Neurobiological Changes Research Articles

The emotional pathway to parenthood: Parental mentalizing mediates the association between alexithymia and parental emotion regulation in the transition to parenthood

Becoming a parent is perhaps one of the most profound processes in the lives of individuals, and it entails significant psychological, neurobiological, and hormonal changes designed to facilitate successful caretaking. It is considered a highly challenging emotional transitional experience for most parents both as individuals and couples, accompanied with elevated levels of role overload and stress. Therefore, parents’ self emotion-regulation within the parenting context plays an important role in the transition to parenthood. Unfortunately, parents’ own self-regulation within the context of parenting is largely overlooked. The aim of the current investigation was to explore whether parental self emotion-regulation at six months can be predicted from a prenatally measured trait-like capacity for emotional awareness and labeling—alexithymia. Moreover, this study examined the mediation role parental mentalizing may play in this longitudinal association, while accounting for situational emotional functioning in the form of parental depression. Importantly, this mediation model was tested using an APIM model, considering he mutual influences of both partners on the other. The sample involved 104 community-based couples in the transition to parenthood (prenatally and at six-months). Results showed adults’ alexithymia, assessed prenatally, predicted parental mentalizing, which, in turn, predicted the parent's ability to regulate one own self in challenging times of parental distress, above and beyond postnatal depression. Moreover, this study revealed important dyadic associations between both parents, highlighting the importance of examining parental capacities and functioning within a systemic framework. The empirical and clinical implications of these findings are discussed.

Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm.

The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.

Decreased gray matter volume in regions associated with affective pain processing in unmedicated individuals with nonsuicidal self-injury

Nonsuicidal self-injury (NSSI) has been consistently associated with a reduced aversion to physical pain. Yet, little research has been done to investigate the brain structures related to pain in individuals with NSSI. This study examined gray matter volume patterns of pain processing regions in participants engaging in NSSI (n = 63) and age-, sex-, and handedness-matched healthy controls (n = 63). Voxel-based morphometry was performed to explore gray matter volume in regions of interest (ROIs) and partial correlation analyses were conducted to identify their associations with the frequency, versatility, duration, functions, and pain intensity of self-injury. As a result, significant volume decreases were found in the right anterior insula, bilateral secondary somatosensory cortex (SII), and left inferior frontal gyrus. Moreover, individuals with smaller anterior insula and SII volume showed a higher likelihood of endorsing affect-regulation and sensation-seeking functions of NSSI, as well as engaging in self-injury with a greater perceived intensity of pain. Our results provide the first empirical evidence that individuals with NSSI may exhibit distinct characteristics in brain regions associated with the affective component of pain processing. These neurobiological changes may be associated with their maladaptive response to noxious and painful NSSI experiences.

Effects of Psychotherapy on Glutamatergic Neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery.

Neurobiology of pregnancy and the postpartum period in the common marmoset

Preclinical data suggest pregnancy is associated with neurobiological changes in brain regions relevant to maternal behavior. Unfortunately, there is an absence of basic neurobiological information about the effects of pregnancy and the postpartum on the human brain. Moreover, we lack relevant studies in non-human primates that track changes in brain systems across pregnancy and parturition and their associations with maternal behavior. To bridge this gap, we examined the potential relationship between brain structure and function, and maternal behavior across pregnancy in the common marmoset (Callithrix jacchus). Eight nulliparous females (4 pregnant; 4 non-pregnant controls) were studied at four time points: pre-pregnancy baseline, gestation 1 (50-70days), gestation 2 (105-125days), and postpartum (3-14days). Infant-directed behavior was assessed using a custom-built T-Maze designed to assess responsiveness towards two infants. The number of times the female approached either infant and the overall pattern of movement was tracked using EthoVision and compared to non-pregnant multiparous and postpartum controls. Structural (T1-weighted and DTI) and functional (awake resting-state) MRI scans were collected on a 7 T Bruker scanner. Our data thus far show that among nulliparous females, infant-directed behavior decreased across gestation. During the postpartum period, the now primiparous females showed behavior equivalent to postpartum controls. Our preliminary observations support previous findings of infant avoidance in nulliparous females prior to parturition and increased infant responsiveness during the postpartum. Future analysis of our multimodal neuroimaging data will help elucidate the relationship between pregnancy and the postpartum, maternal behavior, and putative changes in the brain.

Running from stress: a perspective on the potential benefits of exercise-induced small extracellular vesicles for individuals with major depressive disorder.

Aerobic exercise promotes beneficial effects in the brain including increased synaptic plasticity and neurogenesis and regulates neuroinflammation and stress response via the hypothalamic-pituitary-adrenal axis. Exercise can have therapeutic effects for numerous brain-related pathologies, including major depressive disorder (MDD). Beneficial effects of aerobic exercise are thought to be mediated through the release of "exerkines" including metabolites, proteins, nucleic acids, and hormones that communicate between the brain and periphery. While the specific mechanisms underlying the positive effects of aerobic exercise on MDD have not been fully elucidated, the evidence suggests that exercise may exert a direct or indirect influence on the brain via small extracellular vesicles which have been shown to transport signaling molecules including "exerkines" between cells and across the blood-brain barrier (BBB). sEVs are released by most cell types, found in numerous biofluids, and capable of crossing the BBB. sEVs have been associated with numerous brain-related functions including neuronal stress response, cell-cell communication, as well as those affected by exercise like synaptic plasticity and neurogenesis. In addition to known exerkines, they are loaded with other modulatory cargo such as microRNA (miRNA), an epigenetic regulator that regulates gene expression levels. How exercise-induced sEVs mediate exercise dependent improvements in MDD is unknown. Here, we perform a thorough survey of the current literature to elucidate the potential role of sEVs in the context of neurobiological changes seen with exercise and depression by summarizing studies on exercise and MDD, exercise and sEVs, and finally, sEVs as they relate to MDD. Moreover, we describe the links between peripheral sEV levels and their potential for infiltration into the brain. While literature suggests that aerobic exercise is protective against the development of mood disorders, there remains a scarcity of data on the therapeutic effects of exercise. Recent studies have shown that aerobic exercise does not appear to influence sEV size, but rather influence their concentration and cargo. These molecules have been independently implicated in numerous neuropsychiatric disorders. Taken together, these studies suggest that concentration of sEVs are increased post exercise, and they may contain specifically packaged protective cargo representing a novel therapeutic for MDD.

Maternal anxiety-driven modulation of fetal limbic connectivity designs a backbone linking neonatal brain functional topology to socio-emotional development in early childhood.

A link between maternal anxiety during pregnancy and adverse socio-emotional outcomes in childhood has been consistently sustained on the very early neurodevelopmental alteration of structural pathways between fetal limbic and cortical brain regions. In this study, we provide follow-up evidence for a feed-forward model linking (i) maternal anxiety, (ii) fetal functional neurodevelopment, (iii) neonatal functional network organization with (iv) socio-emotional neurobehavioral development in early childhood. Namely, we investigate a sample of 16 mother-fetus dyads and show how a maternal state-trait anxiety profile with pregnancy-specific worries can significantly influence functional synchronization patterns between regions of the fetal limbic system (i.e., hippocampus and amygdala) and the neocortex, as assessed through resting-state functional magnetic resonance imaging. Generalization of the findings was supported by leave-one-out cross-validation. We further show how this maternal-fetal cross-talk propagates to functional network topology in the neonate, specifically targeting connector hubs, and further maps onto socio-emotional profiles, assessed through Bayley-III socio-emotional scale in early childhood (i.e., in the 12-24 months range). Based on this evidence, we put forward the hypothesis of a "Maternal-Fetal-Neonatal Anxiety Backbone", through which neurobiological changes driven by maternal anxiety could trigger a divergence in the establishment of a cognitive-emotional development blueprint, in terms of the nascent functional homeostasis between bottom-up limbic and top-down higher-order neuronal circuitry.

Depression in older patients with dementia during COVID‐19 pandemics in Romania ‐ a geriatric center perspective

AbstractBackgroundA convincing body of evidence identifies depression as a risk factor for later life dementia, whereas later life depression should be considered as a prodrome for dementia. COVID‐19 pandemics highly affected elderly, and those suffering from dementia were among the most vulnerable populations to a severe evolution of SARS‐CoV2 infection as well as impacted by social isolation.MethodWe analyzed the association of depression in a study group of 162 geriatric patients, admitted due to complains of neurocognitive and psychiatric symptoms but also to other comorbidities, hospitalized in 2020‐2021 in our Geriatric Clinic after the pandemic was declared. All patients were evaluated using standard Mini Mental State Evaluation (MMSE) scale, Clock‐ Drawing Test (CDT) and Geriatric Depression Scale (GDS). Native cerebral CT‐scan imaging was used to assess if any neurobiological changes occurred.ResultThe incidence of dementia was 72.8% in the study group of 162 consecutive hospital admissions in the geriatric department. Out of the 118 cognitively impaired patients (out of which 9 were previously diagnosed with Alzheimer Disease), 73.7% had associated depression; other prevalent comorbidities in the geriatric lot were cardiovascular, neurologic, metabolic and musculoskeletal disorders. The relative risk of depression associated to dementia was 1.75. The complex relationship linking dementia and depression has also neuropathological underlying mechanisms‐ decreased cortical thickness and white matter loss were associated with both depressive symptoms and impairment of cognitive functions. In our study the majority of the patients (62.3%) presented structural abnormalities of different categories in cerebral CT‐scan imaging.ConclusionThis high incidence reported on the association between dementia and depression in geriatric hospitalized patients is in line with the results of other studies, supporting the idea of standardizing a clinical assessment protocol for evaluating both cognitive dysfunction and depression in all elderly patients and monitoring their evolution. COVID‐19 conditions isolating elderly and restricting their access to medical services increased the risk of worsening their cognitive status and mental health. As the effective treatments for dementia remain scarce, clinicians could use a preventive approach by identification of high‐risk individuals ‐ one of the most relevant dementia risk factors being depression.

Adolescent exposure to the Spice/K2 cannabinoid JWH-018 impairs sensorimotor gating and alters cortical perineuronal nets in a sex-dependent manner

The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.

Maternal nicotine intoxication before pregnancy induces depressive- and anxiety-like behaviors as well as cognitive deficits in male offspring and correlates with neurobiological changes.

Maternal nicotine use has been suggested to affect the behavior of children and is linked to changes in neurological systems; however, the specific mechanism is yet to be understood. Mice were used to establish a maternal nicotine intoxication model. At postnatal day 60 (adolescent stage), male offspring were tested for behavioral tasks including sucrose preference, open field, elevated plus maze, light/dark box, object recognition, Morris water maze (MWM), and forced swimming. Enzyme-linked immunoassays were used to measure plasma concentrations of neurotransmitters including norepinephrine, dopamine, serotonin, and corticosterone. Serotonin transporter (Sert), brain-derived neurotrophic factor (Bdnf), cAMP response element binding protein (Creb), and phosphorylated (p)Creb mRNA levels were measured using quantitative real-time polymerase chain reaction. Male offspring of nicotine-intoxicated dams had significantly reduced sucrose preference, mobility time in the forced swimming test, and locomotor and exploratory activities. Offspring in the maternal nicotine intoxication group showed increased signs of depressive- and anxiety-like behavior. Recognition memory in the MWM was compromised in these animals. The hippocampal and prefrontal cortical regions showed significant changes in Bdnf, pCreb, and Sert gene expression, whereas CREB mRNA levels were unaffected. Moreover, compared to the controls, neurogenesis and neuronal viability were also reduced in these animals. Prenatal nicotine exposure might affect the hypothalamic-pituitary-adrenal axis and reduce neurogenesis, potentially leading to depressive-like behaviors and cognitive deficiencies in male offspring.

A pharmacological challenge paradigm to assess neural signatures of script-elicited acute dissociation in women with post-traumatic stress disorder.

There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation. To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories. Women with post-traumatic stress disorder (n = 47) and a history of interpersonal childhood trauma underwent a within-participant, placebo-controlled pharmacological challenge paradigm (4.0 mg reboxetine versus placebo) employing script-driven imagery (traumatic versus neutral autobiographical memory recall). Script-elicited brain activation patterns (measured via functional magnetic resonance imagery) were analysed by means of whole-brain analyses and a pre-registered region of interest (i.e. amygdala). Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks. Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.

Neurobiological mechanisms involved in maternal deprivation-induced behaviours relevant to psychiatric disorders.

Parental care is essential for proper development of stress response and emotion-related behaviours. Epidemiological studies show that parental loss in childhood represents a major risk factor for the development of mental disorders throughout the lifespan, including schizophrenia, depression, and anxiety. In most mammalian species, the mother is the main source of care and maternal behaviours regulate several physiological systems. Maternal deprivation (DEP) for 24 h is a paradigm widely used to disinhibit the hypothalamic-pituitary-adrenal axis response to stress during the stress hyporesponsive period. In this mini-review we will highlight the main DEP-induced neurobiological and behavioural outcomes, including alterations on stress-related hormones, neurogenesis, neurotransmitter/neuromodulatory systems and neuroinflammation. These neurobiological changes may be reflected by aberrant behaviours, which are relevant to the study of mental disorders. The evidence indicates that DEP consequences depend on the sex, the age when the DEP takes place and the age when the animals are evaluated, reflecting dynamic plasticity and individual variability. Individual variability and sex differences have a great relevance for the study of biological factors of stress resilience and vulnerability and the DEP paradigm is a suitable model for evaluation of phenotypes of stress- and emotion-related psychopathologies.

Reduced olfactory bulb volume and olfactory sulcus depth in obsessive compulsive disorder

Many studies have shown that limbic system abnormalities are seen in obsessive-compulsive disorder (OCD), but the neurobiological changes in OCD are still unclear. Moreover, olfactory bulb volume (OBV) and its association with symptom severity have not been yet investigated in patients with OCD. This is the first study on OBV and olfactory sulcus depth (OSD) values in OCD patients, to the best of our knowledge. Between January 2018 and March 2022, 25 patients with OCD and 26 healthy controls with brain magnetic resonance imaging (MRI) were included. Detailed disease history of OCD patients was taken, and Yale-Brown obsessive-compulsive scale (YBOCS) was applied. The mean age of the patient group was 33.40±9.58, the mean age of the control group was 32.84±8.01. LOBV, ROBV, TOBV, and LOSD in the patient group were significantly lower than in the control group (p=.013, p=.005, p=.001, p=.015, respectively). ROBV and TOBV were negatively correlated with YBOCS total and subscale scores. A negative correlation was found between ROBV and TOBV and disease duration (r=-0.749 and r=-0.640, respectively). The negative correlation of ROBV and TOBV values with disease duration and disease severity can be used to monitor the neurodegenerative process of OCD disease.

Targeting the Arginine Vasopressin V1b Receptor System and Stress Response in Depression and Other Neuropsychiatric Disorders.

A healthy stress response is critical for good mental and overall health and promotes neuronal growth and adaptation, but the intricately balanced biological mechanisms that facilitate a stress response can also result in predisposition to disease when that equilibrium is disrupted. The hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system plays a critical role in the body's response and adaptation to stress, and vasopressinergic regulation of the HPA axis is critical to maintaining system responsiveness during chronic stress. However, exposure to repeated or excessive physical or emotional stress or trauma can shift the body's stress response equilibrium to a "new normal" underpinned by enduring changes in HPA axis function. Exposure to early life stress due to adverse childhood experiences can also lead to lasting neurobiological changes, including in HPA axis function. HPA axis impairment in patients with depression is considered among the most reliable findings in biological psychiatry, and chronic stress has been shown to play a major role in the pathogenesis and onset of depression and other neuropsychiatric disorders. Modulating HPA axis activity, for example via targeted antagonism of the vasopressin V1b receptor, is a promising approach for patients with depression and other neuropsychiatric disorders associated with HPA axis impairment. Despite favorable preclinical indications in animal models, demonstration of clinical efficacy for the treatment of depressive disorders by targeting HPA axis dysfunction has been challenging, possibly due to the heterogeneity and syndromal nature of depressive disorders. Measures of HPA axis function, such as elevated cortisol levels, may be useful biomarkers for identifying patients who may benefit from treatments that modulate HPA axis activity. Utilizing clinical biomarkers to identify subsets of patients with impaired HPA axis function who may benefit is a promising next step in fine-tuning HPA axis activity via targeted antagonism of the V1b receptor.

MP30-13 EFFECTS OF MARRIAGE AND SOCIAL DETERMINANTS OF HEALTH ON TOTAL TESTOSTERONE LEVEL

You have accessJournal of UrologyCME1 Apr 2023MP30-13 EFFECTS OF MARRIAGE AND SOCIAL DETERMINANTS OF HEALTH ON TOTAL TESTOSTERONE LEVEL William Shyr, Jonathan Davilla, and Darius Paduch William ShyrWilliam Shyr More articles by this author , Jonathan DavillaJonathan Davilla More articles by this author , and Darius PaduchDarius Paduch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Effects of social determinants of health (SDOH) on male reproductive health are poorly understood, but they play an important role in cardiovascular health in men. In this study, we wanted to answer if marital status, education, and income, in addition to biological factors, affect total testosterone (TT) levels. METHODS: Data from the 2013-2016 NHANES survey were included. TT was measured using liquid chromatography mass spectrometry certified by CDC. Subjects 18-79 years old were evaluated in the study. The effect of marital status, the ratio of family income to poverty (PIR), education level, current use of tobacco, presence of diabetes mellitus (DM), coronary artery disease (CAD), hypercholesterolemia, hypertension, age, and body mass index (BMI) on TT were evaluated using multivariate and univariate analysis. The living with a partner group included men living with a partner or married; the single group included widowed, divorced, separated, or never-married men. TT levels are reported as mean values. P-value <0.05 was considered significant. RESULTS: Data from 4,224 men were included. Men living with a partner had significantly lower TT (400 ng/dL) than single men (470 ng/dL) (p<0.0001). Men with at least a college degree had lower TT (415 ng/dL) compared to men without a high school diploma (438 n/dL) (p=0.04). Men aged 18-79 with income below the median PIR (3.09) had higher TT (p=0.009; univariate model). Older men (60-70 yo) with the lowest income (PIR<1) had lower TT (383 ng/dL) than men with higher income (417 ng/dL) (p=0.048). In the multivariate analysis, cohabitation had the largest negative effect size on TT (p<0.001) compared to that of BMI (p<0.001), DM (p=0.02), and hypercholesterolemia (p<0.001), but the effect of education and PIR was not significant. Current smokers had higher TT than never-smokers (p=0.03). CONCLUSIONS: SDOH was a significant predictor of TT. Married men, men with at least a college education, or men with higher income had significantly lower TT levels. Epidemiological and biological factors of our findings have to be further investigated; a sedentary lifestyle, diet, and neurobiological changes related to cohabitation may be possible explanations. Maintaining an active and healthy lifestyle for all, especially married men, is important to sustain optimal TT. Source of Funding: Fracchia Research Scholarship © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e395 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Shyr More articles by this author Jonathan Davilla More articles by this author Darius Paduch More articles by this author Expand All Advertisement PDF downloadLoading ...

Effects of Caloric Restriction on Spatial Object Recognition Memory, Hippocampal Neuron Loss and Neuroinflammation in Aged Rats

Age-related neurobiological changes significantly affect hippocampal structure and function, such that the main cognitive impairments associated with aging are related to the integrity of this brain structure, including the deterioration in spatial object recognition (SOR) memory. Previous studies have shown that intrinsic factors such as neuroinflammation, as well as lifestyle factors such as diet, can affect aging-associated brain functions and cognitive performance. In this regard, caloric restriction (CR) produces beneficial effects on health and life expectancy, although its ability to slow down age-dependent effects on cognitive decline and hippocampus (HPC) functioning remains unclear. Therefore, we set out to evaluate the effects of CR on SOR memory in aged male Wistar rats, as well as those on hippocampal neuron loss, neurogenesis and inflammation. The data show that CR in aged rats attenuates the decline in SOR memory, age-associated hippocampal neuron loss, and age-dependent microglial activation. Furthermore, we found a significant reduction in neurogenesis in the dentate gyrus of the old animals relative to adult rats. These findings support the positive effect of CR on SOR memory, suggesting that it dampens hippocampal neuronal loss and reduces proinflammatory activity.

Negative association between non-suicidal self-injury in adolescents and default mode network activation during the distraction blocks of a rumination task.

Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI. We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast. Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum. Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change.

Amphetamine-induced prolonged disturbances in tissue levels of dopamine and serotonin in the rat brain

BackgroundA hallmark of psychostimulants is the persistence of neurobiological changes they produce. The difficulty in reversing long-time effects of psychostimulants use is why addiction therapy is so ineffective. This study aimed to look for such drug-induced changes that can be detected even after many weeks of abstinence.MethodsRats were given 12 doses of amphetamine (Amph) at 1.5 mg/kg. The rewarding effect of Amph was assessed using ultrasonic vocalization. After 14 and 28 days of abstinence, tissue levels of dopamine (DA), serotonin (5-HT), and their metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (Acb), dorsomedial (CPuM), and dorsolateral (CPuL) striatum.ResultsAfter 28 days of abstinence, DA levels were increased in the dorsal striatum while 5-HT levels were decreased in all brain regions studied. The opposite direction of changes in DA and 5-HT tissue levels observed in the dorsal striatum may be related to the changes in the emotional state during abstinence and may contribute to the incubation of craving and relapses. Tissue levels of 5-HT and DA showed intra- and inter-structural correlations, most pronounced after 14 days of abstinence. Most of them were absent in the control group (ctrl), which may indicate that their appearance was related to the changes induced by earlier Amph administration. We did not find any associations between reward sensitivity and the persistence of Amph-induced neurochemical disturbances.ConclusionsAdministration of 12 moderate doses of Amph causes prolonged changes in DA and 5-HT tissue levels. The direction and severity of the changes are dependent on the brain region and the neurotransmitter studied.

Altered Postcentral Connectivity after Sleep Deprivation Correlates to Impaired Risk Perception: A Resting-State Functional Magnetic Resonance Imaging Study.

Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions' communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired risk perception. Nineteen healthy male adults were recruited and underwent resting-state functional magnetic resonance imaging during a state of rested wakefulness and after nearly 36 h of total SD. They then completed the balloon analog risk task, which was used to measure the risk perception ability of risky decision-making. Regional homogeneity (ReHo) and voxel-wise functional connectivity were used to investigate neurobiological changes caused by SD. Correlation analysis was used to investigate the relationship between changes in ReHo, function, and risk perception. At the behavioral level, risk perception decreased after 36 h of SD. At the neural level, SD induced a significant increase in ReHo in the right postcentral gyrus and was positively correlated with risk perception changes. The functional connectivity between the right postcentral gyrus, left medial temporal gyrus, and right inferior temporal gyrus was enhanced. Critically, increased right postcentral gyrus and right inferior temporal gyrus connectivity positively correlated with changes in risk perception. SD impairs the risk perception associated with altered postcentral connectivity. The brain requires more energy to process and integrate sensory and perceptual information after SD, which may be one possible reason for decreased risk perception ability after SD.

Downregulation of cyclic adenosine monophosphate levels in leukocytes of hibernating captive black bears is similar to reported cyclic adenosine monophosphate findings in major depressive disorder.

Cyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation. To compare cAMP levels between human MDD and mammalian hibernation and to investigate whether cAMP downregulation is another state-dependent neurobiological finding, we measured cAMP concentrations in lysed leukocytes, plasma, and serum in serial blood specimens from nine female captive black bears (Ursus americanus; CBBs), and cortisol levels in serum from 10 CBBs. Cortisol levels were significantly higher during hibernation in CBBs, confirming previous findings in hibernating black bears and similar to findings in humans with MDD. cAMP levels were significantly lower during hibernation versus active states (pre-hibernation and exit from hibernation) and were similar to the cAMP downregulation reported in MDD patients versus euthymic patients or controls. cAMP level changes during the different states (hibernation, pre-hibernation, active) confirm their state-dependent status. These findings are similar to the neurobiological findings associated with the hypometabolism (metabolic depression) observed during mammalian hibernation and reported during MDD. A sudden increase in cAMP levels was observed before entrance into pre-hibernation and during exit from hibernation. Further investigation is suggested into the possible role of elevated cAMP levels in initiation of the chain reaction of changes in gene expression, proteins, and enzymes leading to the suppression of mitochondrial metabolism and to low ATP turnover. This process leads to hypometabolism, the old adaptive mechanism that is used by organisms for energy preservation and is associated with both mammalian hibernation and human MDD.