White matter, cognition and psychotic-like experiences in UK Biobank.

BACKGROUND: Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs. METHODS: We investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data. RESULTS: The mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardized ß = -0.053, p = 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardized ß = 0.049, p < 0.001; standardized ß = -0.027, p = 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p = < 0.001) for gFA and 11% (p < 0.001) for gMD. CONCLUSIONS: We show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.

Experience of clinical services shapes attitudes to mental health data sharing: findings from a UK-wide survey.

BACKGROUND: Routinely-collected mental health data could deliver novel insights for mental health research. However, patients' willingness to share their mental health data remains largely unknown. We investigated factors influencing likelihood of sharing these data for research purposes amongst people with and without experience of mental illness. METHODS: We collected responses from a diverse sample of UK National Health Service (NHS) users (n = 2187) of which about half (n = 1087) had lifetime experience of mental illness. Ordinal logistic regression was used to examine the influence of demographic factors, clinical service experience, and primary mental illness on willingness to share mental health data, contrasted against physical health data. RESULTS: There was a high level of willingness to share mental (89.7%) and physical (92.8%) health data for research purposes. Higher levels of satisfaction with the NHS were associated with greater willingness to share mental health data. Furthermore, people with personal experience of mental illness were more willing than those without to share mental health data, once the variable of NHS satisfaction had been controlled for. Of the mental illnesses recorded, people with depression, obsessive-compulsive disorder (OCD), personality disorder or bipolar disorder were significantly more likely to share their mental health data than people without mental illness. CONCLUSIONS: These findings suggest that positive experiences of health services and personal experience of mental illness are associated with greater willingness to share mental health data. NHS satisfaction is a potentially modifiable factor that could foster public support for increased use of NHS mental health data in research.

The role of neuroticism in self-harm and suicidal ideation: results from two UK population-based cohorts.

BACKGROUND: Self-harm is common, debilitating and associated with completed suicide and increased all-cause mortality, but there is uncertainty about its causal risk factors, limiting risk assessment and effective management. Neuroticism is a stable personality trait associated with self-harm and suicidal ideation, and correlated with coping styles, but its value as an independent predictor of these outcomes is disputed. METHODS: Prior history of hospital-treated self-harm was obtained by record-linkage to administrative health data in Generation Scotland:Scottish Family Health Study (N = 15,798; self-harm cases = 339) and by a self-report variable in UK Biobank (N = 35,227; self-harm cases = 772). Neuroticism in both cohorts was measured using the Eysenck Personality Questionnaire-Short Form. Associations of neuroticism with self-harm were tested using multivariable regression following adjustment for age, sex, cognitive ability, educational attainment, socioeconomic deprivation, and relationship status. A subset of GS:SFHS was followed-up with suicidal ideation elicited by self-report (n = 3342, suicidal ideation cases = 158) and coping styles measured by the Coping Inventory for Stressful Situations. The relationship of neuroticism to suicidal ideation, and the role of coping style, was then investigated using multivariable logistic regression. RESULTS: Neuroticism was positively associated with hospital-associated self-harm in GS:SFHS (per EPQ-SF unit odds ratio 1.2 95% credible interval 1.1-1.2, pFDR 0.0003) and UKB (per EPQ-SF unit odds ratio 1.1 95% confidence interval 1.1-1.2, pFDR 9.8 × 10-17). Neuroticism, and the neuroticism-correlated coping style, emotion-oriented coping (EoC), were also associated with suicidal ideation in multivariable models. CONCLUSIONS: Neuroticism is an independent predictor of hospital-treated self-harm risk. Neuroticism and emotion-orientated coping styles are also predictive of suicidal ideation.

Polygenic risk score for schizophrenia and structural brain connectivity in older age: A longitudinal connectome and tractography study.

Higher polygenic risk score for schizophrenia (szPGRS) has been associated with lower cognitive function and might be a predictor of decline in brain structure in apparently healthy populations. Age-related declines in structural brain connectivity-measured using white matter diffusion MRI -are evident from cross-sectional data. Yet, it remains unclear how graph theoretical metrics of the structural connectome change over time, and whether szPGRS is associated with differences in ageing-related changes in human brain connectivity. Here, we studied a large, relatively healthy, same-year-of-birth, older age cohort over a period of 3 years (age ∼ 73 years, N = 731; age ∼76 years, N = 488). From their brain scans we derived tract-averaged fractional anisotropy (FA) and mean diffusivity (MD), and network topology properties. We investigated the cross-sectional and longitudinal associations between these structural brain variables and szPGRS. Higher szPGRS showed significant associations with longitudinal increases in MD in the splenium (ß = 0.132, pFDR = 0.040), arcuate (ß = 0.291, pFDR = 0.040), anterior thalamic radiations (ß = 0.215, pFDR = 0.040) and cingulum (ß = 0.165, pFDR = 0.040). Significant declines over time were observed in graph theory metrics for FA-weighted networks, such as mean edge weight (ß = -0.039, pFDR = 0.048) and strength (ß = -0.027, pFDR = 0.048). No significant associations were found between szPGRS and graph theory metrics. These results are consistent with the hypothesis that szPGRS confers risk for ageing-related degradation of some aspects of structural connectivity.

Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study.

BACKGROUND: Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia. METHODS: The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes. RESULTS: We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification. CONCLUSIONS: These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

Risk of transition to schizophrenia following first admission with substance-induced psychotic disorder: a population-based longitudinal cohort study.

BACKGROUND: The potential for drugs of abuse to induce acute psychotic symptoms is well recognised. However, the likelihood of transition from initial substance-induced psychotic disorder (SIPD) to chronic psychosis is much less well understood. This study investigated the rate of SIPD transition to schizophrenia (F20), the time to conversion and other possible related factors. METHODS: Using data from the Scottish Morbidity Record, we examined all patients (n = 3486) since their first admission to psychiatric hospital with a diagnosis of SIPD [International Classification of Diseases, Tenth Revision (ICD-10) codes F10-F19, with third digit five] from January 1997 to July 2012. Patients were followed until first episode of schizophrenia (ICD-10 code F20, with any third digit) or July 2012. Any change in diagnosis was noted in the follow-up period, which ranged from 1 day to 15.5 years across the groups. RESULTS: The 15.5-year cumulative hazard rate was 17.3% (s.e. = 0.007) for a diagnosis of schizophrenia. Cannabis, stimulant, opiate and multiple drug-induced psychotic disorder were all associated with similar hazard rates. The mean time to transition to a diagnosis of schizophrenia was around 13 years, although over 50% did so within 2 years and over 80% of cases presented within 5 years of SIPD diagnosis. Risk factors included male gender, younger age and longer first admission. CONCLUSIONS: SIPD episodes requiring hospital admission for more than 2 weeks are more likely to be associated with later diagnosis of schizophrenia. Follow-up periods of more than 2 years are needed to detect the majority of those individuals who will ultimately develop schizophrenia.

Childhood adversity and cortical thickness and surface area in a population at familial high risk of schizophrenia.

BACKGROUND: There is now a well-established link between childhood adversity (CA) and schizophrenia. Similar structural abnormalities to those found in schizophrenia including alterations in grey-matter volume have also been shown in those who experience CA. METHOD: We examined whether global estimates of cortical thickness or surface area were altered in those familial high-risk subjects who had been referred to a social worker or the Children's Panel compared to those who had not. RESULTS: We found that the cortical surface area of those who were referred to the Children's Panel was significantly smaller than those who had not been referred, but cortical thickness was not significantly altered. There was also an effect of social work referral on cortical surface area but not on thickness. CONCLUSIONS: Cortical surface area increases post-natally more than cortical thickness. Our findings suggest that CA can influence structural changes in the brain and it is likely to have a greater impact on cortical surface area than on cortical thickness.

Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk.

BACKGROUND: Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development. METHOD: Unaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls ('low risk', n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures. RESULTS: Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline. CONCLUSIONS: These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

Neurocognition in individuals at high familial risk of mood disorders with or without subsequent onset of depression.

BACKGROUND: Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset. METHOD: A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility. RESULTS: Reduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups. CONCLUSIONS: Reduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.

Dysfunction of emotional brain systems in individuals at high risk of mood disorder with depression and predictive features prior to illness.

BACKGROUND: Abnormalities of emotion-related brain circuitry, including cortico-thalamic-limbic regions underpin core symptoms of bipolar disorder (BD) and major depressive disorder (MDD). It is unclear whether these abnormalities relate to symptoms of the disorder, are present in unaffected relatives, or whether they can predict future illness. METHOD: The Bipolar Family Study (BFS) is a prospective longitudinal study that has examined individuals at familial risk of mood disorder and healthy controls on three occasions, 2 years apart. The current study concerns imaging data from the second assessment; 51 controls and 81 high-risk (HR) individuals performing an emotional memory task. The latter group was divided into 61 HR individuals who were well, and 20 who met diagnostic criteria for MDD. At the time of the third assessment a further 11 HR individuals (from the Well group) had developed MDD. The current analyses focused on (i) differences between groups based on diagnostic status at the time of the scan, and (ii) predictors of future illness, comparing the 11 HR individuals who became unwell after the second scanning assessment to those who remained well. RESULTS: All groups demonstrated typical emotional modulation of memory and associated brain activations. For analysis (i) the HR MDD group demonstrated increased thalamic activation v. HR Well. (ii) HR Well individuals who subsequently became ill showed increased activation of thalamus, insula and anterior cingulate compared to those who remained well. CONCLUSIONS: These findings suggest evidence for specific changes related to the presence of illness and evidence that changes in brain function in cortico-thalamic-limbic regions precede clinical illness.

Group therapy for people with bulimia nervosa: systematic review and meta-analysis.

BACKGROUND: Approximately 25% of people with bulimia nervosa (BN) who undertake therapy are treated in groups. National guidelines do not discriminate between group and individual therapy, yet each has potential advantages and disadvantages and it is unclear how their effects compare. We therefore evaluated how group therapy for BN compares with individual therapy, no treatment, or other therapies, in terms of remission from binges and binge frequency. METHOD: We performed a systematic review and meta-analysis of randomized controlled trials of group therapies for BN, following standard guidelines. RESULTS: A total of 10 studies were included. Studies were generally small with unclear risk of bias. There was low-quality evidence of a clinically relevant advantage for group cognitive behavioural therapy (CBT) over no treatment at therapy end. Remission was more likely with group CBT versus no treatment [relative risk (RR) 0.77, 95% confidence interval (CI) 0.62-0.96]. Mean weekly binges were lower with group CBT versus no treatment (2.9 v. 6.9, standardized mean difference = -0.56, 95% CI -0.96 to -0.15). One study provided low-quality evidence that group CBT was inferior compared with individual CBT to a clinically relevant degree for remission at therapy end (RR 1.24, 95% CI 1.03-1.50); there was insufficient evidence regarding frequency of binges. CONCLUSIONS: Conclusions could only be reached for CBT. Low-quality evidence suggests that group CBT is effective compared with no treatment, but there was insufficient or very limited evidence about how group and individual CBT compared. The risk of bias and imprecise estimates of effect invite further research to refine and increase confidence in these findings.

Tensor-based morphometry of cannabis use on brain structure in individuals at elevated genetic risk of schizophrenia.

BACKGROUND: Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis. METHOD: Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM). RESULTS: Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval. CONCLUSIONS: Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

Neuroticism, depressive symptoms and white-matter integrity in the Lothian Birth Cohort 1936.

BACKGROUND: Clinical depression is associated with reductions in white-matter integrity in several long tracts of the brain. The extent to which these findings are localized or related to depressive symptoms or personality traits linked to disease risk remains unclear. Method Members of the Lothian Birth Cohort 1936 (LBC936) were assessed in two waves at mean ages of 70 and 73 years. At wave 1, they underwent assessments of depressive symptoms and the personality traits of neuroticism and extraversion. Brain diffusion magnetic resonance imaging (MRI) data were obtained at the second wave and mood assessments were repeated. We tested whether depressive symptoms were related to reduced white-matter tract fractional anisotropy (FA), a measure of integrity, and then examined whether high neuroticism or low extraversion mediated this relationship. RESULTS: Six hundred and sixty-eight participants provided useable data. Bilateral uncinate fasciculus FA was significantly negatively associated with depressive symptoms at both waves (standardized ß=0.12-0.16). Higher neuroticism and lower extraversion were also significantly associated with lower uncinate FA bilaterally (standardized ß=0.09-0.15) and significantly mediated the relationship between FA and depressive symptoms. CONCLUSIONS: Trait liability to depression and depressive symptoms are associated with reduced structural connectivity in tracts connecting the prefrontal cortex with the amygdala and anterior temporal cortex. These effects suggest that frontotemporal disconnection is linked to the etiology of depression, in part through personality trait differences.

Amygdala volume in a population with special educational needs at high risk of schizophrenia.

BACKGROUND: The mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia. METHOD: Assessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated. RESULTS: Right amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p=0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p<0.05), but not in either control group. CONCLUSIONS: Intellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis.

Hippocampal function in schizophrenia and bipolar disorder.

BACKGROUND: The hippocampus plays a central role in memory formation. There is considerable evidence of abnormalities in hippocampal structure and function in schizophrenia, which may differentiate it from bipolar disorder. However, no previous studies have compared hippocampal activation in schizophrenia and bipolar disorder directly. METHOD: Fifteen patients with schizophrenia, 14 patients with bipolar disorder and 14 healthy comparison subjects took part in the study. Subjects performed a face-name pair memory task during functional magnetic resonance imaging (fMRI). Differences in blood oxygen level-dependent (BOLD) activity were determined during encoding and retrieval of the face-name pairs. RESULTS: The patient groups showed significant differences in hippocampal and prefrontal cortex (PFC) activation during face-name pair learning. During encoding, patients with schizophrenia showed decreased anterior hippocampal activation relative to subjects with bipolar disorder, whereas patients with bipolar disorder showed decreased dorsal PFC activation relative to patients with schizophrenia. During retrieval, patients with schizophrenia showed greater activation of the dorsal PFC than patients with bipolar disorder. Patients with schizophrenia also differed from healthy control subjects in the activation of several brain regions, showing impaired superior temporal cortex activation during encoding and greater dorsal PFC activation during retrieval. These effects were evident despite matched task performance. CONCLUSIONS: Patients with schizophrenia showed deficits in hippocampal activation during a memory task relative to patients with bipolar disorder. The disorders were further distinguished by differences in PFC activation. The results demonstrate that these disorders can distinguished at a group level using non-invasive neuroimaging.

Deficits in facial, body movement and vocal emotional processing in autism spectrum disorders.

BACKGROUND: Previous behavioural and neuroimaging studies of emotion processing in autistic spectrum disorder (ASD) have focused on the use of facial stimuli. To date, however, no studies have examined emotion processing in autism across a broad range of social signals. METHOD: This study addressed this issue by investigating emotion processing in a group of 23 adults with ASD and 23 age- and gender-matched controls. Recognition of basic emotions ('happiness', 'sadness', 'anger', disgust' and 'fear') was assessed from facial, body movement and vocal stimuli. The ability to make social judgements (such as approachability) from facial stimuli was also investigated. RESULTS: Significant deficits in emotion recognition were found in the ASD group relative to the control group across all stimulus domains (faces, body movements and voices). These deficits were seen across a range of emotions. The ASD group were also impaired in making social judgements compared to the control group and this correlated with impairments in basic emotion recognition. CONCLUSIONS: This study demonstrates that there are significant and broad-ranging deficits in emotion processing in ASD present across a range of stimulus domains and in the auditory and visual modality; they cannot therefore be accounted for simply in terms of impairments in face processing or in the visual modality alone. These results identify a core deficit affecting the processing of a wide range of emotional information in ASD, which contributes to the impairments in social function seen in people with this condition.

A common neural system mediating two different forms of social judgement.

BACKGROUND: A wide range of neuropsychiatric conditions, including schizophrenia and autistic spectrum disorder (ASD), are associated with impairments in social function. Previous studies have shown that individuals with schizophrenia and ASD have deficits in making a wide range of social judgements from faces, including decisions related to threat (such as judgements of approachability) and decisions not related to physical threat (such as judgements of intelligence). We have investigated healthy control participants to see whether there is a common neural system activated during such social decisions, on the basis that deficits in this system may contribute to the impairments seen in these disorders. METHOD: We investigated the neural basis of social decision making during judgements of approachability and intelligence from faces in 24 healthy participants using functional magnetic resonance imaging (fMRI). We used conjunction analysis to identify common brain regions activated during both tasks. RESULTS: Activation of the amygdala, medial prefrontal cortex, inferior prefrontal cortex and cerebellum was seen during performance of both social tasks, compared to simple gender judgements from the same stimuli. Task-specific activations were present in the dorsolateral prefrontal cortex in the intelligence task and in the inferior and middle temporal cortex in the approachability task. CONCLUSIONS: The present study identified a common network of brain regions activated during the performance of two different forms of social judgement from faces. Dysfunction of this network is likely to contribute to the broad-ranging deficits in social function seen in psychiatric disorders such as schizophrenia and ASD.

Psychotic-like experiences, polygenic risk scores for schizophrenia, and structural properties of the salience, default mode, and central-executive networks in healthy participants from UK Biobank.

Schizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We leveraged a large population-based cohort (UKBiobank, N = 3875) including information on PLEs (obtained from the Mental Health Questionnaire (MHQ); UKBiobank Category: 144; N auditory hallucinations = 55, N visual hallucinations = 79, N persecutory delusions = 16, N delusions of reference = 13), polygenic risk scores for schizophrenia (PRSSZ) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode, and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with PRSSZ and PLEs. PRSSZ was significantly associated with a latent measure of cortical thickness across the salience network (r = -0.069, p = 0.010) and PLEs showed a number of significant associations, both negative and positive, with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus, and pars orbitalis, pFDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between PRSSZ and auditory hallucinations. Generally, these results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and may predispose to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory hallucinations show structural associations with PLEs in the general population.