Distinct neural signatures of schizotypy and psychopathy during visual word-nonword recognition.

Previous behavioural data indicate lower word-nonword recognition accuracy in association with a high level of positive schizotypy, psychopathy, or motor impulsivity traits, each with some unique contribution, in the general population. This study aimed to examine the neural underpinnings of these associations using functional magnetic resonance imaging (fMRI) in a volunteer sample. Twenty-two healthy English-speaking adults completed self-report measures of schizotypy (Oxford-Liverpool Inventory of Feelings and Experiences [O-LIFE]), psychopathy (Triarchic Psychopathy Measure [TriPM]), and impulsivity (Barratt Impulsiveness Scale [BIS-11]) and underwent whole-brain fMRI while performing a lexical decision task (LDT) featuring high and low-frequency words, real nonwords, and pseudohomophones. Higher positive schizotypy (Unusual Experiences) was associated with lower cerebellum activity during identification of low-frequency words (over real nonwords). Higher Boldness (fearless dominance) and Meanness (callous aggression) facets of psychopathy were associated with lower striatal and posterior cingulate activity when identifying nonwords over words. Higher Motor Impulsivity was associated with lower activity in the fusiform (bilaterally), inferior frontal (right-sided), and temporal gyri (bilaterally) across all stimuli-types over resting baseline. Positive schizotypy, psychopathy, and impulsivity traits influence word-nonword recognition through distinct neurocognitive mechanisms. Positive schizotypy and psychopathy appear to influence LDT performance through brain areas that play only a supportive (cerebellum) or indirect role in reading-related skills. The negative association between Motor Impulsivity and activations typically found for phonological processing and automatic word identification indicates a reduced bilateral integration of the meaning and sound of mental word representations, and inability to select the appropriate outputs, in impulsive individuals.

Diurnal Preference and Grey Matter Volume in a Large Population of Older Adults: Data from the UK Biobank.

Eveningness (a diurnal preference for evening time) is associated with a number of negative health outcomes and risk and prevalence for psychiatric disorder. Our understanding of the anatomical substrates of diurnal preference, however, is limited. The current study used Voxel-Based Morphometry to compare grey matter volume in a large sample (N = 3730) of healthy adults determined by questionnaire to be either definite morning-type or definite evening-type. Eveningness was associated with increased grey matter volume in precuneus, brain regions implicated in risk and reward processing (bilateral nucleus accumbens, caudate, putamen and thalamus) and orbitofrontal cortex. These results indicate an anatomical-basis for diurnal preference which may underlie reported differences in behaviour and brain function observed in these individuals.

Late chronotype is associated with enhanced amygdala reactivity and reduced fronto-limbic functional connectivity to fearful versus happy facial expressions.

Increasing evidence suggests late chronotype individuals are at increased risk of developing depression. However, the underlying neural mechanisms that confer risk are not fully understood. Here, fifty healthy, right-handed individuals without a current or previous diagnosis of depression, family history of depression or sleep disorder underwent functional magnetic resonance imaging (FMRI). Participants completed an implicit emotion processing task (gender discrimination) including happy and fearful facial expressions. Linear effects of chronotype on BOLD response in bilateral amygdala were tested for significance using nonparametric permutation tests. Functional connectivity between amygdala and prefrontal cortex was also investigated using psychophysiological interaction (PPI) analysis. A significant negative correlation between BOLD response and chronotype was observed in bilateral amygdala where later chronotype was associated with an enhanced amygdala response to fearful vs. happy faces. This response remained significant after sleep quality, age, gender, mood, and time of scan were included as covariates in the regression model. Later chronotype was also significantly associated with reduced functional connectivity between amygdala and dorsal anterior cingulate cortex (dACC). The current results appear consistent with theories of impaired emotion regulation of the limbic system (particularly the amygdala) associated with depression and may, in part, explain the increased vulnerability for depression in late chronotype individuals.

Predicting Treatment Response in Depression: The Role of Anterior Cingulate Cortex.

Background: Identification of biomarkers predicting therapeutic outcome of antidepressant treatment is one of the most important tasks in current research because it may transform the lengthy process of finding the right treatment for a given individual with depression. In the current study, we explored the potential of pretreatment pregenual anterior cingulate cortex activity as a putative biomarker of treatment response. Methods: Thirty-two medication-free patients with depression were treated for 6 weeks with a selective serotonin reuptake inhibitor, escitalopram. Before treatment began, patients underwent an fMRI scan testing response to brief, masked, presentations of facial expression depicting sadness and happiness. Results: After 6 weeks of treatment, there were 20 selective serotonin reuptake inhibitor responders and 12 nonresponders. Increased pretreatment pregenual anterior cingulate cortex activity to sad vs happy faces was observed in responders relative to nonresponders. A leave-one-out analysis suggested that activity in the anterior cingulate cortex was able to predict response status at the level of the individual participant. Conclusions: The study supports the notion of pregenual anterior cingulate cortex as a promising predictor of antidepressant response.

A Bibliometric Analysis of the Top 100 Most Cited Chronotype Research Papers.

Bibliometric indices are a widely used measure of research impact. The aim of the current study was to identify and characterise the top one hundred most-cited research articles in the topic of chronotype research. A search of the Thomson Reuters Web of Science database returned 974 eligible articles (published between 1990 and 2016). Citations for the 100 most-cited articles ranged between 438 and 29. The most represented journal was Chronobiology International (n = 30). Nearly 50% of articles originated in Germany and the U.S. The bibliometrics reported identify key publications and provide insight into trends within the topic of chronotype research.

Muscle magnetic resonance imaging in congenital myasthenic syndromes.

INTRODUCTION: In this study we investigated muscle magnetic resonance imaging in congenital myasthenic syndromes (CMS). METHODS: Twenty-six patients with 9 CMS subtypes and 10 controls were imaged. T1-weighted (T1w) and short-tau inversion recovery (STIR) 3-Tesla MRI images obtained at thigh and calf levels were scored for severity. RESULTS: Overall mean the T1w score was increased in GFPT1 and DPAGT1 CMS. T1w scans of the AChR-deficiency, COLQ, and CHAT subjects were indistinguishable from controls. STIR images from CMS patients did not differ significantly from those of controls. Mean T1w score correlated with age in the CMS cohort. CONCLUSIONS: MRI appearances ranged from normal to marked abnormality. T1w images seem to be especially abnormal in some CMS caused by mutations of proteins involved in the glycosylation pathway. A non-selective pattern of fat infiltration or a normal-appearing scan in the setting of significant clinical weakness should suggest CMS as a potential diagnosis. Muscle MRI could play a role in differentiating CMS subtypes. Muscle Nerve 54: 211-219, 2016.

Sleep quality mediates the association between chronotype and mental health in young Indian adults.

There is increasing recognition of 'higher preference for eveningness' as a potential independent risk factor for poor mental health. To examine the chronotype-mental health relationship while also quantifying the potential roles of poor sleep quality, relevant personality traits, and childhood trauma, we assessed 282 young adults (18-40 years; 195 females) residing in North India, between January and March 2023 (to control for seasonal variation), using self-report measures of diurnal preference, sleep patterns, mental health (depression, anxiety, and stress), personality traits (extraversion, neuroticism, schizotypy, and impulsivity), and childhood trauma. The results showed a significant association between eveningness and poor mental health but this association was fully mediated by poor sleep quality. Neuroticism, emotional abuse and cognitive disorganisation were correlated with eveningness as well as with poor mental health and sleep quality. Neuroticism and emotional abuse, but not cognitive disorganisation, also had indirect effects on mental health via sleep quality. Our findings highlight the crucial role played by sleep quality in the chronotype-mental health relationship.

Beyond sleep: A multidimensional model of chronotype.

Chronotype can be defined as an expression or proxy for circadian rhythms of varied mechanisms, for example in body temperature, cortisol secretion, cognitive functions, eating and sleeping patterns. It is influenced by a range of internal (e.g., genetics) and external factors (e.g., light exposure), and has implications for health and well-being. Here, we present a critical review and synthesis of existing models of chronotype. Our observations reveal that most existing models and, as a consequence, associated measures of chronotype have focused solely or primarily on the sleep dimension, and typically have not incorporated social and environmental influences on chronotype. We propose a multidimensional model of chronotype, integrating individual (biological and psychological), environmental and social factors that appear to interact to determine an individual's true chronotype with potential feedback loops between these factors. This model could be beneficial not only from a basic science perspective but also in the context of understanding health and clinical implications of certain chronotypes as well as designing preventive and therapeutic approaches for related illnesses.

Positive schizotypy and Motor Impulsivity correlate with response aberrations in ventral attention network during inhibitory control.

Inhibitory control (IC) aberrations are present in various psychopathologies, including schizophrenia spectrum and personality disorders, especially in association with antisocial or violent behaviour. We investigated behavioural and neural associations between IC and psychopathology-related traits of schizotypy [Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)], psychopathy [Triarchic Psychopathy Measure (TriPM)], and impulsivity [Barratt Impulsiveness Scale (BIS-11)], using a novel Go/No-Go Task (GNG) featuring human avatars in 78 healthy adults (25 males, 53 females; mean age = 25.96 years, SD = 9.85) and whole-brain functional magnetic resonance imaging (fMRI) in a separate sample of 22 right-handed healthy individuals (7 males, 15 females; mean age = 24.13 years, SD = 5.40). Behaviourally, O-LIFE Impulsive Nonconformity (impulsive, anti-social, and eccentric behaviour) significantly predicted 16 % of variance in false alarms (FAs). O-LIFE Unusual Experiences (positive schizotypy) and BIS-11 Motor Impulsivity predicted 15 % of d prime (d') (sensitivity index) for the fastest (400 ms) GNG trials. When examined using fMRI, higher BIS-11 Motor Impulsivity uniquely, and also together with Unusual Experiences, was associated with lower activity in the left lingual gyrus during successful inhibition (correct No-Go over baseline). Additionally, higher Impulsive Nonconformity was associated with lower activity in the caudate nucleus and anterior cingulate during No-Go compared to Go stimuli reactions. Positive schizotypy, motor, and antisocial-schizotypal impulsivity correlate with some common but mostly distinct neural activation patterns during response inhibition in areas within or associated with the ventral attention network.

Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate.

Increasing interest surrounds potential neuroprotective or neurotrophic actions of antidepressants. While growing evidence points to important early clinical and neuropsychological effects of antidepressants, the time-course of any effect on neuronal integrity is unclear. This study used magnetic resonance spectroscopy to assess effects of short-term treatment with escitalopram on N-acetyl-aspartate (NAA), a marker of neuronal integrity. Thirty-nine participants with major depression were randomly assigned to receive either 10 mg escitalopram or placebo daily in a double-blind, parallel group design. On the seventh day of treatment, PRESS data were obtained from a 30×30×20 mm voxel placed in medial frontal cortex. Age and gender-matched healthy controls who received no treatment were also scanned. Levels of NAA were significantly higher in patients treated with escitalopram than in either placebo-treated patients (p<0.01) or healthy controls (p<0.01). Our findings are consistent with the proposition that antidepressant treatment in depressed patients can produce early changes in neuronal integrity.

Elevated cortical glutamate in young people at increased familial risk of depression.

Using proton magnetic resonance spectroscopy (MRS), we have demonstrated regional abnormalities in cortical γ-aminobutyric acid (GABA) and glutamate in medication-free recovered depressed patients. It is unclear whether these changes represent an underlying trait vulnerability to depression, or an after-effect of episodes of illness or its treatment. We sought to examine this question by examining a group of high-risk, never-depressed, individuals. We used MRS to measure GABA and glutamate in parieto-occipital cortex in young people (ages 16-21 yr) with a family history of parental depression (n=24) but no personal history of illness and a control group without a history of depression in any first-degree relative (n=28). Participants with a parental history of depression had significantly higher levels of glutamate than controls in parieto-occipital cortex (F1,47=5.5, p=0.02). These findings suggest that abnormalities in glutamate neurotransmission may reflect a trait marker of vulnerability to depression.

Diurnal preference and depressive symptomatology: a meta-analysis.

Eveningness, a preference for later sleep and rise times, has been associated with a number of negative outcomes in terms of both physical and mental health. A large body of evidence links eveningness to Major Depressive Disorder (MDD). However, to date, evidence quantifying this association is limited. The current meta-analysis included 43 effect sizes from a total 27,996 participants. Using a random-effects model it was demonstrated that eveningness is associated with a small effect size (Fisher's Z = - 2.4, 95% CI [- 0.27. - 0.21], p < 0.001). Substantial heterogeneity between studies was observed, with meta-regression analyses demonstrating a significant effect of mean age on the association between diurnal preference and depression. There was also evidence of potential publication bias as assessed by visual inspection of funnel plots and Egger's test. The association between diurnal preference and depression is small in magnitude and heterogenous. A better understanding of the mechanistic underpinnings linking diurnal preference to depression and suitably powered prospective studies that allow causal inference are required.

Loneliness in the time of COVID.

In the effort to limit the transmission of COVID-19, countries around the world have instigated extended periods of restricted movement that has significantly impacted work, leisure, and social interaction. An indirect outcome of these restrictions is increased loneliness and social isolation. Here, data from an online survey carried out in the latter part 2020/early 2021, demonstrated that evening-type is associated with increased odds of reporting self-perceived loneliness, but with no evidence for a similar association in neither-types. What future working and leisure patterns (the 'new normal') will look like is unclear. Nevertheless, the current data suggest eveningness should be a consideration in any interventions designed to reduce the impact of loneliness on physical and mental health.

Associations between diurnal preference, impulsivity and substance use in a young-adult student sample.

A diurnal preference for eveningness is common in young adulthood and previous research has associated eveningness with anxiety symptoms as well as increased smoking and alcohol use behaviors. There is some evidence that impulsivity might be an important explanatory variable in these associations, but this has not been comprehensively researched. Here we used both subjective and objective measures of impulsivity to characterize impulsive tendencies in young adults and investigated whether trait impulsivity or trait anxiety could mediate the link between eveningness and substance use. A total of 191 university students (169 females), age range 18-25 y, completed the study. Diurnal preference, sleep quality, anxiety, impulsivity, and substance use were assessed by questionnaire. Impulsivity was also measured using a delay discounting task. Eveningness correlated with trait anxiety and trait impulsivity, and these associations were still significant after controlling for sleep quality. On the delayed discounting task, eveningness correlated with a tendency to prefer smaller immediate rewards over delayed, larger ones. Evening types also reported higher levels of alcohol and cigarette use even after controlling for sleep quality. These associations were found to be completely mediated by self-reported impulsivity; anxiety did not contribute. The current results could help inform interventions aiming to reduce substance use in young adult populations.

Associations between number of siblings, birth order, eating rate and adiposity in children and adults.

Eating quickly is associated with eating larger amounts at mealtimes and faster eaters tend to have a higher BMI. Evidence suggests that sibling structure influences the development of childhood eating behaviours. We hypothesized that number of siblings and birth order might play a role in the development of eating rate. In two UK studies, children in Bristol (n = 132; Study 1) and adults and children in London (adults n = 552, children n = 256; Study 2) reported their eating rate, number of siblings, and birth order. A BMI measurement was obtained and in Study 2 waist circumference was recorded. Ordered logistic regression was used to examine effects of sibling structure on eating rate and linear regression assessed effects of eating rate on BMI. Faster eating was associated with higher BMI and a larger waist, in children and adults (ps < .01). In Study 1, first-born children were twice as likely to eat faster compared to children who were not first-born (P < .04). In Study 2, only-child adults reported eating slower than adults who were not first-born (P < .003). Additionally, higher number of siblings was associated with faster eating rate in children from Bristol (P < .05), but not in children from London. London adults without siblings ate slower than those with two or more (P = .01), but having one sibling was associated with eating faster than having two or more (P = .01). These findings reveal how birth order and number of siblings might influence eating rate. Exploring these relationships through direct observation would be beneficial in future studies.

Risk for depression and neural responses to fearful facial expressions of emotion.

BACKGROUND: Depression is associated with neural abnormalities in emotional processing. AIMS: This study explored whether these abnormalities underlie risk for depression. METHOD: We compared the neural responses of volunteers who were at high and low-risk for the development of depression (by virtue of high and low neuroticism scores; high-N group and low-N group respectively) during the presentation of fearful and happy faces using functional magnetic resonance imaging (fMRI). RESULTS: The high-N group demonstrated linear increases in response in the right fusiform gyrus and left middle temporal gyrus to expressions of increasing fear, whereas the low-N group demonstrated the opposite effect. The high-N group also displayed greater responses in the right amygdala, cerebellum, left middle frontal and bilateral parietal gyri to medium levels of fearful v. happy expressions. CONCLUSIONS: Risk for depression is associated with enhanced neural responses to fearful facial expressions similar to those observed in acute depression.

Chronotype, depression and hippocampal volume: cross-sectional associations from the UK Biobank.

Diurnal preference for evening time has been associated with increased odds for current depression and a number of indices of the disorder. In the current study, the association between chronotype and depression was explored in a population-based sample of 5360 adults aged between 40 and 70 years. Previous work has also suggested that larger hippocampal volume may be protective against depression. In an additional, exploratory analysis, hippocampal volume was compared in never-depressed early and late chronotypes (N= 3004). Definite eveningness was significantly associated with increased odds for probable lifetime depression after controlling for a number of confounding factors including neuroticism. Hippocampal volume did not differ between never-depressed early and late chronotypes. The current results extend previous work and add further weight to the argument that late chronotype represents a risk factor for depression.

Time to think: Subjective sleep quality, trait anxiety and university start time.

Poor quality sleep is related to mental health and there is increasing interest in student wellbeing and mental health. The aim of the current study was to evaluate sleep quality, daytime dozing, anxiety proneness, chronotype and preferred start time in a sample of university students. A total of 546 university students (age range, 18-55) from two university located in South East England were included and completed an online survey. Participants' self-reported age, gender, year and field of study. Sleep quality, anxiety, daytime dozing, coffee/caffeine/tobacco use (coded as binary variables), preferred start time and chronotype were also recorded. Data were analysed using independent samples t-tests, chi-square, simple mediation-analyses and Analysis of Variance. Across the entire sample 46% percent of participants rated their sleep as fairly bad or very bad. Poor quality sleep was associated with significantly higher levels of anxiety which was not mediated by chronotype. Poor quality sleep is more prevalent in the first year of university and our sample endorsed a start time for university activities approximately 2 h later than currently timetabled. The current findings demonstrate that a large proportion of students are chronically sleep deprived, obtaining, on average, less than 7 h sleep per night on week days and this was more marked in first year students. In addition, we show that poor sleep is associated with increased anxiety. Based on the current evidence the authors suggest a review of current university timetabling and examination scheduling merits immediate consideration by policy makers and educators.

Risk for depression is associated with neural biases in emotional categorisation.

Negative biases in emotional processing are a major characteristic of depression. Recent research has shown that such negative biases are evident in high risk individuals even in the absence of personal history of depression, suggesting that they may serve as key vulnerability markers of depression. However, the neural basis of these behavioural observations has not been fully explored. This study therefore aimed to (1) illustrate the neural processes involved in the categorisation of emotional personality-trait words; and (2) examine whether these neural mechanisms are biased towards negative information in high risk individuals. Risk for depression was defined by high neuroticism (N). We recruited a sample of high risk (high N) and low risk (low N) never-depressed young adults. Functional magnetic resonance imaging (fMRI) was acquired during the categorisation and memory for positive and negative self-referent personality-trait words (e.g. honest, rude). High risk volunteers showed greater responses in the right superior parietal cortex than low risk volunteers specifically during the categorisation of negative words. Moreover, neuroticism score was positively correlated with neural responses in the left anterior cingulate during the categorisation of negative words but negatively correlated within the same region during the retrieval of these words. These results highlight a role of the fronto-parietal circuitry in emotional processing and further suggest that negative biases in these neural processes may be involved in risk for depression.

Altered resting-state connectivity within default mode network associated with late chronotype.

Current evidence suggests late chronotype individuals have an increased risk of developing depression. However, the underlying neural mechanisms of this association are not fully understood. Forty-six healthy, right-handed individuals free of current or previous diagnosis of depression, family history of depression or sleep disorder underwent resting-state functional Magnetic Resonance Imaging (rsFMRI). Using an Independent Component Analysis (ICA) approach, the Default Mode Network (DMN) was identified based on a well validated template. Linear effects of chronotype on DMN connectivity were tested for significance using non-parametric permutation tests (applying 5000 permutations). Sleep quality, age, gender, measures of mood and anxiety, time of scan and cortical grey matter volume were included as covariates in the regression model. A significant positive correlation between chronotype and functional connectivity within nodes of the DMN was observed, including; bilateral PCC and precuneus, such that later chronotype (participants with lower rMEQ scores) was associated with decreased connectivity within these regions. The current results appear consistent with altered DMN connectivity in depressed patients and weighted evidence towards reduced DMN connectivity in other at-risk populations which may, in part, explain the increased vulnerability for depression in late chronotype individuals. The effect may be driven by self-critical thoughts associated with late chronotype although future studies are needed to directly investigate this.