood disorders was observed and considerable ongoing glucocorticoid usage. The IMID-Bioresource aims to refine patient subsets based on shared immune mechanisms to ultimately, improve precision medicine and patient outcomes. Disclosure S. Dyball: Grants/research support; MRC. Other; GSK, UCB. E. Vital: None. S. Plein: None. D. McGonagle: None. A.G. Pratt: None. J. Isaacs: None. B. Griffiths: None. W. Ng: None. J. McBeth: None. C.E.M. Griffiths: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Grants/research support; GSK, Genzyme/Sanofi. Other; Eli Lilly, Roche. M.H. Buch: None. I. Bruce: Consultancies; ILTOO, AstraZeneca, Eli Lilly, GSK, Merck Serono, UCB. Grants/research support; Genzyme/Sanofi, GSK, UCB, Roche. Other; AstraZeneca, GSK, UCB.

Can neurological soft signs and neurocognitive deficits serve as a combined endophenotype for Han Chinese with bipolar disorder?

Bipolar disorder's (BD) potential endophenotypes include neurological soft signs (NSS) and neurocognitive disorders (ND). Few research, meanwhile, has coupled NSS and ND as combined endophenotypes of BD. This study intends to investigate NSS and ND and compare their differences in euthymic patients with bipolar disorder (EBP), their unaffected first-degree relatives (FDR), and healthy controls (HC). Additionally, search for potential endophenotypic subprojects of NSS and ND and construct and verify a composite endophenotypic. The subjects were all Han Chinese and consisted of 86 EBP, 81 FDR, and 81HC. Cambridge Neurological Inventory and MATRICSTM Consensus Cognitive Battery tested NSS and ND independently. All three groups displayed a trapezoidal distribution of NSS levels and cognitive abnormalities, with EBP having the most severe NSS levels and cognitive deficits, followed by FDR and HC. Among them, motor coordination in NSS and Information processing speed (IPS), Verbal learning (VL), and Working memory (WM) in neurocognitive function are consistent with the traits of the endophenotype of BD. The accuracy in differentiating EBP and HC or FDRs and HC was higher when these items were combined as predictor factors than in differentiating EBP and FDR. These results provide more evidence that motor coordination, IPS, VL, and WM may be internal characteristics of bipolar disease. When these characteristics are combined into a complex endophenotype, it may be possible to distinguish BD patients and high-risk groups from normal populations.

Associations between N-Acetylaspartate and white matter integrity in individuals with schizophrenia and unaffected relatives.

Compromised white matter has been reported in schizophrenia; however, few studies have investigated neurochemical abnormalities underlying microstructural differences. N-acetylaspartate (NAA) is used to synthesize myelin and is often reduced in persons with schizophrenia (PSZ) and their unaffected first-degree relatives (REL). Low levels of NAA could affect white matter by preventing the synthesis or repair of myelin. We used magnetic resonance spectroscopy and diffusion tensor imaging to investigate the relationship between NAA and white matter integrity in PSZ. REL were included to examine whether putative relationships are associated with symptom expression or illness liability. 52 controls, 23 REL and 25 PSZ underwent 7T proton magnetic resonance spectroscopy and/or 3T diffusion tensor imaging. NAA in the visual cortex and basal ganglia were measured and compared across groups. Diffusivity measures were compared across groups using tract-based spatial statistics and related to NAA concentrations. Visual cortex NAA was significantly reduced in PSZ compared to controls. White matter integrity did not differ between groups. Reduced cortical and subcortical NAA were associated with diffusivity measures of poor white matter microstructure. These data suggest that levels of neural NAA may be related to white matter integrity similarly across individuals with schizophrenia, those at genetic risk, and controls.

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects.

Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. We found a significant difference in olfactory identification ability among the diagnostic groups (p = 7.65 × 10-16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen's d = -0.57, p = 3.13 × 10-6) and healthy controls (d = -1.00, p = 2.19 × 10-16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls (d = -0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness (r = -0.41, p = 1.88 × 10-8) and negative symptoms (r = -0.28, p = 1.99 × 10-4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging (r = -0.24). Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.