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Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences.

ABSTRACT: Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medication or illness chronicity. Subclinical psychotic experiences (SPEs) occur in some adolescents in the general population and increase the odds of developing psychosis in young adulthood. Investigations into the association between SPEs and MRI-measured volumes of subcortical structures in the general adolescent population would clarify the issue. Here, we collected structural MRI data in a subsample (10.5-13.3 years old) of a large-scale population-based cohort and explored subcortical volume and lateralization alterations related to SPEs (N = 203). Adolescents with SPEs demonstrated significant volumetric increases in the left hippocampus, right caudate, and right lateral ventricle, as well as a marginally significant increase in the left pallidum. Furthermore, adolescents with SPEs showed significantly more leftward laterality of pallidal volume than individuals without SPEs, which replicates our mega-analysis findings in chronic schizophrenia. We suggest that leftward asymmetries in pallidal volume already present in early adolescence may underlie the premorbid predisposition for developing psychosis in later life.

SUBMITTER: Okada N

PROVIDER: S-EPMC6261944 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences.

Okada Naohiro N Yahata Noriaki N Koshiyama Daisuke D Morita Kentaro K Sawada Kingo K Kanata Sho S Fujikawa Shinya S Sugimoto Noriko N Toriyama Rie R Masaoka Mio M Koike Shinsuke S Araki Tsuyoshi T Kano Yukiko Y Endo Kaori K Yamasaki Syudo S Ando Shuntaro S Nishida Atsushi A Hiraiwa-Hasegawa Mariko M Kasai Kiyoto K

Translational psychiatry 20181128 1

Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medicat ...[more]

PMID: 30487578

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Project description:BackgroundA large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age.MethodsThe sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ).ResultsMultivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (β = -0.220, t(79) = -2.661, p = .009, R2 = 0.494, and right (β = -0.167, t(79) = -2.043, p = .044, R2 = 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (β = .232, p = .040, R2 = 0.094, and β = -0.337, p = .022, R2 = 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]).ConclusionsMaternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.

Project description:BackgroundSchizophrenia is associated with abnormalities in neurodevelopmental processes. Furthermore, dysfunctional neural circuits involved in reward processing may be linked to the development of symptoms in schizophrenia and are predictive of long-term functional outcome. It is however unknown whether neural signatures of reward anticipation are detectable in children with high psychotic-like experiences.MethodsUsing data from the ABCD study 4.1, we defined a healthy control (N = 50) and a high psychotic-like experience (N = 50) group with a Prodromal Psychosis Syndrome (PPS) score > 3 and distress score > 6 at baseline (9-10 years) and 2nd year follow-up (11-12 years). While undergoing functional MR-imaging, all children completed the Monetary Incentive Delay task. Using the preprocessed ABCD-data, we explored whether behaviour and brain activations for reward and loss anticipation in areas underlying reward processing differed between groups and time-points. Furthermore, we investigated whether those brain activations that showed differences between the groups were predictive of later PPS scores. Additionally, we also employed computational modelling to assess response vigour.ResultsWhile response times did not differ, the computational model revealed that response vigour for salient cues was significantly lower in the high PLEs compared to controls at baseline. We also found that children with high PLEs demonstrated lower activation during reward anticipation in the anterior insula at the baseline time-point; the nucleus accumbens, the putamen, the dorsolateral (dlPFC) and the ventral medial prefrontal cortex at the 2nd year follow-up, and in the caudate at both timepoints, compared to controls. Regression analysis revealed that deactivations in the left anterior insula and left dlPFC, was predictive of later PPS scores.ConclusionThis study reveals that neural alterations during reward anticipation are detectable in children with high PLEs. These dysfunctions in neural activation patterns may serve as potential predictive biomarkers for psychosis.

Project description:Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.

Project description:The interplay between subclinical psychotic, negative, and affective symptoms has gained increased attention regarding the etiology of psychosis spectrum and other mental disorders. Importantly, research has tended to not differentiate between different subtypes of psychotic-like experiences (PLE) although they may not have the same significance for mental health. In order to gain information on the subclinical interplay between specific PLE and other symptoms as well as the significance of PLE for mental health, we investigated their specific associations in 206 healthy individuals (20-60 years, 73 females) using correlational and linear regression analyses. PLE were assessed with the Magical Ideation Questionnaire, the revised Exceptional Experiences Questionnaire, and subscales of the Schizotypal Personality Questionnaire (SPQ). The revised Symptom Checklist 90, the SPQ, and the Physical Anhedonia Scale were used to measure subclinical negative symptoms, affective symptoms, and other symptoms such as, emotional instability. As hypothesized, we found that (1) most affective symptoms and all other subclinical symptoms correlated positively with all PLE, whereas we found only partial associations between negative symptoms and PLE. Notably, (2) magical ideation and paranormal beliefs correlated negatively with physical anhedonia. In the regression analyses we found (3) similar patterns of specific positive associations between PLE and other subclinical symptoms: Suspiciousness was a specific predictor of negative-like symptoms, whereas ideas of reference, unusual perceptual experiences, and dissociative anomalous perceptions specifically predicted anxiety symptoms. Interestingly, (4) ideas of reference negatively predicted physical anhedonia. Similarly, paranormal beliefs were negatively associated with constricted affect. Moreover, odd beliefs were a negative predictor of depression, emotional instability, and unspecific symptoms. Our findings indicated that subtypes of PLE are differentially implicated in psychological functioning and should therefore not be categorized homogeneously. Moreover, paranormal beliefs, odd beliefs, and partly ideas of reference might also contribute to subjective well being in healthy individuals. Our results might serve as a starting point for longitudinal studies investigating the interplay of subtypes of subclinical symptoms along a psychopathological trajectory leading to mental disorders. Importantly, this research might help to improve therapeutic strategies for psychosis prevention.

Project description:ImportanceGenetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences.ObjectiveTo assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design.Design, setting, and participantsThis twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020.Main outcomes and measuresPrimary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences.ResultsA total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant.Conclusions and relevanceFindings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.

Dataset Information

Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences.

Publications

Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences.

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