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While it is known that patients with schizophrenia recognize facial emotions, specifically negative emotions, less accurately, little is known about how they misattribute these emotions to other emotions and whether such misattribution biases are associated with symptoms, course of the disorder, or certain cognitive functions.
Outpatients with schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 30) performed a computerised Facial Emotion Attribution Test and Wisconsin Card Sorting Test (WCST). Patients were also rated on the Positive and Negative Syndrome Scale (PANSS).
Patients were poor at recognizing fearful and angry emotions and attributed fear to angry and angry to neutral expressions. Fear-as-anger misattributions were predicted independently by a longer duration of illness and WCST perseverative errors.
The findings show a bias towards misattributing fearful and angry facial emotions. The propensity for fear-as-anger misattribution biases increases as the length of time that the disorder is experienced increases and a more rigid style of information processing is used. This, at least in part, may be perpetuated by subtle fearfulness expressed by others while interacting with people with schizophrenia.
Bipolar Disorder (BD) is associated with structural and functional abnormalities in prefrontal and limbic areas implicated in emotional processing. Lamotrigine (LTG) has been shown to improve depressive features in BD although its mechanism of therapeutic action is not known. The current study examined the possibility that LTG may improve functional activation within the neural circuitry involved in emotional processing.
We used functional Magnetic Resonance Imaging to examine changes in patterns of brain activation in 12 stable BD patients (a) compared to healthy controls when medication free and (b) after 12 weeks of Lamotrigine monotherapy whilst performing a sad facial affect recognition task on both occasions.
At baseline, compared to controls, BD patients showed overactivity in response to sad facial affect recognition in temporal lobe regions and under-activity in dorsal medial and right ventrolateral PFC and the dorsal cingulate gyrus. After 4 weeks of LTG monotherapy, patients showed reduced activation in temporal regions and increased neural response in dorsomedial and ventrolateral prefrontal regions.
This preliminary evidence suggests the possibility that LTG may enhance functional activation within prefrontal regions responsible for emotional self-regulation.
Declaration of interest
This study was supported by an unrestricted grant from GlaxoSmithKline
Bipolar Disorder (BD) is associated with impairment in emotional self-regulation and verbal working memory. Lamotrigine (LTG) is effective in the clinical management of BD.
To investigate whether treatment with LTG is coupled with altered function within neural circuits subserving emotional processing and verbal working memory, in a BDI sample.
Functional Magnetic Resonance Imaging (MRI) was used to explore blood oxygenation level-dependent (BOLD) response across the whole brain in 12 stable BDI patients at baseline and following 12 weeks of LGT monotherapy. Stimuli were presented in a block-design while individuals performed a verbal working memory (N-back sequential letter) task and in an event-related fashion during an angry facial affect recognition task. Data was acquired using a 1.5-Tesla MRI scanner and analysed using SPM2. Group activation maps were generated for each task and for the drug-free and post-medication condition. A threshold of p < 0.001 was used. Effect of LGT on brain activation during tasks was explored using a random-effects, within-group comparison.
In both tasks, LGT monotherapy was associated with increased BOLD signal when compared to baseline in a number of brain regions, mostly within the prefrontal cortex and cingulate gyrus. All foci of increased activation with LTG monotherapy were observed within cortical regions normally engaged in verbal working memory and facial affect processing.
LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation.
This study was supported by an unrestricted GlaxoSmithKline grant.
Dysfunctional impulsivity reflects ‘recklessness without deliberation and evaluation of consequences’ and has negative consequences whereas functional impulsivity reflects ‘rapid responding to situational demands in order to maximise one's circumstances’ and often has positive consequences (1).
To examine the functional brain basis of dysfunctional impulsivity in healthy people and in people with schizophrenia.
Thirteen healthy controls and 21 schizophrenia patients (10/21 with serious repetitive violence) underwent fMRI during a Go/ NoGo task. Dysfunctional impulsivity was indexed using the Impulsiveness subscale and functional impulsivity using the Venturesomeness subscale of the Impulsiveness-Venturesomeness-Empathy questionnaire (2).
Violent patients had elevated Impulsiveness scores relative to non-violent patients and controls. Impulsiveness did not correlate significantly with task performance in healthy controls or patients. Impulsiveness, but not Venturesomeness, scores correlated during the NoGO condition with lower activity in the anterior cingulate (AC) in controls, and lower inferior temporal and hippocampal activity in patients.
These findings accord with previously reported associations between reduced hippocampal volume and dysfunctional impulsivity in schizophrenia (3) and, combined with our earlier observations of reduced AC activation during a working memory task in violent antisocial individuals (4), suggest that the influence of dysfunctional impulsivity in antisocial and criminal behaviour is mediated via deficient (inhibitory) functions of the AC and hippocampus.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
Not much is known at present about the behavioural and sensory profiles of children with avoidant/restrictive food intake disorder (ARFID), the newest addition to the eating disorder diagnostic category in DSM-V. Our aims were to examine eating difficulties, behavioural problems and sensory hypersensitivity in ARFID children, relative to typically developing children with no reported feeding, mental or physical health problems, as well as children with autistic spectrum disorders (ASD; typically associated with a high prevalence of eating problems) or Picky Eating (PE).
Four hundred and eighty-six parents of children with ARFID (n = 29), ASD (n = 56), PE (n = 143) or no reported difficulties (n = 259) completed (online) the Behavioral Pediatric Feeding Assessment Scale, the Child Eating Behaviour Questionnaire, Strengths and Difficulties Questionnaire, and the Sensory Experiences Questionnaire about the children.
The ARFID, ASD and PE groups had eating difficulties, behavioural problems and sensory hypersensitivity, relative to the typically developing group, and differed significantly on only some of the dimensions assessed. Specifically, the ARFID group had the lowest food-responsiveness and differed significantly from the PE and typically developing (but not from ASD) groups while the ASD group had significantly greater behavioural problems and social and non-social sensitivity than all other groups.
Notable overlap in eating difficulties, behavioural problems and sensory profiles of children with ARFID, ASD or PE, with more severe aberrations in ARFID (food-responsiveness) and ASD (hypersensitivity and social problems) on specific dime7nsions, argue for a dimensional approach to improve therapy and management of children with these disorders.
As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
Molecular dynamics simulations were utilized to determine the oxygen anion diffusivity in pure ceria (CeO2) and doped ceria MxCe1-xO2-0.5x (M=Gd, Sm and Pr) with varying level of dopant concentration from 5-30% (x = 0.05-0.3). Doping with Gd showed an improvement in oxygen anion diffusivity value by two order of magnitude (D = 4.67x10-8 cm2/s at 1173 K) as compared to the undoped ceria (D = 1.33x10-10 cm2/s at 1173 K). 10% of doping level was estimated as the optimum concentration of all the dopants at which all of the doped ceria materials showed maximum diffusivity of oxygen anion. Among the three dopants studied, Pr was observed to show maximum diffusivity of oxygen anion in the temperature range of 773-1173 K of simulations.
CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.
Systemic inflammation may play a role in the development of idiopathic fatigue, that is, fatigue not explained by infections or diagnosed chronic illness, but this relationship has never been investigated in community studies including the entire adult age span. We examine the association of the inflammatory marker C-reactive protein (CRP) and fatigue assessed annually in a 3-year outcome period for UK adults aged 16–98.
Multilevel models were used to track fatigue 7, 19, and 31 months after CRP measurement, in 10 606 UK individuals. Models accounted for baseline fatigue, demographics, health conditions diagnosed at baseline and during follow-up, adiposity, and psychological distress. Sensitivity analyses considered factors including smoking, sub-clinical disease (blood pressure, anaemia, glycated haemoglobin), medications, ethnicity, and alcohol consumption.
Fatigue and CRP increased with age, and women had higher values than men. CRP was associated with future self-reported fatigue, but only for the oldest participants. Thus, in those aged 61–98 years, high CRP (>3 mg/L) independently predicted greater fatigue 7, 19, and 31 months after CRP measurement [odds ratio for new-onset fatigue after 7 months: 1.88, 95% confidence interval (CI) 1.21–2.92; 19 months: 2.25, CI 1.46–3.49; 31 months: 1.65, CI 1.07–2.54]. No significant longitudinal associations were seen for younger participants.
Our findings support previously described CRP–fatigue associations in older individuals. However, there are clear age modifications in these associations, which may reflect a contribution of unmeasured sub-clinical disease of limited relevance to younger individuals. Further work is necessary to clarify intervening processes linking CRP and fatigue in older individuals.
Major depressive disorder and subthreshold depression have been associated with premature mortality. We investigated the association between depressive symptoms and mortality across the full continuum of severity.
We used Cox proportional hazards models to examine the association between depressive symptom severity, assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D; range 0–8), and the risk of all-cause mortality over a 9-year follow-up, in 11 104 members of the English Longitudinal Study of Ageing.
During follow-up, one fifth of study members died (N = 2267). Depressive symptoms were associated with increased mortality across the full range of severity (ptrend < 0.001). Relative to study members with no symptoms, an increased risk of mortality was found in people with depressive symptoms of a low [hazard ratio (HR) for a score of 2 was 1.59, 95% confidence interval (CI) 1.40–1.82], moderate (score of 4: HR 1.80, 95% CI 1.52–2.13) and high (score of 8: HR 2.27, 95% CI 1.69–3.04) severity, suggesting risk emerges at low levels but plateaus thereafter. A third of participants (36.4%, 95% CI 35.5–37.3) reported depressive symptoms associated with an increased mortality risk. Adjustment for physical activity, physical illnesses, and impairments in physical and cognitive functioning attenuated this association (ptrend = 0.25).
Depressive symptoms are associated with an increased mortality risk even at low levels of symptom severity. This association is explained by physical activity, physical illnesses, and impairments in physical and cognitive functioning.
The present study aimed to assess nutritional status, dietary diversity and lifestyle risk factors associated with undernutrition in an institutionalised Sri Lankan elderly population.
The study was of cross-sectional design followed by a stratified sampling method.
Twelve homes for the elderly recruited from six provinces in Sri Lanka.
A total of 311 institutionalised elderly aged ≥60 years.
The mean age of the study population was 75 (sd 8) years. Prevalence of undernutrition was 30 %. Mean food variety score, dietary diversity score and dietary serving score of the study population were 8·7 (sd 1·5), 7·3 (sd 1·2) and 10·9 (sd 2·0), respectively. Mean daily intakes of fruit, vegetables, meat, fish, eggs and pulses and dairy portions were below the national recommendations, whereas the mean consumption of sugar exceeded the national recommendation. Only the mean intake of starch was within the recommendation. Food allergies (OR=8·0; 95 % CI 3·9, 16·2), skipping meals (OR=3·8; 95 % CI 2·0, 7·5) and lack of leisure activities (OR=3·1; 95 % CI 1·5, 6·7) significantly increased the risk of undernutrition, whereas the use of dentures decreased the risk (OR=0·20; 95 % CI 0·06, 0·69).
High prevalence of undernutrition and low dietary diversity were observed in an institutionalised elderly Sri Lankan population. Therefore, there is an urgent need to implement nutrition interventions as part of geriatric care to reduce undernutrition and improve the diets of the institutionalised elderly population in Sri Lanka.
The opisthobranch gastropod Hydatina physis (Linnaeus, 1758) is recorded from the north-west coast of India, off Veraval, Gujarat. A literature review on the distribution of this species revealed that this is the first report of H. physis from Indian waters since 1877 when a specimen collected from Chennai along the east coast of India and deposited in the Australian Museum was later identified to be H. physis. A note on the morphological features of this specimen is detailed in the present paper.
Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors’ knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia.
Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry.
The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals.
Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals.
Animal studies suggest that maternal separation is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis through effects that occur in a critical period following birth. Evidence for an association of the diurnal cortisol rhythm with maternal separation in humans is equivocal.
We examined whether maternal separation in childhood is associated with diurnal cortisol pattern in 3712 middle-aged men and women. Two aspects of cortisol release were examined: the cortisol awakening response (CAR) and the diurnal slope in cortisol throughout the day.
Maternal separation in childhood was reported by 12% of participants. Those participants who reported maternal separation had a larger CAR and flatter slopes in cortisol levels compared to those who did not report maternal separation [adjusted mean CAR in those reporting no separation versus separation: 7.1, 95% confidence interval (CI) 6.7–7.5 v. 8.4, 95% CI 7.3–9.5, p = 0.02, corresponding to adjusted mean diurnal slope: −0.129 (95% CI −0.130 to −0.128) v. −0.126 (95% CI −0.128 to −0.124), p = 0.01]. In participants who reported maternal separation, the age of separation was not associated with either cortisol measure (p = 0.11). The association between maternal separation and slope in cortisol secretion was largely explained by smoking behaviour and marital status at the time of sample collection whereas that of the CAR was explained by childhood psychosocial, material factors and adult health behaviours.
Our findings suggest that maternal separation in childhood is associated with alterations in the diurnal cortisol pattern in middle age. These associations are predominantly accounted for by adult circumstances and behaviours.
Converging evidence from pharmacological investigations, genetic association studies and schizophrenia research indicates an important influence of the dopamine system on sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response. In particular, D2 receptor agonists have been shown to disrupt PPI in humans and rodents. In the present study, we investigated the associations of two functional DRD2 related single nucleotide polymorphisms (rs4648317 and rs1800497, the latter also known as DRD2/ANKK1 Taq1A) with PPI in two independent healthy human samples (overall n=197; Munich n=101; London n=96). Taq1A is a prominent marker of striatal D2 receptor signalling and was therefore hypothesized to impact on PPI. In line with our hypothesis, we report here reduced PPI levels in individuals with higher striatal D2 receptor signalling as indicated by the Taq1A genotype. Meta-analysis across both samples confirmed this finding. In contrast, an association between rs4648317 and PPI found in the Munich sample could not be confirmed in the London sample. Overall, the present study helps to bridge the gap between pharmacological manipulations of PPI and molecular genetics of the dopaminergic system.