To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Stress can exert modulatory effects on pain perception in animals, as exposure to a stressor can result in either the reduction or amplification of the perceived severity of pain. These phenomena are widely described as stress-induced analgesia (SIA) and stress-induced hyperalgesia (SIH). The two are mediated by the same underlying mechanisms, but occur due to different stressors and different responses from the pain pathway. SIA and SIH have been demonstrated with a variety of stress and pain stimuli in rodents, humans and other mammals. There is some evidence that SIA occurs in birds and that they have the neurological systems and brain regions necessary for SIH. Tonic immobility (TI) is related to SIA in mammals, and there is evidence the avian brain is compatible with TI having analgesic effect, but it could have a hyperalgesic effect. This review looks at the mechanisms and evidence of SIA, SIH and TI in mammals and discusses evidence relating to the occurrence of these phenomena in birds.
Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.
While child poverty is a significant risk factor for poor mental health, the developmental pathways involved with these associations are poorly understood. To advance knowledge about these important linkages, the present study examined the developmental sequelae of childhood exposure to poverty in a multiyear longitudinal study. Here, we focused on exposure to poverty, neurobiological circuitry connected to emotion dysregulation, later exposure to stressful life events, and symptoms of psychopathology. We grounded our work in a biopsychosocial perspective, with a specific interest in “stress sensitization” and emotion dysregulation. Motivated by past work, we first tested whether exposure to poverty was related to changes in the resting-state coupling between two brain structures centrally involved with emotion processing and regulation (the amygdala and the ventromedial prefrontal cortex; vmPFC). As predicted, we found lower household income at age 10 was related to lower resting-state coupling between these areas at age 15. We then tested if variations in amygdala–vmPFC connectivity interacted with more contemporaneous stressors to predict challenges with mental health at age 16. In line with past reports showing risk for poor mental health is greatest in those exposed to early and then later, more contemporaneous stress, we predicted and found that lower vmPFC–amygdala coupling in the context of greater contemporaneous stress was related to higher levels of internalizing and externalizing symptoms. We believe these important interactions between neurobiology and life history are an additional vantage point for understanding risk and resiliency, and suggest avenues for prediction of psychopathology related to early life challenge.
Psychopathy is a personality type characterized by both callous emotional dysfunction and deviant behavior that affects society in the form of actions that harm others. Historically, researchers have been concerned with seeking data and arguments to support a neurobiological foundation of psychopathy. In the past few years, increasing research has begun to reveal brain alterations putatively underlying the enigmatic psychopathic personality. In this review, we describe the brain anatomical and functional features that characterize psychopathy from a synthesis of available neuroimaging research and discuss how such brain anomalies may account for psychopathic behavior. The results are consistent in showing anatomical alterations involving primarily a ventral system connecting the anterior temporal lobe to anterior and ventral frontal areas, and a dorsal system connecting the medial frontal lobe to the posterior cingulate cortex/precuneus complex and, in turn, to medial structures of the temporal lobe. Functional imaging data indicate that relevant emotional flow breakdown may occur in both these brain systems and suggest specific mechanisms via which emotion is anomalously integrated into cognition in psychopathic individuals during moral challenge. Directions for future research are delineated emphasizing, for instance, the relevance of further establishing the contribution of early life stress to a learned blockage of emotional self-exposure, and the potential role of androgenic hormones in the development of cortical anomalies.
Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.
The current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).
EPA and DHA appear to be the most important n-3 fatty acids, but roles for n-3 docosapentaenoic acid are now also emerging. Intakes of EPA and DHA are usually low, typically below those recommended. Increased intakes result in higher concentrations of EPA and DHA in blood lipids, cells and tissues. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins. EPA and DHA modulate the production of lipid mediators and through effects on cell signalling can alter the patterns of gene expression. Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a way that often results in more optimal conditions for growth, development and maintenance of health. DHA has vital roles in brain and eye development and function. EPA and DHA have a wide range of physiological roles, which are linked to certain health or clinical benefits, particularly related to CVD, cancer, inflammation and neurocognitive function. The benefits of EPA and DHA are evident throughout the life course. Future research will include better identification of the determinants of variation of responses to increased intake of EPA and DHA; more in-depth dose–response studies of the effects of EPA and DHA; clearer identification of the specific roles of EPA, docosapentaenoic acid and DHA; testing strategies to enhance delivery of n-3 fatty acids to the bloodstream; and exploration of sustainable alternatives to fish-derived very long-chain n-3 fatty acids.
Psychopathy is an adult condition that incurs substantial societal and individual costs. Here we review neurocognitive and genetically informative studies that shed light on how and why this condition emerges. Children cannot present with psychopathy. However, the presence of callous–unemotional (CU) traits can distinguish a group of children who are at elevated risk of psychopathy in adulthood. These children display diminished empathy and guilt and show attenuated brain activation to distress cues in others. Genetically informative studies indicate that individual differences in CU traits show moderate-to-strong heritability, but that protective environmental factors can counter heritable risk. On the basis of the extant research findings, we speculate on what might represent the priorities for research over the next decade. We also consider the clinical implications of these research findings. In particular, we consider the importance of delineating what precisely works for children with CU traits (and their parents) and the ways in which intervention and prevention programs may be optimized to improve engagement as well as clinical outcomes.
Complex, diverse and rarely appearing without comorbidity, the autism spectrum disorders continue to be a source of research interest. With core symptoms variably impacting on social communication skills, the traditional focus of many research efforts has centred on the brain and how genetic and environmental processes impact on brain structure, function and/or connectivity to account for various behavioural presentations. Alongside emerging ideas on autistic traits being present in various clinical states, the autisms, and the overrepresentation of several comorbid conditions impacting on quality of life, other research avenues have opened up. The central role of the brain in relation to autism may be at least partially influenced by the functions of other organs. The gastrointestinal (GI) tract represents an important biological system pertinent to at least some autism. The notion of a gut–brain–behaviour axis has garnered support from various findings: an overrepresentation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Gaps remain in our knowledge of the functions of the GI tract linked to autism, specifically regarding mechanisms of action onward to behavioural presentation. Set however within the context of diversity in the presentation of autism, science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life.
This review aims at summarizing and discussing previous and recent findings concerning the cerebral manifestations of mitochondrial disorders (MIDs). MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) either already at onset or later in the course. After the muscle, the brain is the organ second most frequently affected in MIMODS. Cerebral manifestations of MIDs are variable and may present with or without a lesion on imaging or functional studies, but there can be imaging/functional lesions without clinical manifestations. The most well-known cerebral manifestations of MIDs include stroke-like episodes, epilepsy, headache, ataxia, movement disorders, hypopituitarism, muscle weakness, psychiatric abnormalities, nystagmus, white and gray matter lesions, atrophy, basal ganglia calcification, and hypometabolism on 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron-emission tomography. For most MIDs, only symptomatic therapy is currently available. Symptomatic treatment should be supplemented by vitamins, cofactors, and antioxidants. In conclusion, cerebral manifestations of MIDs need to be recognized and appropriately managed because they strongly determine the outcome of MID patients.
Objectives: Existing models of trichotillomania (TTM; hair pulling disorder) rely heavily on a biological predisposition or biological pathogenesis of the disorder, but fail to capture the specific neuropsychological mechanisms involved. The present systematic review aims to scope existing neuropsychological studies of TTM to explore gaps in current models. Methods: A systematic literature search was conducted to detect all published primary studies using neuropsychological and neuroimaging measures in a cohort of individuals experiencing TTM. Studies addressing neuropsychological function were divided into domains. Findings from imaging studies were considered within brain regions and across methodology. Results: Thirty studies with a combined 591 participants with TTM, 372 healthy controls and 225 participants in other types of control group were included. Sixteen studies investigated neuropsychological parameters, and 14 studies pursued neuroimaging technologies. Available studies that used neuropsychological assessments and reported a statistically significant difference between those with TTM and controls ranged in effect size from 0.25 to 1.58. All domains except verbal ability and visual ability reported a deficit. In neuroimaging studies, several structural and functional brain changes were reported that might be of significance to TTM. Only tentative conclusions can be made due to the use of multiple methodologies across studies, a major limitation to meaningful interpretations. Conclusions: Positive neuropsychological and neuroimaging results require replication, preferably with multi-site studies using standardized methodology. Increased standardized testing and analyses across the literature, as a whole, would improve the utility and interpretability of knowledge in this field. (JINS, 2018, 24, 188–205)
Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 539–550)
Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age. Similar patterns were observed for the concentrations of l-Asp in striatum, cerebral cortex and hippocampus, and l-arginine (l-Arg), l-Ala and l-valine (l-Val) in striatum. In addition, the concentrations of l-Asp, d-Ala, l-histidine, l-isoleucine (l-Ile), l-leucine (l-Leu), l-phenylalanine and l-Val were significantly higher in plasma of SPF mice when compared with those of GF mice. The concentrations of l-Arg, l-Gln, l-Ile and l-Leu were significantly higher in SPF than in GF mice, but those of d-Asp, d-serine and l-serine were higher in some brain regions of GF mice than in those of SPF mice. In conclusion, the concentration of amino acids in the host brain seems to be dependent on presence of the gut microbiota. Amino acid metabolism in the host brain may be modified by manipulating microbiota communities.
A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.
Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association.
1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test – Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes.
Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity.
The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.