ABSTRACT
Antidepressant drugs elicit different behavioral and neurochemical responses with age. In fact, the use of antidepressants during adolescence is associated with an increased risk of suicidal thinking, being the best pharmacological treatment during this critical period a matter of constant debate in terms of its risk-benefit outcome. In this regard, the present study compared the effects of nortriptyline (3-10 mg/kg, 7 days) on regulating different aspects of affective-like behavior by screening adolescent and adult Sprague-Dawley rats through several consecutive tests (forced-swim, open field, sucrose preference). Brains were later collected to evaluate hippocampal neurogenesis and mBDNF protein content as potential molecular correlates of the observed behavioral responses. The main results in adolescent rats showed that nortriptyline induced dose-dependent opposite effects: while 3 mg/kg decreased immobility and increased mBDNF (indicative of an antidepressant-like response), 10 mg/kg decreased exploratory time in the open field and mBDNF (suggestive of an anxiogenic-like response). These effects were not associated with changes in neurogenesis regulation. In adult rats, nortriptyline failed to modulate affective-like behavior or the neuroplasticity markers evaluated at the doses tested. In conclusion, clear behavioral and neurochemical differences were observed between adolescent and adult rats in response to nortriptyline treatment. Interestingly, while nortriptyline displayed an antidepressant-like potential at the lowest dose examined in adolescence, a higher dose shifted these results towards a negative outcome, thus reinforcing the need to extreme caution when considering this treatment for our younger population.
Subject(s)
Affective Symptoms/chemically induced , Antidepressive Agents/administration & dosage , Nortriptyline/administration & dosage , Adolescent , Adult , Affective Symptoms/pathology , Affective Symptoms/physiopathology , Age Factors , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain-Derived Neurotrophic Factor/metabolism , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Humans , Male , Neurogenesis/drug effects , Neurogenesis/physiology , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.
Subject(s)
Affective Symptoms/pathology , Affective Symptoms/physiopathology , Irritable Mood/physiology , Prefrontal Cortex/pathology , Adolescent , Affective Symptoms/diagnostic imaging , Atrophy/pathology , Child , Female , Humans , Magnetic Resonance Imaging , Male , Patient Acuity , Prefrontal Cortex/diagnostic imagingABSTRACT
While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress-related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post-traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.
Subject(s)
Adverse Childhood Experiences , Affective Symptoms/pathology , Medial Forebrain Bundle/pathology , Stress, Psychological/pathology , White Matter/pathology , Adult , Adult Survivors of Child Abuse , Affective Symptoms/diagnostic imaging , Diffusion Tensor Imaging , Female , Fornix, Brain/diagnostic imaging , Fornix, Brain/pathology , Humans , Male , Medial Forebrain Bundle/diagnostic imaging , Psychosocial Deprivation , Septal Nuclei/diagnostic imaging , Septal Nuclei/pathology , Socioeconomic Factors , Stress, Psychological/diagnostic imaging , White Matter/diagnostic imaging , Young AdultABSTRACT
Humans compute the anticipated reward value of stimuli in their environment in order to behave in an adaptive, goal-directed manner. This reward valuation ability is vital, and its disruption in a range of clinical populations has profound personal and social consequences. However, research has often failed to consider the reward-related functions of a central component of human emotion: conscious emotional experience. Alexithymia-a condition characterized by diminished conscious awareness of one's emotions-offers a unique opportunity to examine the link between emotional awareness and reward valuation. In the present study, we measured both acquired alexithymia and reward valuation ability in a large sample of patients with traumatic brain injuries (N = 112). Behavioral analyses provided evidence for a negative association between alexithymia and reward valuation ability. This association remained significant after controlling for several covariates in the model (anxiety, depression, posttraumatic stress disorder, and IQ). Voxel-based lesion-symptom mapping was carried out to identify brain regions-of-interest (ROIs) that, when damaged, lead to increased alexithymia and impaired reward valuation. Importantly, mediation models computed using the ROIs identified through the voxel-based lesion-symptom mapping revealed a specific indirect effect of left frontoinsular damage on impaired valuation that was mediated by increased levels of alexithymia. This indirect effect was not observed for any of the other candidate ROIs. The present study identifies a network of brain regions likely to be involved in the integration of subjective feelings and reward processes critical for the adaptive control of goal-directed behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Subject(s)
Affective Symptoms/psychology , Brain/pathology , Emotions/physiology , Frontal Lobe/pathology , Reward , Affective Symptoms/pathology , Brain Mapping , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Alexithymia is a trait involving difficulties processing emotions. Existing data suggest it is associated with violent offending. In violent offender programmes, therefore, violent offenders are screened for alexithymia and it is attended to if necessary. No studies have, however, examined alexithymia levels in nonviolent offenders and it is, therefore, unknown whether it is also a criminogenic factor in this population. AIMS: To investigate alexithymia levels among incarcerated nonviolent offenders and compare them with a community comparison group. METHOD: The 20-item Toronto Alexithymia Scale was used to compare the alexithymia levels of 67 incarcerated nonviolent offenders with a group of 139 people from the general public living in the community. RESULTS: Alexithymia levels did not differ between the groups. CONCLUSION: It appears that alexithymia is not a criminogenic factor for nonviolent offenders and screening of such offenders appears unnecessary.
Subject(s)
Affective Symptoms/diagnosis , Criminals/psychology , Emotions , Prisoners/psychology , Psychometrics/statistics & numerical data , Surveys and Questionnaires/standards , Adult , Affective Symptoms/pathology , Affective Symptoms/psychology , Aggression/psychology , Humans , Male , Middle Aged , Prisons , Reproducibility of ResultsABSTRACT
BACKGROUND: Alexithymia is a trait involving difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally orientated thinking (EOT). It is a risk factor for criminal behaviour. It is commonly assessed with the Toronto Alexithymia Scale (TAS-20), but the psychometrics of the TAS-20 have not been tested across the range of offender populations, and it has been suggested it might be unsuitable in incarcerated offenders. AIM: To establish the psychometrics of the TAS-20 among incarcerated offenders. METHODS: Factorial validity was examined using confirmatory factor analyses, and the invariance of this factor structure was tested against a published community sample. Reliability coefficients were calculated. RESULTS: One hundred and forty six incarcerated offenders were recruited. The factor structure of the TAS-20 was invariant across the samples. The intended factor structure composed of DIF, DDF and EOT factors performed well overall (with a reverse-scored method factor added), but six EOT items had low factor loadings. The total scale score and DIF and DDF subscales had acceptable reliability, but EOT did not. CONCLUSIONS: Our results suggest that the TAS-20 functions similarly in offender and community samples. Its total scale score, and DIF and DDF subscale scores can be used confidently, but the assessment of externally oriented thinking may not be adequate with this scale alone. In sum, the TAS-20 can facilitate robust assessment of alexithymia in closed criminal justice settings as well as in the wider community.
Subject(s)
Affective Symptoms/diagnosis , Criminal Behavior , Criminals , Expressed Emotion , Prisoners/psychology , Surveys and Questionnaires/standards , Adult , Affective Symptoms/pathology , Emotions , Female , Humans , Male , Psychometrics , Reproducibility of Results , Risk FactorsABSTRACT
Maternal stress during pregnancy and shortly thereafter is associated with altered offspring brain development that may increase risk of mood and anxiety disorders. Cortical gyrification is established during the prenatal period and the first 2 years of life and is altered in psychiatric disorders. Here, we sought to characterize the effects of perinatal stress exposure on offspring gyrification patterns and mood dysregulation in young adulthood. Participants included 85 young adults (56.5% women; 23-24 years) from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with perinatal stress data across four distinct timepoints and structural MRI data from young adulthood. Perinatal stress exposure was measured as maternal stress during first and second half of pregnancy, first 6 months, and 6-18 months after birth. Cortical gyrification and mood dysregulation were quantified using local gyrification index (LGI), computed with Freesurfer, and the Profile of Mood States questionnaire, respectively. Perinatal stress predicted cortical gyrification in young adulthood, and its timing influenced location, direction, and sex-specificity of effects. In particular, whereas early prenatal stress was associated with sex-dependent medium-to-large effects in large temporal, parietal, and occipital regions (f2 = 0.19-0.38, p < .001), later perinatal stress was associated with sex-independent small-to-medium effects in smaller, more anterior regions (f2 = 0.10-0.19, p < .003). Moreover, in females, early prenatal stress predicted higher LGI in a large temporal region, which was further associated with mood disturbance in adulthood (r = 0.399, p = .006). These findings point out the long-term implications of perinatal stress exposure for cortical morphology and mood dysregulation.
Subject(s)
Affective Symptoms , Cerebral Cortex , Prenatal Exposure Delayed Effects , Stress, Psychological/complications , Adult , Affective Symptoms/diagnostic imaging , Affective Symptoms/etiology , Affective Symptoms/pathology , Affective Symptoms/physiopathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Emotional Regulation/physiology , Female , Humans , Infant , Infant, Newborn , Longitudinal Studies , Magnetic Resonance Imaging , Male , Postpartum Period , Pregnancy , Prenatal Exposure Delayed Effects/diagnostic imaging , Prenatal Exposure Delayed Effects/etiology , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/physiopathology , Young AdultABSTRACT
BACKGROUND: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. METHODS: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. RESULTS: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. CONCLUSIONS: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.
Subject(s)
Affective Symptoms , Cerebral Cortex/pathology , Nerve Net/pathology , Personality , Adult , Affective Symptoms/diagnostic imaging , Affective Symptoms/epidemiology , Affective Symptoms/pathology , Affective Symptoms/physiopathology , Aged , Cerebral Cortex/diagnostic imaging , Female , Germany/epidemiology , Health Surveys , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/diagnostic imaging , Personality/physiologyABSTRACT
INTRODUCTION: Becker muscular dystrophy (BMD) results in decreased dystrophin with implications for mental health. METHODS: This is a retrospective case series of neurodevelopmental, behavioral, and emotional symptoms and respective pharmacotherapies of 70 patients with BMD. RESULTS: Fifty-four (77.1%) patients exhibited at least one symptom, and 19 (27.1%) patients exhibited four or more symptoms. The most prevalent symptoms were specific learning disabilities or special education needs (31.4%), inattention/hyperactivity (35.7%), language/speech delays (35.7%), and emotional or behavioral dysregulation (38.6%). Fisher's exact tests indicated that anxiety was more prevalent with mutations upstream of exon 30 (P = .049), but the prevalence of other symptoms did not differ with respect to mutation sites. Similarly, the number of symptoms individual patients with BMD exhibited did not differ with respect to mutation sites. Seventeen (24.3%) patients required pharmacotherapy to manage symptoms. DISCUSSION: Neurodevelopmental, behavioral, and emotional symptoms are prevalent in patients with BMD regardless of dystrophin gene mutation site.
Subject(s)
Affective Symptoms/etiology , Developmental Disabilities/etiology , Dystrophin/genetics , Muscular Dystrophy, Duchenne/complications , Adolescent , Affective Symptoms/pathology , Affective Symptoms/psychology , Anxiety/etiology , Anxiety/psychology , Attention Deficit Disorder with Hyperactivity/etiology , Attention Deficit Disorder with Hyperactivity/psychology , Child , Child, Preschool , Developmental Disabilities/psychology , Female , Humans , Infant , Language Development Disorders/etiology , Language Development Disorders/psychology , Learning Disabilities/etiology , Learning Disabilities/psychology , Male , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/psychology , Mutation , Prevalence , Retrospective Studies , Young AdultABSTRACT
Alexithymia has been extensively reported in studies of psychiatric patients. However, little attention has been paid regarding its occurrence in the context of patients with circumscribed prefrontal cortex lesions. Moreover, the neuro-cognitive impairments that lead to alexithymia remain unclear and limited numbers of studies have addressed these issues. The authors investigated the impact of prefrontal cortex lesions on alexithymia and its neuro-cognitive correlates in a population of 20 patients with focal frontal lesions, 10 patients with parietal lesions and 34 matched control participants. Alexithymia was screened using the Toronto Alexithymia Scale (TAS-20) and executive functions were assessed using a large battery of executive tasks that address inhibition, flexibility and the planning process. Results showed that patients with prefrontal cortex damage showed significantly increased difficulty in facets of identifying feelings (DIF) and externally oriented thinking (EOT) on TAS-20, compared to parietal patients and control participants. Moreover, both correlation and regression analysis revealed that higher alexithymia levels on the three facets of TAS-20 were consistently but differentially associated with impairment in inhibition, flexibility and planning tasks for frontal patients and both control groups. These findings provide clinical evidence of the implication of prefrontal cortex damage and executive control in alexithymia. Our results were also discussed in the light of the cognitive appraisal concept as a mechanism involved in emotion episode processing. This study suggests that increased neuropsychological attention should be directed to the relation between the neuro-cognitive model of executive functions and cognitive appraisal theory in processing emotion.
Subject(s)
Affective Symptoms/pathology , Prefrontal Cortex/pathology , Adult , Affective Symptoms/complications , Affective Symptoms/psychology , Executive Function , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Young AdultABSTRACT
Impaired processing of emotional signals is a core feature of frontotemporal dementia syndromes, but the underlying neural mechanisms have proved challenging to characterize and measure. Progress in this field may depend on detecting functional changes in the working brain, and disentangling components of emotion processing that include sensory decoding, emotion categorization and emotional contagion. We addressed this using functional MRI of naturalistic, dynamic facial emotion processing with concurrent indices of autonomic arousal, in a cohort of patients representing all major frontotemporal dementia syndromes relative to healthy age-matched individuals. Seventeen patients with behavioural variant frontotemporal dementia [four female; mean (standard deviation) age 64.8 (6.8) years], 12 with semantic variant primary progressive aphasia [four female; 66.9 (7.0) years], nine with non-fluent variant primary progressive aphasia [five female; 67.4 (8.1) years] and 22 healthy controls [12 female; 68.6 (6.8) years] passively viewed videos of universal facial expressions during functional MRI acquisition, with simultaneous heart rate and pupillometric recordings; emotion identification accuracy was assessed in a post-scan behavioural task. Relative to healthy controls, patient groups showed significant impairments (analysis of variance models, all P < 0.05) of facial emotion identification (all syndromes) and cardiac (all syndromes) and pupillary (non-fluent variant only) reactivity. Group-level functional neuroanatomical changes were assessed using statistical parametric mapping, thresholded at P < 0.05 after correction for multiple comparisons over the whole brain or within pre-specified regions of interest. In response to viewing facial expressions, all participant groups showed comparable activation of primary visual cortex while patient groups showed differential hypo-activation of fusiform and posterior temporo-occipital junctional cortices. Bi-hemispheric, syndrome-specific activations predicting facial emotion identification performance were identified (behavioural variant, anterior insula and caudate; semantic variant, anterior temporal cortex; non-fluent variant, frontal operculum). The semantic and non-fluent variant groups additionally showed complex profiles of central parasympathetic and sympathetic autonomic involvement that overlapped signatures of emotional visual and categorization processing and extended (in the non-fluent group) to brainstem effector pathways. These findings open a window on the functional cerebral mechanisms underpinning complex socio-emotional phenotypes of frontotemporal dementia, with implications for novel physiological biomarker development.
Subject(s)
Affective Symptoms/pathology , Brain Mapping , Emotions/physiology , Frontotemporal Dementia/psychology , Magnetic Resonance Imaging , Nerve Net/pathology , Affective Symptoms/etiology , Affective Symptoms/physiopathology , Aged , Aphasia, Primary Progressive/pathology , Aphasia, Primary Progressive/physiopathology , Autonomic Nervous System/physiopathology , Facial Expression , Female , Frontotemporal Dementia/classification , Frontotemporal Dementia/pathology , Frontotemporal Dementia/physiopathology , Heart Rate/physiology , Humans , Limbic System/pathology , Limbic System/physiopathology , Male , Middle Aged , Nerve Net/physiopathology , Neuropsychological Tests , Pupil/physiologyABSTRACT
In addition to the characteristic motor symptoms, Parkinson's disease (PD) often involves a constellation of sleep and mood symptoms. However, the mechanisms underlying these comorbidities are largely unknown. We have previously reconstructed gene networks in the striatum of a population of (C57BL/6J x A/J) F2 mice and associated the networks to sleep and affective phenotypes, providing a resource for integrated analyses to investigate perturbed sleep and affective functions at the gene network level. Combining this resource with PD-relevant transcriptomic datasets from humans and mice, we identified four networks that showed elevated gene expression in PD patients, including a circadian clock and mitotic network that was altered similarly in mouse models of PD. We then utilized multiple types of omics data from public databases and linked this gene network to postsynaptic dopamine signaling in the striatum, CDK1-modulated transcriptional regulation, and the genetic susceptibility of PD. These findings suggest that dopamine deficiency, a key aspect of PD pathology, perturbs a circadian/mitotic gene network in striatal neurons. Since the normal functions of this network were relevant to sleep and affective behaviors, these findings implicate that dysregulation of functional gene networks may be involved in the emergence of non-motor symptoms in PD. Our analyses present a framework for integrating multi-omics data from diverse sources in mice and humans to reveal insights into comorbid symptoms of complex diseases.
Subject(s)
Affective Symptoms/genetics , Corpus Striatum/pathology , Dopamine/deficiency , Gene Regulatory Networks/physiology , Parkinson Disease/genetics , Sleep/genetics , Affective Symptoms/pathology , Affective Symptoms/physiopathology , Animals , CDC2 Protein Kinase/metabolism , Circadian Clocks/genetics , Corpus Striatum/cytology , Corpus Striatum/physiopathology , Datasets as Topic , Disease Models, Animal , Dopaminergic Neurons/pathology , Gene Expression Profiling , Gene Expression Regulation/physiology , Genetic Predisposition to Disease , Humans , Male , Mice , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Transcription, GeneticABSTRACT
Past research suggests an association between reactive aggression and alexithymia, but neural mechanisms underlying this association remain unknown. Furthermore, the relationship between proactive aggression and alexithymia remains untested. This study aimed to: (1) test whether alexithymia is more related to reactive than proactive aggression; and (2) determine whether amygdala, insula, and/or anterior cingulate cortical (ACC) volume could be neurobiological mechanisms for this association. One hundred and fifty-six community males completed the Reactive-Proactive Aggression Questionnaire and the Toronto Alexithymia Scale. Amygdala, insula, and ACC volumes were assessed using MRI. Alexithymia was positively associated with reactive but not proactive aggression. Alexithymia was positively and bilaterally associated with amygdala and anterior cingulate volumes. Reactive aggression was positively associated with right amygdala volume. Controlling for right amygdala volume rendered the alexithymia-reactive aggression relationship non-significant. Results suggest that increased right amygdala volume is a common neurobiological denominator for both alexithymia and reactive aggression. Findings suggest that greater right hemisphere activation may reflect a vulnerability to negative affect, which in turn predisposes to experiencing negative emotions leading to increased aggression. Findings are among the first to explicate the nature of the alexithymia-aggression relationship, with potential clinical implications.
Subject(s)
Affective Symptoms/pathology , Affective Symptoms/psychology , Aggression/psychology , Amygdala/pathology , Magnetic Resonance Imaging/methods , Adult , Affective Symptoms/diagnostic imaging , Amygdala/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/pathology , Humans , Male , Organ Size , Psychiatric Status Rating Scales , Surveys and QuestionnairesABSTRACT
The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean ageâ¯=â¯25, SDâ¯=â¯5â¯years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025â¯mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6â¯h 30â¯m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (pâ¯<â¯.001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p'sâ¯>â¯.21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (pâ¯<â¯.05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression.
Subject(s)
Emotional Intelligence/physiology , Inflammation/pathology , Theory of Mind/physiology , Adult , Affective Symptoms/pathology , Cognition/physiology , Cross-Over Studies , Double-Blind Method , Emotions/physiology , Humans , Inflammation/metabolism , Interleukin-6/analysis , Interleukin-6/blood , Interpersonal Relations , Male , Typhoid-Paratyphoid Vaccines , VaccinationABSTRACT
ATP-sensitive potassium (KATP) channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a regulatory sulfonylurea receptor subunit (SUR1, SUR2A or SUR2B). Although Kir6.2 is widely distributed in the brain, the mechanisms that underlie the impact of Kir6.2 on emotional behavior are not yet fully understood. To clarify the role of Kir6.2 in emotional behavior, in the present study, we investigated the behavioral characteristics of Kir6.2-knockout (Kir6.2-/-) mice. Kir6.2-/- mice showed impaired general behavior in a locomotor activity test and open field test. In addition, anxiety-like behavior was observed in the open field test, elevated plus-maze test and light-dark test. In particular, excessive anxiety-like behavior was observed in female Kir6.2-/- mice. Moreover, we investigated whether Kir6.2 is expressed on monoamine neurons in the brain. Immunohistochemical studies showed that Kir6.2 was co-localized with tryptophan hydroxylase (TPH), a marker of serotonergic neurons, in dorsal raphe nuclei. Kir6.2 was also co-localized with tyrosine hydroxylase (TH), a marker of dopaminergic/noradrenergic neurons, in the ventral tegmental area and locus coeruleus. Next, we checked the protein levels of TH and TPH in the midbrain. Interestingly, TPH expression was significantly elevated in female Kir6.2-/- mice. These results suggest that Kir6.2 in monoamine neurons, especially serotonergic neurons, could play a key role in emotional behavior.
Subject(s)
Affective Symptoms/genetics , Affective Symptoms/pathology , Biogenic Monoamines/metabolism , Brain/pathology , Neurons/metabolism , Potassium Channels, Inwardly Rectifying/deficiency , Adaptation, Ocular/genetics , Animals , Disease Models, Animal , Exploratory Behavior/physiology , Female , Locomotion/physiology , Male , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Potassium Channels, Inwardly Rectifying/genetics , Swimming/physiologyABSTRACT
OBJECTIVES: Immunological/inflammatory processes have been proposed to play an important role in the pathophysiology of mood disorders, including bipolar disorder (BD). The present study aimed to examine the influence of immune activation, measured on the basis of inflammatory markers, on the course of illness, proxied by the number of affective episodes, in patients with BD. METHODS: We investigated the relationship between high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6), two inflammatory markers and characteristics of course of illness (e.g. number of affective episodes, depressive and manic symptoms) amongst a group of 190 individuals with BD. RESULTS: Among females with BD, there was a positive correlation between levels of hsCRP and the number of manic and depressive episodes. Moreover, levels of hsCRP and IL-6 were positively correlated with current manic symptoms, as measured by Young-Mania-Rating-Scale. There were no significant correlations between levels of the foregoing inflammatory markers, and manic and depressive symptoms in male individuals with BD. Furthermore, compared to their untreated counterparts, female patients treated with lithium demonstrated higher levels of hsCRP and male patients treated with atypical antipsychotics lower levels of hsCRP, respectively. CONCLUSIONS: Our results are suggesting that the association between inflammatory state and affective response in patients with BD may be gender-dependent. A future research would be to evaluate whether or not these gender differences can be observed in other inflammatory pathways associated with BD.
Subject(s)
Affective Symptoms/blood , Bipolar Disorder/blood , Bipolar Disorder/psychology , Inflammation/blood , Inflammation/psychology , Adult , Affective Symptoms/pathology , Antipsychotic Agents/administration & dosage , Biomarkers/blood , Bipolar Disorder/drug therapy , Bipolar Disorder/pathology , C-Reactive Protein/metabolism , Female , Humans , Inflammation/pathology , Interleukin-6/blood , Male , Middle Aged , Mood Disorders/blood , Mood Disorders/pathology , Sex FactorsABSTRACT
Alexithymia refers to deficiencies in identifying and expressing emotions. This might be related to changes in structural brain volumes, but its neuroanatomical basis remains uncertain as studies have shown heterogeneous findings. Therefore, we conducted a parametric coordinate-based meta-analysis. We identified seventeen structural neuroimaging studies (including a total of 2586 individuals with different levels of alexithymia) investigating the association between gray matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital frontal cortex and striatum were consistently smaller in people with high levels of alexithymia. These areas are important for emotion perception and emotional experience. Smaller volumes in these areas might lead to deficiencies in appropriately identifying and expressing emotions. These findings provide the first quantitative integration of results pertaining to the structural neuroanatomical basis of alexithymia.
Subject(s)
Affective Symptoms/pathology , Brain/pathology , Affective Symptoms/diagnostic imaging , Brain/diagnostic imaging , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Magnetic Resonance Imaging , NeuroimagingABSTRACT
Pain remains highly prevalent in HIV-seropositive (HIV+) patients despite their well-suppressed viremia with combined antiretroviral therapy. Investigating brain abnormalities within the pain matrix, and in relation to pain symptoms, in HIV+ participants may provide objective biomarkers and insights regarding their pain symptoms. We used Patient-Reported Outcome Measurement Information System (PROMIS®) pain questionnaire to evaluate pain symptoms (pain intensity, pain interference and pain behavior), and structural MRI to assess brain morphometry using FreeSurfer (cortical area, cortical thickness and subcortical volumes were evaluated in 12 regions within the pain matrix). Compared to seronegative (SN) controls, HIV+ participants had smaller surface areas in prefrontal pars triangularis (right: p = 0.04, left: p = 0.007) and right anterior cingulate cortex (p = 0.03) and smaller subcortical regions (thalamus: p ≤ 0.003 bilaterally; right putamen: p = 0.01), as well as higher pain scores (pain intensity-p = 0.005; pain interference-p = 0.008; pain-behavior-p = 0.04). Furthermore, higher pain scores were associated with larger cortical areas, thinner cortices and larger subcortical volumes in HIV+ participants; but smaller cortical areas, thicker cortices and smaller subcortical volumes in SN controls (interaction-p = 0.009 to p = 0.04). These group differences in the pain-associated brain abnormalities suggest that HIV+ individuals have abnormal pain responses. Since these abnormal pain-associated brain regions belong to the affective component of the pain matrix, affective symptoms may influence pain perception in HIV+ patients and should be treated along with their physical pain symptoms. Lastly, associations of lower pain scores with better physical or mental health scores, regardless of HIV-serostatus (p < 0.001), suggest adequate pain treatment would lead to better quality of life in all participants.
Subject(s)
Brain/pathology , HIV Infections/complications , HIV Infections/pathology , Pain/etiology , Affective Symptoms/etiology , Affective Symptoms/pathology , Female , HIV Infections/psychology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pain/pathologyABSTRACT
OBJECTIVE: Affective disorders are prevalent in different somatic conditions and influence somatic symptom bother and quality of life. Mood and anxiety disorders impact patients' compliance and adherence to treatment. This systematic review summarizes published studies on affective complaints in patients with oropharyngeal dysphagia (OD) in order to determine the quality of studies concerning any association of OD with symptoms of depression and/or anxiety. METHODS: A literature search was carried out using electronic databases Embase, Medline, Web-of-science, PsycINFO, Cochrane Library, and Google scholar. Two reviewers made the preselecting cut by screening all articles on title and abstract and independently screened the full texts of this initial set of articles. Methodological quality of the studies that met the inclusion criteria was assessed independently. RESULTS: Twenty-six articles were included in the analysis after full-text screening and by applying the inclusion and exclusion criteria. All studies concluded that symptoms of depression were associated with impaired swallowing function, and 9 out of 12 studies concluded that symptoms of anxiety were associated with functional impairment of swallowing. The reviewers found heterogeneous outcomes and methodological limitations, which prevented data from pooling. CONCLUSION: Although no meta-analytic conclusions can be drawn, it appears that symptoms of anxiety and depression are common in OD. Caregivers have to be aware of this in order to detect affective comorbidity. Given that affective conditions influence patients' treatment adherence and compliance, integrated care approaches should be advocated in case of comorbidity. Studies on treatment effect are lacking and well-designed prospective research is needed.
Subject(s)
Affective Symptoms/etiology , Deglutition Disorders/complications , Depression/etiology , Affective Symptoms/pathology , Deglutition Disorders/physiopathology , Humans , Prospective StudiesABSTRACT
OBJECTIVE: We examined the complex relationship between lesion location, symptoms of depression (affective and apathetic), and monoamine dysfunction after stroke. METHODS: Magnetic resonance imaging was performed on 48 post-stroke patients that had been assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. Noradrenalin (NA), dopamine (DA), their metabolites, and a metabolite of serotonin (5-HT) were measured using 24-h urine samples, and 5-HT and 3-methoxy-4-hydroxyphenylglycol were measured using blood samples. We developed a statistical parametric map that displayed the associations between lesion location and both positive and negative alterations of monoamines and their metabolites. RESULTS: Multivariate analysis indicated that basal ganglia lesions and 5-HT showed relationships with affective symptoms, whereas homovanillic acid was related to apathetic symptoms. Univariate analysis showed no such relationships. However, decreases in NA and DA and increases in NA and DA turnover were related to lesions in the brainstem, whereas increases in NA and DA as well as decreases in NA and DA turnover were related to cortical and/or striatum lesions. 5-HT turnover data showed a pattern opposite to that seen for NA and DA turnover. CONCLUSIONS: Monoaminergic neuronal pathways are controlled by both receptor-mediated feedback mechanisms and turnover; thus, depletion of monoamines is not the only cause of depression and apathy. Moreover, the monoamine neuronal network might be divided into two branches, catecholamine (NA and DA) and 5-HT, both of which are anatomically and functionally interconnected and could respectively influence apathetic and affective symptoms of depression.