Genetic High Risk For Psychosis Research Articles

Individuals with genetic high-risk for psychosis experience impaired coping styles compared with healthy controls.

Individuals with schizophrenia tend to have negative coping styles and low levels of self-esteem, but it is unclear whether coping styles and self-esteem levels are altered in people in the prodromal phase of psychosis. The study was designed to assess the role of coping style and self-esteem in the context of different phases of schizophrenia. Recurrent Schizophrenia (ReSch), first-episode schizophrenia patients (FEP), genetic-high risk for psychosis (GHR) patients, and healthy controls (HC) (40 per group) were subjected to in-person clinical interviews. The results of these interviews were then used to gauge coping style and self-esteem using the Coping Styles Questionnaire (CSQ) and the Rosenberg's Self-Esteem Scale (RSES). Data were analyzed through ANCOVAs and logistic regression analyses. The results found that positive coping style (CSQ problem-solving and CSQ seeking for help) generally decline with progression through the HC, GHR, and FEP groups, while negative coping style (CSQ fantasy, CSQ repression and CSQ self-blame) generally increase with progression through the HC, GHR, and FEP groups (except that GHR group was slightly lower than HC group in CSQ self-blame). Results for members of ReSch group were in line with those of members of the FEP group in coping style. At the level of self-esteem, the GHR group was similar to the HC group and significantly higher than the FEP group and the ReSch group. Logistic regression analyses indicated that GHR group patients exhibited increased negative coping styles (CSQ fantasy) relative to members of the HC group, but had greater Positive coping style (CSQ problem-solving) than did members of the FEP group. These findings suggest that both GHR individuals experience impaired negative coping styles which expands the understanding of the psychological characteristics of the prodromal group. Further explorations are warranted to develop optimal psychosocial interventions.

Visual P3 abnormalities in patients with first-episode schizophrenia, unaffected siblings of schizophrenia patients and individuals at ultra-high risk for psychosis

Cued version of the continuous performance test (AX-CPT) assesses sustained attention, working memory and cognitive control processes, which have been reported as impaired in schizophrenia. This study investigated visual P3 event-related potential elicited during cued CPT in patients with schizophrenia and in individuals who were at clinical or genetic high risk for psychosis to determine whether any abnormality may provide a marker of vulnerability for psychosis. Visual P3 elicited during cued CPT have not been reported in individuals at high risk for psychosis. Visual Go and NoGo P3 potentials were assessed in 34 antipsychotic-naive patients with first-episode schizophrenia (FES), 25 clinically unaffected siblings of these patients (familial high-risk for psychosis, FHR), 49 antipsychotic-naive individuals at ultra-high risk for psychosis (UHR) and 37 healthy control (HC) participants. FES patients had overall smaller P3 amplitudes than all other groups. P3 amplitude of the UHR participants was in-between the HC participants and FES patients. The anteroposterior P3 topography differed between the groups, with FES patients and FHR participants showing a more frontally distributed P3 compared with the HC participants. These findings suggest that the reduction in visual P3 amplitude may provide a vulnerability marker for psychosis in individuals who are at clinical high risk for psychosis and that a more frontally distributed visual P3 may be a marker of genetic liability for psychosis.

Identifying neurodevelopmental anomalies of white matter microstructure associated with high risk for psychosis in 22q11.2DS

Disruptions of white matter microstructure have been widely reported in schizophrenia. However, the emergence of these alterations during preclinical stages remains poorly understood. 22q11.2 Deletion Syndrome (22q11.2DS) represents a unique model to study the interplay of different risk factors that may impact neurodevelopment in premorbid psychosis. To identify the impact of genetic predisposition for psychosis on white matter development, we acquired longitudinal MRI data in 201 individuals (22q11.2DS = 101; controls = 100) aged 5–35 years with 1–3 time points and reconstructed 18 white matter tracts using TRACULA. Mixed model regression was used to characterize developmental trajectories of four diffusion measures—fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) in each tract. To disentangle the impact of additional environmental and developmental risk factors on white matter maturation, we used a multivariate approach (partial least squares (PLS) correlation) in a subset of 39 individuals with 22q11.2DS. Results revealed no divergent white matter developmental trajectories in patients with 22q11.2DS compared to controls. However, 22q11.2DS showed consistently increased FA and reduced AD, RD, and MD in most white matter tracts. PLS correlation further revealed a significant white matter-clinical risk factors relationship. These results indicate that while age-related changes are preserved in 22q11.2DS, white matter microstructure is widely disrupted, suggesting that genetic high risk for psychosis involves early occurring neurodevelopmental insults. In addition, multivariate modeling showed that clinical risk factors further impact white matter development. Together, these findings suggest that genetic, developmental, and environmental risk factors may play a cumulative role in altering normative white matter development during premorbid stages of psychosis.

Glutamatergic function in a genetic high-risk group for psychosis: A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion

Glutamatergic dysregulation is one of the leading theories regarding the pathoaetiolopy of schizophrenia. Meta-analysis of magnetic resonance spectroscopy studies in schizophrenia shows increased levels of glutamate and glutamine (Glx) in the medial frontal cortex and basal ganglia in clinical high-risk groups for psychosis and increased glutamine levels in the thalamus, but it is unclear if this is also the case in people at genetic high risk for psychosis. The aim of this study was to investigate glutamatergic function in the anterior cingulate cortex, striatum and thalamus in carriers of a genetic variant (22q11.2 deletion) associated with a high risk for psychosis. 53 volunteers (23 22q11.2 deletion carriers and 30 controls) underwent proton magnetic resonance spectroscopy imaging and neuropsychological assessments for prodromal psychotic symptoms, schizotypy, anxiety, depression and FSIQ. We did not find any difference between groups in Glx in the anterior cingulate cortex, striatum or thalamus (Glx: t(50)=-1.26, p = 0.21; U = 251, z = −0.7, p = 0.49; U = 316, z= -0.26, p = 0.79, respectively). No correlation was detected between Glx levels in any region and symptomatology or FSIQ. Our findings indicate that glutamatergic function is not altered in people at genetic high risk of psychosis due to the 22q11.2 deletion, which could suggest that this is not the mechanism underlying psychosis risk in 22q11.2 deletion carriers.

953. Reciprocal Disruptions in Cortico-thalamic and Hippocampal Connectivity in Youth at Genetic High Risk for Psychosis

953. Reciprocal Disruptions in Cortico-thalamic and Hippocampal Connectivity in Youth at Genetic High Risk for Psychosis

Childhood pegboard task predicts adult-onset psychosis-spectrum disorder among a genetic high-risk sample

Motor abnormalities have been established as a core aspect of psychosis-spectrum disorders, with numerous studies identifying deficits prior to clinical symptom presentation. Additional research is needed to pinpoint standardized motor assessments associated with psychosis-spectrum disorders prior to illness onset to enhance prediction and understanding of etiology. With a long history of findings among people with diagnosable psychosis-spectrum disorders, but little research conducted during the premorbid phase, pegboard tasks are a viable and understudied measure of premorbid for psychosis motor functioning. In the current study, examining data from the Copenhagen Perinatal Cohort, the Simultaneous Pegs Test was performed with children (n=244, aged 10–13) at genetic high risk for psychosis (n=94) and controls (n=150). Findings suggest that children who eventually developed a psychosis-spectrum disorder (n=33) were less likely to successfully complete the task within time limit relative to controls (χ2(2, N=244)=6.94, p=0.03, ϕ=0.17). Additionally, children who eventually developed a psychosis-spectrum disorder took significantly longer to complete the task relative to controls (χ2(2, N=244)=7.06, p=0.03, ϕ=0.17). As pegboard performance is thought to tap both diffuse and specific brain networks, findings suggest that pegboard tests may be useful premorbid measures of motor functioning among those on a trajectory towards a psychosis-spectrum disorder.

Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis.

Very little is known about the phenotypic expression of schizotypal traits in individuals with 22q11.2 deletion syndrome (22q11DS). The main purpose was to analyse the factorial structure, internal consistency and temporal stability of schizotypal traits, as well as their associations with prodromal states and clinical psychotic symptoms in adolescents with 22q11DS. The sample comprised 61 adolescents with 22q11DS (mean = 14.95 years, s.d. = 2.13; n = 24 at follow-up). An age-matched comparison group (n = 61, mean = 15.44 years, s.d. = 1.76) was also included. The Schizotypal Personality Questionnaire (SPQ), the Structured Interview for Prodromal Syndromes, the Positive and Negative Syndrome Scale, and the Brief Psychiatric Rating Scale were used. Adolescents with 22q11DS scored higher than the control group on the interpersonal dimension and suspiciousness subscale of the SPQ. The analysis of the internal structure of the SPQ in the sample of 22q11DS participants yielded a three-component solution (cognitive-perceptual, interpersonal, and disorganized). In addition, internal consistency coefficients ranged between 0.63 and 0.91. The schizotypal traits were highly stable across a 3.6-year interval, and ranged from 0.50 to 0.63. Self-reported schizotypal traits correlated with interview-based ratings of prodromal states and psychotic symptoms. These results indicate that the SPQ may be a valid tool to assess schizotypal traits in adolescents with 22q11DS. The identification of a reliable self-report instrument for use in individuals with learning disabilities and at genetic high risk for psychosis could be useful in clinical and research settings. Assessment of schizotypal traits may be used as a distal risk marker and in a close-in strategy in high-risk genetic samples to enhance the possibility of early detection of psychosis.

Altered asymmetry of the anterior cingulate cortex in subjects at genetic high risk for psychosis

ObjectiveMany studies have reported that patients with schizophrenia often have structural abnormalities of the anterior cingulate cortex (ACC) and that some of these seem to be of genetic origin, therefore predating the onset of illness. The present study aimed to investigate whether these alterations in the ACC are genetic in origin by comparing the morphological patterns of three groups: normal controls, subjects at genetic high risk (GHR) for psychosis, and patients with schizophrenia. The relationships between morphological variations and executive function were also investigated. MethodsThis study examined the magnetic resonance images of cingulate sulcus/paracingulate sulcus (CS/PCS) folding patterns in 222 subjects (103 normal subjects, 30 individuals at GHR, and 89 patients with schizophrenia) and evaluated differences in the morphological and asymmetrical patterns of the ACC among groups. Neurocognitive tests were then performed and differences in cognitive performance were analyzed according to morphological variation. ResultsDifferences in PCS folding were detected; the control group was significantly more likely than were other groups to show a well-developed left PCS (p=0.009) and leftward asymmetry of the PCS (p<0.001). However, neither GHR subjects (p=0.346) nor patients (p=0.784) showed this leftward asymmetry. No statistically significant differences in CS continuity were observed. A more prominent left PCS (p=0.031) and leftward PCS asymmetry (p=0.030) were both associated with higher scores on the working memory task. ConclusionThe results suggest that GHR subjects have distinct neurodevelopmental anomalies that resemble those of patients with schizophrenia even though they do not display any psychotic symptoms. Certain developmental alterations in the ACC, such as the loss of leftward sulcal asymmetry in patients with schizophrenia, might be related to genetic factors. Additionally, this morphological alteration might partly account for the impaired executive function in schizophrenia.

Effects of cannabis use on human brain structure in psychosis: a systematic review combining in vivo structural neuroimaging and post mortem studies.

It is unclear yet whether cannabis use is a moderating or causal factor contributing to grey matter alterations in schizophrenia and the development of psychotic symptoms. We therefore systematically reviewed structural brain imaging and post mortem studies addressing the effects of cannabis use on brain structure in psychosis. Studies with schizophrenia (SCZ) and first episode psychosis (FEP) patients as well as individuals at genetic (GHR) or clinical high risk for psychosis (ARMS) were included. We identified 15 structural magnetic resonance imaging (MRI) (12 cross sectional / 3 longitudinal) and 4 post mortem studies. The total number of subjects encompassed 601 schizophrenia or first episode psychosis patients, 255 individuals at clinical or genetic high risk for psychosis and 397 healthy controls. We found evidence for consistent brain structural abnormalities in cannabinoid 1 (CB1) receptor enhanced brain areas as the cingulate and prefrontal cortices and the cerebellum. As these effects have not consistently been reported in studies examining non-psychotic and healthy samples, psychosis patients and subjects at risk for psychosis might be particularly vulnerable to brain volume loss due to cannabis exposure

Cannabis and cognitive performance in psychosis: a cross-sectional study in patients with non-affective psychotic illness and their unaffected siblings

The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings. We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed. Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d -0.20 to -0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning. Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

576 Cortical Folding Patterns of Anterior Cingulate Cortex and Paracingulate Cortex in Genetic High Risk for Psychosis

576 Cortical Folding Patterns of Anterior Cingulate Cortex and Paracingulate Cortex in Genetic High Risk for Psychosis

Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR-AFF). Participants (ages 12-25) were from the Harvard Adolescent High-Risk and Hillside Family studies, including 73 HR-SCZ, 18 HR-AFF, and 84 community controls (CCs) recruited in metropolitan Boston and New York. Groups were compared on overall neurocognitive functioning, 6 domains, and 13 test scores, controlling for age, parental education, and correlated data within families. The HR-SCZ group was significantly impaired overall, while the HR-AFF group demonstrated a trend toward overall impairment. HR-SCZ subjects showed significantly lower Verbal Ability (d = .73) and Executive Functioning/Working Memory (d = .47) than CCs. HR-AFF subjects showed reduced Verbal Ability (d = .64) compared to CCs. Excluding 12 CCs with a parental history of depression (without psychosis) led to larger differences between HR and CC groups across domains. Moreover, HR-SCZ and CC group differences in Verbal Memory (d = .39) and Visual-Spatial (d = .34) became statistically significant. There were no significant differences between HR-SCZ and HR-AFF groups. Data support a modest neuropsychological deficit in persons at genetic HR for psychosis, with a broader range of deficits in HR-SCZ. Future work should assess the relationship of neurocognition to adaptive functioning and possible onset of psychosis in HR samples. Ascertainment criteria for controls may markedly influence results and interpretation of group differences.