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The prefrontal deficits in psychiatric disorders have been investigated using functional neuroimaging tools; however, no studies have tested the related characteristics across psychiatric disorders considering various demographic and clinical confounders.
We analyzed 1558 functional brain measurements using a functional near-infrared spectroscopy during a verbal fluency task from 1200 participants with three disease spectra [196 schizophrenia, 189 bipolar disorder (BPD), and 394 major depressive disorder (MDD)] and 369 healthy controls along with demographic characteristics (age, gender, premorbid IQ, and handedness), task performance during the measurements, clinical assessments, and medication equivalent doses (chlorpromazine, diazepam, biperiden, and imipramine) in a consistent manner. The association between brain functions and demographic and clinical variables was tested using a general linear mixed model (GLMM). Then, the direction of relationship between brain activity and symptom severity, controlling for any other associations, was estimated using a model comparison of structural equation models (SEMs).
The GLMM showed a shared functional deficit of brain activity and a schizophrenia-specific delayed activity timing in the prefrontal cortex (false discovery rate-corrected p < 0.05). Comparison of SEMs showed that brain activity was associated with the global assessment of functioning scores in the left inferior frontal gyrus opercularis (IFGOp) in BPD group and the bilateral superior temporal gyrus and middle temporal gyrus, and the left superior frontal gyrus, inferior frontal gyrus triangularis, and IFGOp in MDD group.
This cross-disease large-sample neuroimaging study with high-quality clinical data reveals a robust relationship between prefrontal function and behavioral outcomes across three major psychiatric disorders.
The aim of this study was to identify possible peripheral biological markers (both lipidic and hormonal) which can be easily used for the early detection of parasuicidal behaviour and to propose a predictive biological model of such behaviour. A case-control analytical study was undertaken at least 3 months after attempted suicide. Study was made of 128 patients who presented at the University General Hospital of Oviedo (Spain) with signs of self-intoxication. Lipidic and hormonal profiles were measured under basal conditions and comparison was made with a control group of healthy volunteer donors obtained from the Oviedo General Hospital blood bank. A discriminant analysis was later made with the aim of establishing a predictive biological model. This included the following variables: cholesterol, HDL-C, LDL-C and cortisol. Sensitivity and specificity were 62.5% and 65.6%, respectively. Replication and improvement of this model, through other prospective studies, could lead to the use of serum cholesterol and cortisol levels as inexpensive and readily available markers of suicide risk.
Despite over a century of intensive research, no single biological marker has successfully translated into daily clinical practice. A key challenge in psychiatric research is that traditional diagnostic categories represent phenomenological constructs that do not necessarily circumscribe a biological homogenous entity, but encompass a whole range of disorders presenting with similar phenotypes. The clinical staging model shifts our focus to search for markers relevant to particular stages of mental disorders and provides a useful framework to differentiate overlapping and heterogeneous syndromes. The identification of such “stage” dependant markers may be more meaningful and of greater prognostic and therapeutic value than our quest for categorical disease markers. In this chapter, bioactive and inflammatory markers in emerging psychotic disorders are discussed. Their specific role in brain development, psychiatric disorder onset and management are reviewed. Implications for future research are also provided.
For over a decade a transdiagnostic clinical staging framework for youth with anxiety, mood and psychotic disorders (linked with measurement of multidimensional outcomes), has been utilised in over 8,000 young people presenting to the enhanced primary (headspace) and secondary care clinics of the Brain and Mind Centre of the University of Sydney. This framework has been evaluated alongside a broad range of other clinical, neurobiological, neuropsychological, brain imaging, circadian, metabolic, longitudinal cohort and controlled intervention studies. This has led to specific tests of its concurrent, discriminant and predictive validity. These extensive data provide strong preliminary evidence that: i) varying stages of illness are associated with predicted differences in a range of independent and objectively measured neuropsychological and other biomarkers (both cross-sectionally and longitudinally); and, ii) that earlier stages of illness progress at variable rates to later and more severe or persistent disorders. Importantly, approximately 15-20% of those young people classed as stage 1b or ‘attenuated’ syndromes at presentation progress to more severe or persistent disorders. Consequently, this cohort should be the focus of active secondary prevention trials. In clinical practice, we are moving to combine the staging framework with likely pathophysiological paths (e.g. neurodevelopmental-psychotic, anxiety-depression, circadian-bipolar) to underpin enhanced treatment selection.
Since its development and theorisation in the 60s, attachment theory has greatly influenced both clinical and developmental psychology suggesting the existence of complex dynamics based on the relationship between an infant and its caregiver, that affects personality traits and interpersonal relationships in adulthood. Many studies have been conducted to explore the association between attachment styles and psychosocial functioning and mental health. By contrast, only a few studies have investigated the neurobiological underpinnings of attachment style, showing mixed results. Therefore, in this review, we described current evidence from structural and functional imaging studies with the final aim to disentangle the neural correlates of attachment style in healthy individuals. Overall, different attachment styles have been correlated with volumetric alterations mainly in the cingulate cortex, amygdala, hippocampus and anterior temporal pole. Consistently, functional imaging studies suggested patterns of activations in fronto-striatal-limbic circuits during the processing of social and attachment-related stimuli. Further studies are needed to clarify the neurobiological signature of attachment style, possibly taking into consideration a wide range of demographic, psychosocial and clinical factors that may mediate the associations between the style of attachment and brain systems (e.g., gender, personality traits, psychosocial functioning, early-life experience).
Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms.
In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)].
Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS.
Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
This study assessed the relationship between vascular endothelial growth factor expression and the laryngeal cancer prognosis.
Systematic computerised searches of PubMed were performed up to 31 January 2015. Prognostic endpoints were overall survival and disease-free survival. The pooled hazard ratios for overall survival and disease-free survival were also calculated.
Seven studies containing 975 patients were included. The pooled hazard ratio was 1.703 (95 per cent confidence interval, 1.373 to 2.112; z score = 4.85, p = 0.000) for overall survival and was 1.918 (95 per cent confidence interval, 1.410 to 2.609; z score = 4.15, p = 0.000) for disease-free survival. No significant publication bias was found. A sensitivity analysis showed that the results were robust. Power analyses also showed there was enough power to detect the calculated hazard ratios.
The study found that vascular endothelial growth factor overexpression predicted a worse prognosis for laryngeal cancer patients. This supports a strategy of targeted therapy by blocking the vascular endothelial growth factor receptor.
The time required in completing the 26 items of neurological examinations in the standard Neurological Evaluation Scale (NES) may limit its utility in pragmatic clinical situations. We propose the Short Neurological Evaluation Scale (S-NES) for use in busy clinical settings, and in research.
Using confirmatory factor analyses, we identified 12 items of neurological examination showing significant overlap with previously reported theoretical and empirical categories of neurological soft signs (NSS) in schizophrenia. This provided justification for the development of a shorter version of the NES based on the empirically identified NSS. In the present study, we relied on existing data to present an initial validation of the S-NES against the referent standard 26-item NES. We determined sensitivity, specificity, and likelihood ratios. Posterior-test probability was estimated using a Bayesian nomogram plot.
Using data derived from 84 unmedicated or minimally treated patients with first-episode schizophrenia, 12 empirically determined items of neurological examinations showed high agreement with the 26 items in the standard NES battery (sensitivity=96.3%, specificity=100%, and posterior-test probability=100%).
Within limitations of validity estimates derived from existing data, the present results suggest that the design of the S-NES based on empirically identified 12 items of neurological examination is a logical step. If successful, the S-NES will be useful for rapid screening of NSS in busy clinical settings, and also in research.
Objectives: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. Methods: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. Results: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. Conclusions: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785–789)
Myxozoans have been successfully used as tags for fish stock identification around the world. However, few studies using myxozoan tags have been carried out in the Southern Atlantic, a region with complex oceanography that constitutes a potentially suitable scenario for testing the utility of myxozoans as indicators. Its usefulness was tested using six samples of Merluccius hubbsi in two different regions of the Argentine Sea. Generalized linear models were performed to assess the effects of fish size and sex, and year and region of capture and selected using the Information Theoretic approach. Three myxozoan species were recorded: Kudoa rosenbuschi, Myxoproteus meridionalis and Fabespora sp. Results of modelling species individually showed differential capabilities for detecting geographical population structure at different spatial scales, with K. rosenbuschi and Fabespora sp. allowing the discrimination of northern and southern stocks, but Fabespora sp. also as a promissory indicator of intrapopulation sub-structure due to different migratory routes during non-reproductive periods. This work confirms that myxozoans offer a set of suitable markers at different spatial scales, which can be selected individually or in any combination, depending on the geographical extent of the study, constituting tools adaptable to the objectives of further research on fish population structure.
Evidence from previous studies has reported that complex traits, including psychiatric disorders, are moderately to highly heritable. Moreover, it has also been shown that specific personality traits may increase the risk to develop mental illnesses. Therefore the focus of the research shifted towards the identification of the biological mechanisms underpinning these traits by exploring the effects of a constellation of genetic polymorphisms in healthy subjects. Indeed, studying the effect of genetic variants in normal personality provides a unique means for identifying candidate genes which may increase the risk for psychiatric disorders. In this review, we discuss the impact of two of the most frequently studied genetic polymorphisms on personality in healthy subjects, the 5-HTT polymorphism of the serotonin transporter and the DRD2/DRD4 polymorphisms of the D2/D4 dopamine's receptors. The main aims are: (a) to highlight that the study of candidate genes provides a fruitful ground for the identification of the biological underpinnings of personality without, though, reaching a general consensus about the strength of this relationship; and (b) to outline that the research in personality genetics should be expanded to provide a clearer picture of the heritability of personality traits.
Biomarkers are increasingly being used in many cancers to select patients for oncological treatment paradigms based on their inherent genetic properties. However, in head and neck cancers, there are no personalised therapies available outside the context of a clinical trial. A number of studies suggest there are intrinsic tumour properties of head and neck cancers that affect their response to chemotherapeutic agents. This paper aimed to review their evidence base.
A narrative review was conducted following a search of the PubMed database.
Results and conclusion:
The review identified a number of biomarkers predicting response to chemotherapy in head and neck cancers. The paper discusses these in detail, and explores where future research could be directed in order to deliver personalised therapies for patients with head and neck cancers.
Offspring of parents with bipolar disorder (BD) (BO) are at higher risk of BD than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC.
BO (n = 29; mean age = 13.8 years; 14 female), NBO (n = 28; mean age = 13.9 years; 12 female) and HC (n = 23; mean age = 13.7 years; 11 female) were scanned while performing a number-guessing reward task. Of the participants, 11 BO and 12 NBO had current non-BD psychopathology; five BO and four NBO were taking psychotropic medications.
A 3 (group) × 2 (conditions: win-control/loss-control) analysis of variance revealed a main effect of group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster-p < 0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses.
This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO v. healthy NBO v. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.
Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N=238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. (JINS, 2015, 21, 573–583)
Although we have gained enormous insights into neurobiological and psychological underpinnings of bipolar disorder (BD) symptoms, our knowledge concerning pathogenic mechanisms initiating recurrent affective episodes is still fragmentary. Previous research has highlighted the role of significant life events and social rhythm in recurrent episodes of mania and depression. However, most studies share the drawback of retrospective self-report data, which are prone to recall biases and limited introspective abilities. Therefore, more objective data, such as neuropsychological and neurobiological measures are needed to further unravel the pathogenic mechanisms of the dynamics of bipolar disorder. Previous research has highlighted disturbed emotional reactivity as well as impaired emotion regulation and impulse control as major behavioural characteristics of BD and aberrancies in prefrontal–limbic–striatal networks that have been proposed to be the correlates of these behavioural alterations. However, longitudinal studies assessing these neural and behavioural alterations are rare. Future research should therefore adopt prospective study designs including behavioural and neuroimaging measures underlying cognitive, emotional and motivational deficits in bipolar disorder. Particularly, these measures should be collected continuously at multiple time points as implemented in modern ambulatory assessment tools.
Nasal polyposis is one of the most common inflammatory pathologies of the nasal cavity. Eosinophilic inflammation plays an important role in the pathogenesis. This study aimed to investigate soluble tumour necrosis factor related apoptosis-inducing ligand levels and eosinophil count in nasal polyposis patients.
The study was performed on 24 adult nasal polyposis patients and 24 age-matched healthy individuals. The patients had not received any medical or surgical treatment. Pre-operative computed tomography scans were assessed using the Lund–MacKay grading system, and soluble tumour necrosis factor related apoptosis-inducing ligand levels were measured with a sandwich enzyme-linked immunosorbent assay.
Compared with controls, eosinophil levels in nasal polyposis patients were increased (p = 0.024), but there was no significant difference in soluble tumour necrosis factor related apoptosis-inducing ligand levels (p = 0.529). The Lund–Mackay mean grading was 12.43 ± 6.9. There was no correlation between soluble tumour necrosis factor related apoptosis-inducing ligand level and Lund–Mackay grading and eosinophil count.
There was no relationship between soluble tumour necrosis factor related apoptosis-inducing ligand level and blood eosinophil or clinical markers; however, soluble tumour necrosis factor related apoptosis-inducing ligand level remains of interest for future studies.
Although neurobiological mechanisms of bipolar disorder (BD) are still unclear, neural models of the disease have recently been conceptualised thanks to neuroimaging. Indeed, magnetic resonance imaging (MRI) studies investigating structural and functional connectivity between different areas of the brain suggest an altered prefrontal–limbic coupling leading to disrupted emotional processing in BD, including uncinate fasciculus, amygdala, parahippocampal cortex, cingulate cortex as well corpus callosum. Specifically, these models assume an altered prefrontal control over a hyperactivity of the subcortical limbic structures implicated in automatic emotional processing. This impaired mechanism may finally trigger emotional hyper-reactivity and mood episodes. In this review, we first summarised some key neuroimaging studies on BD. In the second part of the work, we focused on the heterogeneity of the available studies. This variability is partly due to methodological factors (i.e., small sample size) and differences among studies (i.e., MRI acquisition and post-processing analyses) and partly to the clinical heterogeneity of BD. We finally outlined how epidemiological studies should indicate which risk factors and clinical dimensions of BD are relevant to be studied with neuroimaging in order to reduce heterogeneity and go beyond diagnostic categories.
Many marine fisheries in South American Atlantic coasts (SAAC) are threatened by overfishing and under serious risk of collapsing. The SAAC comprises a diversity of environments, possesses a complex oceanography and harbours a vast biodiversity that provide an enormous potential for using parasites as biological tags for fish stock delineation, a prerequisite for the implementation of control and management plans. Here, their use in the SAAC is reviewed. Main evidence is derived from northern Argentine waters, where fish parasite assemblages are dominated by larval helminth species that share a low specificity, long persistence and trophic transmission, parasitizing almost indiscriminately all available fish species. The advantages and constraints of such a combination of characteristics are analysed and recommendations are given for future research. Shifting the focus from fish/parasite populations to communities allows expanding the concept of biological tags from local to regional scales, providing essential information to delineate ecosystem boundaries for host communities. This new concept arose as a powerful tool to help the implementation of ecosystem-based approaches to fisheries management, the new paradigm for fisheries science. Holistic approaches, including parasites as biological tags for stock delineation will render valuable information to help insure fisheries and marine ecosystems against further depletion and collapse.
The validity of using FFQ to assess dietary lignans is uncertain. We aimed to validate the use of FFQ for the assessment of dietary intake of lignans compared to the serum biomarker enterolactone, the main product of dietary lignans' metabolism in human subjects. A random sample of women, aged 55–75 years, from the Swedish Mammography Cohort was selected. Information from two FFQ, the FFQ-87 (sixty-seven food items) and the FFQ-97 (ninety-three food items), and blood samples were collected. Dietary intake of lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol and syringaresinol) was assessed by the FFQ. Serum concentrations of enterolactone were analysed by time-resolved fluoroimmunoassay. The correlation coefficient between energy-adjusted lignan intake and serum enterolactone was estimated in crude and multivariable-adjusted models, taking into account the factors potentially influencing the serum enterolactone. Among the 135 participants aged 55–75 years, with a mean BMI of 26·7 kg/m2, the average energy-adjusted intake of total lignans was 1616 (sd 424) and 1516 (sd 409) μg/d according to the FFQ-87 (forty-five food items containing lignans) and the FFQ-97 (sixty-five food items containing lignans), respectively. The mean concentration of serum enterolactone was 23·2 (sd 15·4) nmol/l. The adjusted Pearson's correlation between dietary intake of lignans assessed by the FFQ-97 and serum enterolactone was statistically significant (r 0·22, P= 0·01). No significant correlation was observed for the FFQ-87 (r 0·09, P= 0·30). The present study indicates that the FFQ-97 might be better than the FFQ-87 for assessing dietary intake of lignans, although the correlation was low.
To assess the strength of the relationships between serum carotenoids and three self-reported dietary intake instruments often used to characterize carotenoid intake in studies of diet and disease.
Participants completed a Diet History Questionnaire (DHQ), two 24 h dietary recalls (24HR), a fruit and vegetable screener and a fasting blood draw. We derived dietary intake estimates of α-carotene, β-carotene, cryptoxanthin, lutein, zeaxanthin and lycopene from each diet instrument and calculated sex-specific multivariate correlations between dietary intake estimates and their corresponding serum values.
Montgomery County, Maryland, USA.
Four hundred and seventy women and men aged 40–69 years in the National Cancer Institute's Observing Protein and Energy Nutrition (OPEN) Study.
Serum carotenoids correlated more strongly with the DHQ (r = 0·34–0·54 for women; r = 0·38–0·56 for men) than with the average of two recalls (r = 0·26–0·47 for women; r = 0·26–0·40 for men) with the exception of zeaxanthin, for which the correlations using recalls were higher. With adjustment for within-person variation, correlations between serum carotenoids and recalls were greatly improved (r = 0·38–0·83 for women; r = 0·42–0·74 for men). In most cases, correlations between serum carotenoids and the fruit and vegetable screener resembled serum–DHQ correlations.
Evidence from the study provides support for the use of the DHQ, a fruit and vegetable screener and deattenuated recalls for estimating carotenoid status in studies without serum measures, and draws attention to the importance of adjusting for intra-individual variability when using recalls to estimate carotenoid values.