Risk For Schizophrenia Spectrum Disorders Research Articles

Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals. CNV associations were assessed for replication in 235 SSD relatives and 583 controls, and 9,930 youth from the Adolescent Brain Cognitive Development (ABCD) Study. Known SSD- and neurodevelopmental disorder (NDD)-risk CNVs were associated with borderline intellectual functioning in SSD cases (odds ratios (OR) = 7.09 and 4.57, respectively); NDD-risk deletions were nominally associated with childhood-onset psychosis (OR = 4.34). Furthermore, deletion of genes involved in regulating gene expression during fetal brain development was associated with borderline intellectual functioning across SSD cases and non-cases (OR = 2.58), with partial replication in the ABCD cohort. Exploratory analyses of cortical morphology showed associations between fetal gene regulatory gene deletions and altered gray matter volume and cortical thickness across cohorts. Results highlight contributions of known risk CNVs to phenotypic variability in SSD and the utility of a neurodevelopmental framework for identifying mechanisms that influence phenotypic variability in SSDs, as well as the broader population, with implications for personalized medicine approaches to care.

Differences in social adjustment during adulthood between adoptees with high and low risk for schizophrenia spectrum disorders - the Finnish adoptive family study of schizophrenia.

To investigate differences in social adjustment during adulthood between adoptees with high genetic risk (HR) and low genetic risk (LR) for schizophrenia spectrum disorders. This study is a subsample of the Finnish Adoptive Family Study of Schizophrenia. The study sample consisted of 120 adoptees whose biological mothers had DSM-III-R verified schizophrenia spectrum disorders, and 142 socio-demographically matched control adoptees. The social adjustment of the adoptees was assessed using the interview-based Adult Adjustment Scale (AAS). A lower proportion of the HR adoptees (61.7%) fell into the category of good adaptation compared to LR adoptees (74.6%) (p = 0.024). In addition, the median AAS score among HR adoptees was lower compared to LR adoptees (p = 0.023). Poorer results among HR adoptees were also found regarding some individual items and the social health -domain within the AAS. The psychiatric morbidity, excluding schizophrenia spectrum disorders, was higher among HR adoptees. Psychiatric morbidity was shown to mediate the association of genetic status to total AAS, and, also to the domain of social health. According to our results, genetic susceptibility to schizophrenia is associated with weakened social adjustment during adulthood. Although our results demonstrated that psychiatric morbidity has notable effect on the association of genetic status to adult adjustment scores, the impact of other determinants, like psychosocial factors or health-related behaviour, cannot be ruled out. The comparable rearing environment provided by the adoption design in conjunction with reliable diagnostics provide new information on the relation of genetic susceptibility and social adjustment.

The Finnish Adoptive Family Study of Schizophrenia: differences in somatic diseases and conditions between adoptees with high or low genetic risk for schizophrenia spectrum disorders

Background and aims There is some evidence that offspring of patients with schizophrenia have higher somatic morbidity, which is thought to be partially due to genetic links between somatic disorders and schizophrenia. This study explored differences in somatic diseases and conditions of adoptees with high genetic risk (HR) or low genetic risk (LR) for schizophrenia spectrum disorders. Material and methods The study is part of the Finnish Adoptive Family Study of Schizophrenia. The adoptive research design used made it possible to examine how the somatic health of adoptees raised in similar adoptive families, is affected by their genetic susceptibility to schizophrenia. The study sample consisted of 373 adoptees, of whom 190 had HR and 183 had LR for schizophrenia spectrum disorders. Data on somatic morbidity were gathered from the hospital records and from the national registers of the Care Register of Health Care and the Social Insurance Institution. Results The only statistically significant difference found was in genitourinary diseases, the likelihood being twofold higher in HR adoptees compared to LR adoptees (16.8% vs. 8.2%; adj. OR = 2.13, 95% CI 1.06–4.25, p = .033). Adoptees who were female and aged over 40 had a higher prevalence of genitourinary illnesses than non-adoptees. Conclusion The significant prevalence of genitourinary diseases in adoptees at risk for schizophrenia spectrum disorders suggests that some specific somatic diseases and schizophrenia may have a shared hereditary etiology. More research is required for specific somatic diseases in study populations that can differentiate between the effects of genetic and environmental factors.

Diagnostic specificity of the child psychosis-risk screening system with a focus on the differentiation of schizophrenia spectrum disorders and neurodevelopmental disorders

BackgroundResearch on early psychosis has begun to identify psychiatric characteristics of the prodromal period of schizophrenia; however, subclinical characteristics of children in non-psychiatric fields have not been fully investigated. In our previous study, we developed the Child Psychosis-risk Screening System (CPSS).ObjectiveIn the present cross-sectional study, we attempted to identify the risk of developing psychosis in pediatric (n = 216) and psychiatric outpatients (n = 120), aged 6– 18 years, with the CPSS.MethodsAn analysis of variance of CPSS risk was performed in six diagnostic categories to examine specificity for each diagnosis. Receiver operating characteristic (ROC) curve analysis was conducted using the onset of schizophrenia spectrum as the outcome, and the discriminatory power and cut off values of the CPSS were determined. Logistic regression analysis was performed using clinical data to identify factors associated with the risk group (those at high risk of developing psychosis in the future) identified using the CPSS.ResultsThere were significant differences in risk variance among diagnostic categories (p < 0.001), especially between schizophrenia spectrum disorders (SSD) and neurodevelopmental disorders (p = 0.001). CPSS had sufficient discriminatory power for SSD diagnosis [area under the ROC curve = 0.853 (95% confidence interval: 0.774–0.931)]. The cut off value for the risk of SSD was determined to be 98.1%, achieving the best mean of the sum of sensitivity (90.9%) and specificity (84.0%). Cross-sectional logistic regression analysis showed that along with “SSD diagnosis,” “winter birth,” and “maltreatment” were factors associated with the risk group (odds ratio = 38.05 [p = 0.001], 2.30 [p = 0.016], and 0.12 [p = 0.024], respectively).ConclusionCPSS may have potential use in the early detection of psychosis and differentiation from neurodevelopmental disorders, but this study was small and further studies with larger sample sizes and longitudinal study designs are required prior to its use in routine clinical practice.

Familiality of the Intelligence Quotient in First Episode Psychosis: Is the Degree of Family Resemblance Associated With Different Profiles?

There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. The participants of the PAFIP-FAMILIAS project (129 FEP patients, 143 parents, and 97 siblings) completed the same neuropsychological battery. IQ-familiality was estimated through the Intraclass Correlation Coefficient (ICC). For each family, the intra-family resemblance score (IRS) was calculated as an index of familial similarity. The FEP patients were subgrouped and compared according to their IRS and IQ. IQ-familiality was low-moderate (ICC = 0.259). A total of 44.9% of the FEP patients had a low IRS, indicating discordancy with their family-IQ. Of these patients, those with low IQ had more schizophrenia diagnosis and a trend towards poorer premorbid adjustment in childhood and early adolescence. Whereas FEP patients with low IQ closely resembling their family-IQ were characterized by having the lowest performance in executive functions. The deviation from the familial cognitive performance may be related to a particular pathological process in SSD. Individuals with low IQ who do not reach their cognitive familial potential show difficulties in adjustment since childhood, probably influenced by environmental factors. Instead, FEP patients with high phenotypic family resemblance might have a more significant genetic burden for the disorder.

Correlations between biochemical and clinical parameters in patients at risk for schizophrenia spectrum disorders

Integrated clinical and biological approach to the early detection of attenuated psychotic symptoms within the frames of affective disorders makes it possible to detect the initial stage of the psychosis development and begin timely therapeutic intervention. The aim of the study was to evaluate the activity of glutamate, glutathione, and energy metabolism enzymes in the blood of patients who are at risk for the development of schizophrenia and to search for clinical and biological correlations. Clinical, psychometric (SOPS and HDRS-21), and biochemical examinations were made in 60 young men aged 16–25 years belonging to the risk group for the development of schizophrenia and in 21 young men from the comparison group without signs of risk of schizophrenia. The control group consisted of 25 healthy young men aged 19–25 years. The activities of cytochrome c oxidase, glutamate dehydrogenase, glutathione reductase, and glutathione-S-transferase were determined in platelets and erythrocytes. Decreased activities of platelet glutamate dehydrogenase, glutathione reductase, and glutathione-S-transferase were observed in all groups of examined patients compared with the control group. In erythrocytes, changed activities of glutathione reductase were observed only in the group of patients without attenuated psychotic symptoms, and glutathione-S-transferase — in the group of patients with attenuated symptoms. The revealed correlations between biochemical and clinical parameters differed in the examined groups of patients. The obtained results reflect the features of the pathogenic mechanisms in the schizophrenia risk group in terms of the activity levels of blood enzymes involved in glutamate, energy, and glutathione metabolism.

Psychotic disorders in young patients with Prader-Willi syndrome: A case report and literature review

IntroductionPrader-Willi syndrome (PWS) is a genetic disorder with an estimated prevalence of 1:25,000. PWS results from defective gene expression on the paternal copy of chromosome 15. In 70% of the cases it is a deletion that means that part of the paternal chromosome 15 is missing. Maternal uniparental disomy (mUPD) is present in 25% of cases. Typical clinical features of PWS are dysmorphism, hypotonia, hyperphagia, hypogonadism and developmental delay. In addition, the syndrome is accompanied by various psychiatric symptoms that are often insufficiently known within the psychiatric field. Regarding the relationship between PWS and schizophrenia spectrum disorders (SSDs), individuals with mUPD appear to have a 3 to 4 times higher risk of psychotic symptoms than those with the deletion subtype. Psychotic episodes have an atypical presentation with recurrent episodes of confusion and rapidly fluctuating psychotic and mood symptoms.ObjectivesTo describe an unusual clinical case in order to determine the management regarding clinical approach, and provide an overview of psychotic episodes in patients with PWS for the general practitioner with the most up-to-date information on workup and management.MethodsWe report a case involving a 13-year-old woman with PWS (mUPD of chromosome 15) and mild intellectual disability (IQs 59), who presented psychotic symptomatology in the form of disorganized behavior, delusional ideation, auditory hallucinations, self-referentiality and suspicion. Parents reported that these symptoms started two days prior the day of consultation. No environmentals stressors were identified and no recent treatment changes were made. Patient’s medication consists in 150 mg sertraline per day due to anxiety control and aid in emotional and behavioral regulation.ResultsGiven the diagnostic approach of a psychotic episode (PE) in a patient with PWS, it was decided to offer 0.5mg risperidone per day, in an increasing pattern until reaching a final dose of 1.25 mg per day, presenting a global remission of the psychotic symptomatology.Recommendations for patients with PWS presenting PE are based upon systematic reviews. Patients with PWS, especially mUPD subjects, are at risk for SSDs and mood disorders. Antipsychotics (APs) are the gold standard in the treatment of SSDs, and some authors have suggested that APs protect patients with previous psychotic symptoms from relapse. It is unknown whether there is a protective effect of APs in mUPD patients who have not previously exhibited psychotic signs.ConclusionsPWS represents a good example of a genetic disease with behavioral and psychiatric symptoms that may be challenging to treat with psychotropic medications. For a better understanding of psychiatric problems in adults with PWS, longitudinal studies with careful and standardized follow-up of psychiatric symptoms in PWS are necessary.Disclosure of InterestNone Declared

Juvenile depression as at-risk state for psychotic disorders

To establish the risk of psychotic disorders in juvenile depression and to study the role of negative symptoms in its formation. Seventy-four in-patients (19.6±2.3 years old), who were hospitalized for the first time in the clinic for a depressive episode, were examined. Psychometric scales HDRS, SOPS, SANS were used. The risk of manifestation of psychotic disorders was established in the presence of attenuated positive symptoms (APS) with values of at least one of the points P1, P2, P3 and P4 of the corresponding SOPS subscale more or equal to 3. The overall risk of schizophrenia spectrum disorders was established in the presence of attenuated negative symptoms (ANS) with values of at least one of the points H1-H6 of the negative SOPS subscale is more than or equal to 5. Statistical analysis was carried out using the Statistica 12 program. During the psychometric assessment of patients at admission, four groups were identified based on the presence of APS and ANS: group 1 (APS+ANS), group 2 (APS), group 3 (ANS) and a comparison group without APS/ANS. It was found that the presence of APS and ANS in the structure of depression increased its severity (U=109.0; p=0.009). Assessment of the ANS severity on the negative subscale of SOPS and on the SANS demonstrated quantitative differences with the highest representation of negative symptoms in the corresponding groups (APS+ANS and ANS) with significant differences in total scores in the comparison group (U=93.0; p=0.004 and U=85.0; p=0.002). When studying the structure of negative symptoms according to the SANS subscales, patients with APS differed in a lower degree of severity of negative symptoms only according to the «Avolition-Apathy» subscale (U=141.5; p=0.028). Patients from the comparison group, despite significant differences in other psychopathological symptoms, showed lower values only for the SANS subscales «Affective flattening» (U=112.0; p=0.02) and, to a greater extent, «Avolition-Apathy» (U=84.0; p=0.002). Based on the presence of prodromal symptoms in the structure of juvenile depression and their dynamics during therapy, one can assume not only a different degree of risk of endogenous psychoses, but also their nosological affiliation.

Deficits in adolescent social functioning, dysfunctional family processes and genetic risk for schizophrenia spectrum disorders as risk factors for later psychiatric morbidity of adoptees

Social functioning deficits during adolescence are associated with later psychiatric morbidity, particularly in offspring at high genetic risk for schizophrenia spectrum disorders. However, a shortcoming of earlier study findings is the lack of control of the impact of the family rearing environment. The study was aimed to examine the association of adoptees’ social functioning during adolescence, adoptive family functioning, and adoptees’ high (HR) or low (LR) genetic risk for schizophrenia spectrum disorders with adoptees’ later psychiatric morbidity. The present subsample from the nationwide Finnish Adoptive Family Study of Schizophrenia included 57 HR and 60 LR adoptees. Adolescent social functioning was assessed using UCLA Social Attainment Survey (UCLA SAS). Adoptive family functioning was based on Global Family Ratings (GFRs) and psychiatric disorders on DSM-III-R criteria. The results indicated that, after controlling for adoptive family functioning and genetic risk for schizophrenia spectrum disorders, deficits in peer relationships during adolescence were associated with an increased likelihood of psychiatric morbidity of adoptees. Our findings highlight social functioning deficits during adolescence, specifically in peer relationships, as plausible independent risk factors for later psychiatric disorders. These results can be utilized in identifying possible at-risk groups and targets for prevention and in developing preventive strategies.

Associations of Duration of Preadoption Out-of-home Care, Genetic Risk for Schizophrenia Spectrum Disorders and Adoptive Family Functioning with Later Psychiatric Disorders of Adoptees

The objective was to examine the impacts of duration of preadoption out-of-home care and adoptive family functioning on later psychiatric morbidity of adoptees with high (HR) and low (LR) genetic risk for schizophrenia spectrum disorders. The study uses nationwide data from the Finnish Adoptive Family Study of Schizophrenia. The study population in this substudy consisted of 43 h adoptees and 128 LR adoptees. Of these adoptees, 90 had spent 0–6 months and 81 over 6 months in preadoption out-of-home care. The family functioning of adoptive families was assessed based on Global Family Ratings and psychiatric disorders on DSM-III-R criteria. The results showed that among the adoptees with over 6 months in preadoption out-of-home care, the likelihood for psychiatric disorders was significantly increased in HR adoptees compared to LR adoptees. In adoptees with 6 months or less in preadoption out-of-home care, an increased likelihood for psychiatric disorders was found among those living in adoptive families with dysfunctional processes. These findings indicate that especially for HR children, a well-functioning early caregiving environment is crucial in terms of subsequent mental wellbeing. The results emphasize that when adoption is necessary, early placement and well-functioning adoptive family environment are beneficial to children.

The impact of traumatic childhood events on functioning in patients with schizophrenia

Introduction A history of adverse childhood experiences (ACEs) can increase the risk of schizophrenia spectrum disorders and might be related to unfavorable clinical and functional outcomes of psychosisObjectivesTo assess the relationship between the history of ACEs and functioning in stabilized patients with schizophrenia or schizoaffective disorder.MethodsWe conducted a cross-sectional, descriptive and analytical study. It was carried out on out patients with stabilized schizophrenia or schizoaffective disorder. The diagnosis of schizophrenia and schizoaffective disorder was established based on DSM-5 criteria. We used the ACEs scale to screen for traumatic events that occurred in the childhood and we used the Functional Assessment Staging Scale (FAST) to assess the patients’ ability to function and perform tasks of daily livingResultsSeventy five patients were included.The mean age was 39.81 ±9.96 years.The sex ratio was 4 .34. The mean score of ACE was 3.55 ± 2.41 and 88% of patients had experienced at least one traumatic event.The mean sore of the FAST scale was 33 ± 14.95.The total score of FAST was significantly higher in case of physical negligence in childhood (p=0.018). No correlation was found with the others ACEs.The FAST sub score of cognitive functioning correlated with the history of parents separation (p= 0.47) and physical negligence (p= 0.03). we also found that The FAST sub score of interpersonal relationships correlated with the history of emotional abuse (p=0.021)ConclusionsOur data has shown that ACEs contribute to functioning impairment in schizophrenia and schizoaffective disorder.This impairment affects mainly the cognitive functioning and the interpersonal relationshipsDisclosureNo significant relationships.

The Strengths and Difficulties Questionnaire Is of Clinical Significance Regarding Emotional and Behavioral Problems in 7-Year-Old Children With Familial Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls the Danish High Risk and Resilience Study-VIA 7; A Population-Based Cohort Study.

BackgroundChildren born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses.MethodsBy means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder (N = 202), bipolar disorder (N =120), and controls (N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS).ResultsChildren with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children.

Adolescent Social Functioning Deficits in Association With Adoptive Family Functioning and Genetic Risk for Schizophrenia Spectrum Disorders: The Finnish Adoptive Family Study of Schizophrenia.

Social functioning deficits (SFDs) during adolescence represent potential vulnerability indicators to schizophrenia spectrum disorders, but little is known about how both family environmental and genetic factors contribute to SFDs. The aim of this study was to examine the association of adoptees' adolescent social functioning with adoptive family functioning and adoptees' high (HR) or low (LR) genetic risk for schizophrenia spectrum disorders. The present subsample from the nationwide Finnish Adoptive Family Study of Schizophrenia included 88 HR and 83 LR adoptees. Adolescent social functioning was assessed using UCLA Social Attainment Survey. Assessment of adoptive family functioning was based on Global Family Ratings. Results indicated that dysfunctional family processes and high genetic risk for schizophrenia spectrum disorders contributed approximately equally to adoptees' adolescent social functioning. Our findings underscore the importance of functional family processes in adolescent social functioning, particularly in individuals at high genetic risk for severe psychiatric disorder.

The Impact of Adverse Childhood Experiences on Coping Strategies in Schizophrenia Spectrum Disorders: A Case-Control Study.

PurposeSeveral studies have shown that individuals with schizophrenia-spectrum disorders (SSD) employ ineffective coping styles. However, it remains unknown whether a history of adverse childhood experiences (AC Es), associated with a risk of SSD, contributes to these observations. Therefore, in this study, we aimed to investigate whether exposure to ACEs is associated with coping styles in subjects with SSD.Patients and MethodsWe recruited 127 inpatients with SSD and 56 healthy controls. Coping styles and ACEs were recorded using self-reports.ResultsIndividuals with SSD had significantly higher use of using avoidance coping. A history of parental antipathy, physical and sexual abuse was significantly more frequent in subjects with SSD compared to controls. Subjects with SSD had significantly higher multiplicity and severity of ACEs. Individuals with SSD and a history of parental loss had significantly higher use of avoidance coping compared to controls with and without a history of parental loss. Other characteristics of ACEs (age at first exposure, severity and multiplicity) were not associated with using specific coping strategies.ConclusionThese findings imply that higher use of using avoidance coping by individuals with SSD might be related to a history of parental loss.

Association and epistatic analysis of white matter related genes across the continuum schizophrenia and autism spectrum disorders: The joint effect of NRG1-ErbB genes

Background Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. Methods We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. Results Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. Discussion Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.

Looking at Self-Disorders through the Minnesota Multiphasic Personality Inventory (MMPI): An empirical exploration of the MMPI-derived Self-Disorder Scale

IntroductionTrait-like anomalies of subjective experience have been empirically identified as schizophrenia-specific markers of vulnerability in several clinical and genetic high-risk populations. Recently, Parnas and colleagues have identified and preliminarily explored a composite score (i.e. Self-Disorder Scale, SDO) within the Minnesota Multiphasic Personality Inventory (MMPI) that approximates such construct). SDO differs from the MMPI psychoticism scale, and includes presents items very similar to Self Disorder investigated by EASE (Examination of Anomalous Self-experience).ObjectivesThis study is a confirmatory analysis of the correspondence of Self-Disorder Scale (SDO) of the MMPI with some items of EASE, in a population of adolescents. These items are present in psychotic and in at risk mental state subjects.MethodsWe administered MMPI and EASE to 34 help seeker adolescent patients and correlate all dimensions of MMPI with EASE total score and its domains.ResultsMMPI SDO scores significantly correlated with schizophrenia-spectrum diagnosis and high-risk mental states.ConclusionsSDO is an MMPI analogous of Self Disorders and can be used as a useful screener to detect patients at potential risk for schizophrenia spectrum disorders, that could be further explored with the EASE.DisclosureNo significant relationships.

Distinguishing schizophrenia spectrum from non-spectrum disorders among young patients with first episode psychosis and at high clinical risk: The role of basic self-disturbance and neurocognition

IntroductionThe distinction between the schizophrenia spectrum and other types of disorders may be clinically relevant in terms of its predictive validity as suggested by studies showing schizophrenia spectrum patients have more unfavourable outcomes compared to other psychotic disorders. The present study aimed to investigate whether basic self-disturbances and neurocognitive processes that have been linked to psychosis risk have discriminative power for schizophrenia spectrum disorders in patients presenting with first episode psychosis (FEP) and at ultra-high risk for psychosis (UHR). Methods38 FEP patients, 48 UHR patients, and 33 healthy controls were assessed for basic self-disturbances (using the Examination of Anomalous Self-Experience, EASE, interview), source monitoring and aberrant salience (behavioural tasks to measure neurocognitive constructs). Clinical groups were divided into patients with schizophrenia spectrum disorders and those with other non-spectrum disorders and were further compared on measures controlling for symptom severity and age. ResultsBasic self-disturbances distinguished schizophrenia spectrum from non-spectrum disorders in the ‘FEP only’ sample, F = 19.76, p < 0.001, η2partial = 0.37, and also in the combined UHR/FEP sample, F = 23.56, p < 0.001, η2partial = 0.22. Additionally, some processes related to source monitoring deficits were elevated in schizophrenia spectrum disorders. In contrast, the two groups (schizophrenia spectrum vs other diagnoses) performed similarly in aberrant salience tasks. Comparable results were obtained for analyses performed with an FEP/UHR combined sample and the ‘FEP only’ sample. DiscussionBasic self-disturbances at the phenomenological level and source monitoring deficits on the neurocognitive level may be useful in identifying risk of schizophrenia spectrum disorders at the earliest clinical presentation.

Dysfunctional family functioning in high socioeconomic status families as a risk factor for the development of psychiatric disorders in adoptees: the Finnish Adoptive Family Study of Schizophrenia.

Earlier findings indicate that socioeconomic status (SES) of family associates with family functioning. This study examined the impacts of family functioning and genetic risk for schizophrenia on psychiatric morbidity of adoptees in families of high SES (HSES) and low SES (LSES). The study population is a subgroup of the Finnish Adoptive Family Study of Schizophrenia. Of the adoptees, 152 had high genetic risk for schizophrenia spectrum disorders (HR) and 151 adoptees had low risk (LR). Of the adoptees, 185 (HR = 94, LR = 91) were raised in high-SES (HSES) families and 118 (HR = 58, LR = 60) in low-SES (LSES) families. The family SES was determined by the occupational status of the main provider of the family. The functioning of adoptive families was assessed based on Global Family Ratings (GFRs) and psychiatric disorders on DSM-III-R criteria. In the HSES families, the psychiatric morbidity of the adoptees was emphasized by HR (OR = 4.28, CI 2.14-8.56) and dysfunctional family processes (OR = 6.44, CI 2.75-15.04). In the LSES families, the adoptees´ psychiatric morbidity was almost significantly increased by HR (OR = 2.10, CI 0.99-4.45), but not by dysfunctional family processes (OR = 1.33, CI 0.53-3.34). This study showed that in HSES families, dysfunctional family processes and HR for schizophrenia increased the likelihoods for the development of psychiatric disorders in adoptees. The results can be utilized in identifying risk factors in the development of psychiatric disorders and focusing preventative strategies on risk groups with acknowledging the importance of family functioning.

Associations of multidimensional temperament and character profiles with cognition and sensorimotor gating in individuals at risk for schizophrenia-spectrum disorders: preliminary findings

Cloninger’s biopsychological model for personality distinguishes between Temperament [Novelty Seeking, Harm Avoidance (HA), Reward Dependence (RD), Persistence (PS)], and Character [Self-Directedness (SD), Cooperativeness (CO), Self-Transcendence (ST)] traits. Cloninger has also described three sets of complex interactions among these traits, which can be summarized as a linked network of three cubes. Within each cube, the different combinations of the sub-dimensions formulate multidimensional profiles that describe personality more accurately compared with their individual constituents. The aim of the present study was to examine differences of these multidimensional profiles in cognitive functions and Prepulse Inhibition (PPI) in unaffected relatives of schizophrenia-spectrum patients and control individuals. We assessed 114 unaffected relatives of schizophrenia-spectrum patients and 122 controls for Temperament/Character traits, a wide range of cognitive functions, and PPI of the acoustic startle reflex. The relatives had higher Ηarm Avoidance and Self-Transcendence along with lower Reward Dependence, Persistence, Self-Directedness and Cooperativeness scores as well as lower PPI and poorer cognition compared with controls. We also found a) unequal distribution of relatives and controls in several “disadvantageous” profiles associated with the schizophrenia-spectrum, b) the Schizotypal/Disorganized, Apathetic and Fragile profiles had poorer emotional decision making and attention switching, respectively, compared with their “advantageous” counterparts and c) the Adventurous, Independent, Bossy and Resilient profiles had higher PPI compared with their counterparts. These findings further highlight the significance of personality determinants of cognitive processes and have potential implications in early intervention programs in the schizophrenia-spectrum.

High schizotypy traits are associated with reduced hippocampal resting state functional connectivity

Altered hippocampal functioning is proposed to play a critical role in the development of schizophrenia-spectrum disorders. Previous resting state functional Magnetic Resonance Imaging (rs-fMRI) studies report disrupted hippocampal connectivity in patients with psychosis and in individuals with clinical high risk, yet hippocampal connectivity has not been investigated in people with high schizotypy traits. Here we used rs-fMRI to examine hippocampal connectivity in healthy people with low (LS, n = 23) and high levels (HS, n = 22) of schizotypal traits assessed using the Schizotypy Personality Questionnaire. Using a bilateral hippocampal seed region, we examined resting state functional connectivity (RSFC) between hippocampus and striatal, thalamic and prefrontal cortex regions of interest. Compared to LS, HS participants showed lower RSFC between hippocampus and striatum and between hippocampus and thalamus. Whilst the group effect of reduced hippocampal RSFC in striatal and thalamic regions was driven by total schizotypy scores, positive schizotypy subfactor scores were significantly positively correlated with hippocampus-caudate/thalamus RSFC. Group differences in RSFC were not observed between hippocampus and prefrontal cortex. These results demonstrate that subclinical schizotypal traits are associated with altered hippocampal connectivity in striatal and thalamic regions and provide further support that hippocampal dysconnectivity confers risk for schizophrenia spectrum disorders.