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Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis.
Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up.
The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506).
Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.
It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.
We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.
Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.
Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.
A single nucleotide polymorphism within the CACNA1C gene (rs1006737) has been found to confer increased risk of Bipolar Disorder (BD) and has been linked to altered neuronal gating and emotional behaviour. As current models of BD suggest abnormal integration within frontolimbic networks, our aim was to explore the effect of the CACNA1C genotype on prefrontal and limbic activation.
We genotyped 90 participants from the Vulnerability to Bipolar Disorder Study comprising of 41 euthymic BD patients and 49 healthy controls. Functional magnetic resonance imaging data were obtained while participants performed a fearful versus neutral facial affect processing task.
We found a significant diagnosis by genotype interaction with BD patients homozygous for the risk allele having reduced prefrontal activation compared to the other groups.
The present findings support the hypothesis that the rs1006737 polymorphism in the CACNA1C gene confers increased risk of BD by modulating amygdala and PFC activation during emotional processing.
There is significant overlap between the cortical network involved in fearful face perception and regional abnormalities identified in patients with bipolar disorder. The primary aim of this study was to measure effective connectivity arising from Dynamic Causal Modelling (DCM) to identify differences within this network in a group of patients with bipolar disorder and controls during an affective processing task.
Functional MRI was used to record brain activations from 52 euthymic patients with bipolar disorder and 44 healthy controls engaged in a fearful versus neutral facial affect recognition task. We used Bayesian model selection to identify the best model of effective connectivity, as well as a random-effects analysis. Additionally, the endogenous connections and modulatory influences were extracted and further analyzed.
Within the network subserving fearful facial affect recognition, patients with bipolar disorder demonstrated reduced connectivity from the inferior occipital gyrus to the fusiform gyrus compared to healthy controls. Furthermore this connection when modulated by fear showed a reduction in strength in patients with bipolar disorder.
Bipolar disorder was associated with deficits early in the processing of facial affect suggesting the possibility of perceptual abnormalities being associated with the disorder.
Dr Frangou was supported by a NARSAD Independent Investigator Award
Working memory (WM) deficits are among the core cognitive abnormalities in schizophrenia. WM is subserved by widely distributed fronto-parietal networks and is undergoing robust development during adolescence. Studying the neural correlates of WM dysfunction in early-onset schizophrenia (EOS) will advance our understanding of aberrant neurodevelopmental processes in the disorder.
Nineteen patients with EOS aged 13-19 and 20 matched healthy participants underwent functional Magnetic Resonance Imaging (fMRI) as they performed a N-back verbal WM task with 3 levels of difficulty (1-back, 2-back, 3-back). Following matching for task performance, 14 patients were compared to 20 controls, using non-parametric whole brain and region of interest approaches followed by psycho-physiological interaction analysis (PPI) with seed voxel from the left parietal cluster.
Regions within the left prefrontal cortex, the left insula and bilateral anterior cingulate cortex showed reduced activation in EOS patients compared to healthy participants at the 2-back condition. In addition, ROI analysis at the same condition revealed hypoactivation in the EOS group with large effect sizes for left prefrontal and parietal regions. The PPI results revealed negative functional connectivity in the healthy participants’ group but not in EOS between left parietal and right parietal and bilateral frontal regions.
Our results support compromised function within the left prefrontal-cingulate network and left insula during the N-Back verbal WM task in patients with EOS compared to healthy participants. They also indicate the possibility of more widespread fronto-parietal network dysfunction, most noted in the left hemisphere in the disorder.
Poor decision-making is a prominent feature of Bipolar Disorder (BD) suggesting that patients may be impaired in affective aspects of complex problem solving. We examined the neural correlates of emotional learning (EL) in remitted BD patients and healthy controls (HC).
Subjects comprised three groups: (a) 11 remitted BD patients with EL (b) 11 remitted BD patients who failed to show EL and, (c) 11 HC with EL. All groups were demographically matched. Patients were also matched on clinical variables. Participants underwent functional magnetic resonance imaging (fMRI) while performing the Iowa Gambling Task. In the active condition participants relied upon EL to weigh up short-term rewards against long-term losses, in order to achieve an optimal gambling strategy. The control condition was identical to the gambling condition except for the reward/loss component. Behavioural and neural responses associated with the overall task performance were assessed.
Regardless of their performance in EL, BD patients, compared to HC, showed increased task-related activation in the insula and ventral anterior cingulate gyrus. BD patients with EL showed increased activation in left frontopolar and ventrolateral prefrontal cortices while reduced activation was noted in the same regions in BD patients who failed to show EL.
BD patients showed evidence of increased limbic activation associated with affective decision-making. Their ability to attain emotional learning was associated with increased recruitment of frontopolar and ventral prefrontal cortex regions. This finding may reflect a successful compensatory response to limbic overactivation during affective decision-making.
To examine genetic influences the anatomy of the Corpus Callosum (CC) in Bipolar Disorder (BD) by examining first-degree relatives in addition to BD patients.
We compared CCl size and shape in 180 individuals: 70 with BD, 45 of their unaffected first-degree relatives, and 75 healthy controls. The CC was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images; its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points.
Validating our previous findings, a significant global reduction in CC thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in CC size or shape from controls. Duration of illness was associated with thinning in the anterior body, whereas Lithium treatment associated with thicker anterior CC midbody.
Global and regional CC thinning is a disease related feature of BD and may not represent a marker of familial disposition.
Bipolar disorder (BD) is characterised by emotional dysregulation; abnormal emotional information processing is likely to be a component of genetic predisposition to BD.
Functional magnetic resonance imaging data was collected during an event-related facial affect recognition task (fearful, angry, sad expressions), from: 41 BDI patients, 22 of their unaffected siblings, and 51 controls. A random effects analysis was implemented using SPM5.
Patients, relative to controls had significantly:
a. reduced activation in the left inferior frontal gyrus and middle occipital gyrus and,
b. enhanced activation bilaterally in the posterior cingulate and in the left postcentral gyrus; in the temporal lobe, increased activation was seen in the hippocampus and amygdale bilaterally and in the middle and inferior temporal gyri.
Siblings, relative to controls showed significantly enhanced activation in the inferior frontal gyrus and in the parahippocampal gyrus and amydgala. Siblings relative to patients had significantly higher activation in the inferior frontal gyrus.
In BD patients there is evidence of increased limbic activation and decreased cortical efficiency during facial affect processing; increased ventral PFC activation in siblings, in the presence of increased limbic activation, may serve as a compensatory mechanism mediating resilience to disease expression.
The functional Catechol-O-methyltransferase (COMT Val 108/158 Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As estrogen may downregulate COMT, we were interested in the effect of gender, COMT genotype and the interaction between these factors on brain activations during an affective processing task. We used functional MRI to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful faces compared to neutral faces. We found a significant effect of gender on brain activations in the left amygdala and right superior temporal gyrus, where females demonstrated increased activations over males. Within these regions, female val/val carriers showed greater activity compared to met/met carriers, while male participants with a met/met allele showed greater deactivations compared to val/val carriers. There was no main effect of the COMT polymorphism, gender or genotype by gender interaction on task performance. We propose that the observed effects of gender and COMT allele on brain activations arise from differences in dopamine levels in these groups and that the gender differences and gender genotype interaction may be due to the downregulation of COMT by estrogen.
Bipolar disorder (BD) is characterised by emotional dysregulation; relatives of BD patients have a high rate of affective symptoms, and therefore abnormalities in emotional information processing are likely to be part of the genetic predisposition to BD. Examination of unaffected siblings of patients with BD can contribute to determining features of the BD phenotype which are related to familial predisposition as opposed to disease expression.
To identify the neural correlates of facial affect recognition in BD patients and their unaffected siblings.
Event-related functional magnetic resonance imaging (fMRI) EPI data was collected with a 1.5T scanner. Blood oxygenation level-dependent (BOLD) data was obtained from 41 BD type I patients, 22 of their unaffected siblings and 51 matched healthy controls during recognition of fearful, angry and sad facial expressions. A random effects analysis was implemented using SPM5 (http://www.fil.ion.ucl.ac.uk/spm).
BD patients showed reduced prefrontal cortex (PFC) activation, when compared to controls and siblings, with evidence of differentiation in location and laterality of activation maxima across different facial expressions. Regardless of valence, patients showed reduced extrastriate cortex activation. During angry faces, when compared to controls, siblings showed reduced activation in posterior cingulate gyrus, and during sad faces, enhanced activation in left ventral PFC and right parahippocampal gyrus.
Dorsolateral PFC (BA47) activation may represent a marker for genetic risk for BD. During sad faces, siblings showed greater activation of this region than HC, whilst BD patients showed reduced activation. This is consistent with previous findings implicating this region in BD.
To examine potential similarities in neural activation during the STROOP colour word test (SCWT) in patients with Bipolar Disorder (BD) and their unaffected first degree relatives of BD patients as an expression of genetic predisposition.
39 remitted BD patients were compared to 46 of their healthy relatives and to 42 controls. fMRI data were collected on a 1.5 T GE Signa MR system using a blocked periodic design and analysed in SPM5.
There was no statistically significant group difference in the behavioural performance. At the corrected cluster level threshold of p< 0.001 controls showed more activation than:
a. BD patients in the caudate, the inferior (BA 47), middle and superior frontal gyri (BA 8, 6, 46), the parietal cortices (BA 7, 40), the precuneus and occipital cortices (BA 7, 19).
b. Relatives in the caudate and cingulate cortex (BA 24, 31!). No other contrasts were significant.
These findings suggest that changes in neural activation during response inhibition may reflect genetic predisposition to BD.
Risk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders.
We reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative risks were taken from the largest available meta-analyses. We devised a method of scoring the level of exposure to each risk factor to estimate ERS. Relative risks were rounded as, due to the heterogeneity of the original studies, risk effects are imprecisely measured.
Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on simulated data showed that most of the population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.
This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses in asymptomatic individuals. This can be used as a continuous measure of liability to disease; mostly relevant to areas where the original studies took place. Its predictive ability will improve with the collection of additional, population-specific data.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
There has been extensive discussion of problems of reproducibility of research. Analytical flexibility may contribute to this, by increasing the likelihood that a reported finding represents a chance result. We explored whether analytical flexibility has increased over time, using human imaging studies of bipolar disorder and major depression. Our results indicate that the number of measures collected per study has increased over time for studies of bipolar disorder, but not for studies of major depression.
Extrasolar super-Earths likely have a far greater diversity in their atmospheric properties than giant planets. Super-Earths (planets with masses between 1 and 10 M⊕) lie in an intermediate mass regime between gas/ice giants like Neptune and rocky terrestrial planets like Earth and Venus. While some super-Earths (especially the more massive ones) may retain large amounts of hydrogen either from accretion processes or subsequent surface outgassing, other super-Earths should have atmospheres composed of predominantly heavier molecules, similar to the atmospheres of the rocky planets and moons of our Solar System. Others still may be entirely stripped of their atmospheres and remain as bare rocky cores. Of the two currently known transiting super-Earths one (GJ 1214b) likely falls into the former category with a thick atmosphere, while the other (CoRoT-7b) falls into the latter category with a very thin or nonexistent atmosphere. I review some of the theoretical work on super-Earth atmospheres, and I present methods for determining the bulk composition of a super-Earth atmosphere.
The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.
We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.
Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.
Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.
A joint model for plot yield in response to fertility trends and interplot competition is described. The
model combines the mixed model representation of a cubic smoothing spline to model fertility and
a regression model with auto-regressive terms to model competition. Estimation is based on a
generalization of residual maximum likelihood. The methods were applied to a series of 70 sugar beet
trials conducted by the Plant Breeding Institute, Cambridge, UK, and the results summarized.
The temperature dependent band structure of the pentatelluride ZrTe5 has been examined using the technique of high-resolution angle-resolved photoemission in conjunction with synchrotron radiation. Specifically, the band dispersion along the X-Γ-X high symmetry axis was mapped at 20K (T<Tc) and 170K (T>Tc), where Tc≃160K. One electron band and two hole bands within 0.5eV of the Fermi level have been identified. The dispersion of the bands indicates that they have extremely small electron and hole effective masses. The hole bands were observed to distort and shift in energy upon raising the sample temperature above Tc, indicative of a surface distortion.
A plasma enhanced chemical vapor deposition technique has been developed to grow single crystal boron carbide nanowires and nanonecklace arrays using the single precursor closo-l,2-dicarbadodecaborane (C2B10H12). Nanowire and nanonecklace growth is expedited by Fe seeding of the substrate. Using the compound Fe-(C5H5)2 as an Fe source, it has been demonstrated that the density of nanowires, as well as the types of nanostructures that grow, can be tailored by controlling the concentration of Fe deposited onto the substrate surface prior to boron carbide deposition.
Interplot competition in crop variety trials leads to biased estimates of variety differences. Modified alpha designs are proposed which aim to control competition by restricting the randomization so that adjacent varieties show similar competition effects. The designs are available in the computer program Alpha +.