Search

Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S).A total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up.The three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p 0.001], were more likely to have failed ≥2 trials of SRIs (χ

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p 0.01), and the interaction had a negative association with global neurocognition (β = -0.093, p = 0.009), processing speed (β = -0.109, p = 0.003) and working memory (β = -0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.

BackgroundNeurocognitive deficits are considered an endophenotype for several psychiatric disorders, typically studied in unaffected first-degree relatives (FDRs). Environmental factors such as adverse childhood experiences (ACEs) may also affect neurocognition. This study examines the effect of ACEs on neurocognitive performance in FDRs of patients with severe mental illness in order to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition.MethodsThe sample consists of a total of 512 individuals composed of unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder or alcohol use disorder) and healthy controls (with no familial risk). Neurocognitive tests included processing speed (Color Trails), new learning (Auditory Verbal Learning Test), working memory (N-Back), and Theory of Mind (SOCRATIS). ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models adjusted for age, gender and education were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Total Score and the interaction (familial risk x ACE-IQ Total score).ResultsWhen all FDRs were examined as a group, the main effect of familial risk predicted poor performance in all domains of neurocognition (p ConclusionsThe impact of childhood adversity on neurocognition is moderated by familial risk of psychiatric disorders. Genetic or familial vulnerability may play a greater role in disorders such as schizophrenia and bipolar disorder, while the interaction between ACEs and family history may be more relevant in the case of disorders with greater environmental risk, such as substance use.

Background Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia). Methods Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO). Results MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03–1.11)], and this was more apparent in psychotic disorders. Conclusion MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.

Accelerator program for discovery in brain disorders using stem cells (ADBS) is an ongoing longitudinal study investigating the neurobiological aspects of five psychiatric disorders (Alzheimer’s dementia, bipolar disorder, obsessive-compulsive disorder, substance use disorder or schizophrenia) in India. The study uses several techniques (brain-imaging, psychophysics, neuropsychology, next-generation sequencing, cellular models), and in-depth clinical assessments in a longitudinal cohort from multiple-affected families. This article explores the frequency of manifestations of different psychiatric symptoms and syndromes in the participants and their relatives from the first wave of this study (August 2016 to October 2019). We screened 3,583 families and enrolled 481 families (1406 participants; 773 affected with any of the 5 disorders, and 633 relatives). The participants had a high familial prevalence with nearly a third of FDRs affected. Though similar disorders aggregated, the majority (61%) of the families had dissimilar diagnoses among members. Moreover, 15% of affected participants had two or more co-occurring syndromes. Diverse cross-cutting symptoms, unrestricted to the index syndrome, were observed in participants across diagnostic categories. The pattern and extent of co-occurrence validate the need for a transdiagnostic approach. The repository of biomaterials as well as digital datasets will serve as a valuable resource for the larger scientific community.