Prefrontal Cortex Volume Research Articles

Association of disease course and brain structural alterations in major depressive disorder.

The investigation of disease course-associated brain structural alterations in Major Depressive Disorder (MDD) have resulted in heterogeneous findings, possibly due to low reliability of single clinical variables used for defining disease course. The present study employed a principal component analysis (PCA) on multiple clinical variables to investigate effects of cumulative lifetime illness burden on brain structure in a large and heterogeneous sample of MDD patients. Gray matter volumes (GMV) was estimated in n = 681 MDD patients (mean age: 35.87 years; SD = 12.89; 66.6% female) using voxel-based-morphometry. Five clinical variables were included in a PCA to obtain components reflecting disease course to associate resulting components with GMVs. The PCA yielded two main components: Hospitalization reflected by patients' frequency and duration of inpatient treatment and Duration of Illness reflected by the frequency and duration of depressive episodes. Hospitalization revealed negative associations with bilateral dorsolateral prefrontal cortex (DLPFC) and left insula volumes. Duration of Illness showed significant negative associations with left hippocampus and right DLPFC volumes. Results in the DLPFC and hippocampus remained significant after additional control for depressive symptom severity, psychopharmacotherapy, psychiatric comorbidities, and remission status. This study shows that a more severe and chronic lifetime disease course in MDD is associated with reduced volume in brain regions relevant for executive and cognitive functions and emotion regulation in a large sample of patients representing the broad heterogeneity of MDD disease course. These findings were only partly influenced by other clinical characteristics (e.g., remission status, psychopharmacological treatment).

DRD2 Taq1A Polymorphism-Related Brain Volume Changes in Parkinson's Disease: Voxel-Based Morphometry.

Taq1A polymorphism is a DRD2 gene variant located in an exon of the ANKK1 gene and has an important role in the brain's dopaminergic functions. Some studies have indicated that A1 carriers have an increased risk of developing Parkinson's disease (PD) and show poorer clinical performance than A2 homo carriers. Previous studies have suggested that A1 carriers had fewer dopamine D2 receptors in the caudate and increased cortical activity as a compensatory mechanism. However, there is little information about morphological changes associated with this polymorphism in patients with PD. The study's aim was to investigate the relationship between brain volume and Taq1A polymorphism in PD using voxel-based morphometry (VBM). Based on Taq1A polymorphism, 103 patients with PD were divided into two groups: A1 carriers (A1/A1 and A1/A2) and A2 homo carriers (A2/A2). The volume of the left prefrontal cortex (PFC) was significantly decreased in A2 homo carriers compared to A1 carriers. This finding supports the association between Taq1A polymorphism and brain volume in PD and may explain the compensation of cortical function in A1 carriers with PD.

Circulating Lipocalin-2 level is positively associated with cognitive impairment in patients with metabolic syndrome

The association between Lipocalin-2 (LCN2) and cognition in patients with metabolic syndrome (MetS) has not been thoroughly investigated. We aimed to evaluate whether serum LCN2 levels are associated with the alteration of cognitive function in patients with MetS. The total of 191 non-demented participants with MetS were enrolled onto the study in 2015, and a cohort study was conducted in a subpopulation in 2020. After adjustment for sex, age, waist circumference, creatinine levels, and HbA1C, an association between the higher serum LCN2 levels and the lower Montreal cognitive assessment (MoCA) scores was observed (B = − 0.045; 95%CI − 0.087, − 0.004; p 0.030). A total of 30 participants were followed-up in 2020. Serum LCN2 levels were decreased in correlation with age (23.31 ± 12.32 ng/ml in 2015 and 15.98 ± 11.28 ng/ml in 2020, p 0.024), while other metabolic parameters were unchanged. Magnetic resonance imaging studies were conducted on a subsample of patients in 2020 (n = 15). Associations between high serum LCN2 levels from 2015 and 2020 and changes in brain volume of hippocampus and prefrontal cortex from 2020 have been observed. These findings suggest a relationship between changes of the level of circulating LCN2, cognitive impairment, and changes in brain volume in patients with MetS. However, further investigation is still needed to explore the direct effect of circulating LCN2 on the cognition of MetS patients.

Alcohol Use and Prefrontal Cortex Volume Trajectories in Young Adults with Mood Disorders and Associated Clinical Outcomes.

(1) Background: Alcohol use in the course of mood disorders is associated with worse clinical outcomes. The mechanisms by which alcohol use alters the course of illness are unclear but may relate to prefrontal cortical (PFC) sensitivity to alcohol. We investigated associations between alcohol use and PFC structural trajectories in young adults with a mood disorder compared to typically developing peers. (2) Methods: 41 young adults (24 with a mood disorder, agemean = 21 ± 2 years) completed clinical evaluations, assessment of alcohol use, and two structural MRI scans approximately one year apart. Freesurfer was used to segment PFC regions of interest (ROIs) (anterior cingulate, orbitofrontal cortex, and frontal pole). Effects of group, alcohol use, time, and interactions among these variables on PFC ROIs at baseline and follow-up were modeled. Associations were examined between alcohol use and longitudinal changes in PFC ROIs with prospective mood. (3) Results: Greater alcohol use was prospectively associated with decreased frontal pole volume in participants with a mood disorder, but not typically developing comparison participants (time-by-group-by-alcohol interaction; p = 0.007); however, this interaction became a statistical trend in a sensitivity analysis excluding one outlier in terms of alcohol use. Greater alcohol use and a decrease in frontal pole volume related to longer duration of major depression during follow-up (p’s < 0.05). (4) Conclusion: Preliminary findings support more research on alcohol use, PFC trajectories, and depression recurrence in young adults with a mood disorder including individuals with heavier drinking patterns.

Ambient air pollution exposure and increasing depressive symptoms in older women: The mediating role of the prefrontal cortex and insula

Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing depressive symptoms. We evaluated whether smaller volumes of brain structures implicated in late-life depression mediate associations between ambient air pollution exposure and changes in depressive symptoms. This prospective study included 764 community-dwelling older women (aged 81.6 ± 3.6 in 2008–2010) from the Women's Health Initiative Memory Study (WHIMS) Magnetic Resonance Imaging study (WHIMS-MRI; 2005–06) and WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO; 2008–16). Three-year average annual mean concentrations (scaled by interquartile range [IQR]) of ambient PM2.5 (in μg/m3; IQR = 3.14 μg/m3) and NO2 (in ppb; IQR = 7.80 ppb) before WHIMS-MRI were estimated at participants' addresses via spatiotemporal models. Mediators included structural brain MRI-derived grey matter volumes of the prefrontal cortex and structures of the limbic-cortical-striatal-pallidal-thalamic circuit. Depressive symptoms were assessed annually by the 15-item Geriatric Depression Scale. Structural equation models were constructed to estimate associations between exposure, structural brain volumes, and depressive symptoms. Increased exposures (by each IQR) were associated with greater annual increases in depressive symptoms (βPM2.5 = 0.022; 95% Confidence Interval (CI) = 0.003, 0.042; βNO2 = 0.019; 95% CI = 0.001, 0.037). The smaller volume of prefrontal cortex associated with exposures partially mediated the associations of increased depressive symptoms with NO2 (8%) and PM2.5 (13%), and smaller insula volume associated with NO2 contributed modestly (13%) to the subsequent increase in depressive symptoms. We demonstrate the first evidence that the smaller volumes of the prefrontal cortex and insula may mediate the subsequent increases in depressive symptoms associated with late-life exposures to NO2 and PM2.5.

The structural neural correlates of atypical facial expression recognition in autism spectrum disorder.

Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) are worse at recognizing facial expressions than are typically developing (TD) individuals. The present study investigated the differences in structural neural correlates of emotion recognition between individuals with and without ASD using voxel-based morphometry (VBM). We acquired structural MRI data from 27 high-functioning adults with ASD and 27 age- and sex-matched TD individuals. The ability to recognize facial expressions was measured using a label-matching paradigm featuring six basic emotions (anger, disgust, fear, happiness, sadness, and surprise). The behavioural task did not find deficits of emotion recognition in ASD after controlling for intellectual ability. However, the VBM analysis for the region of interest showed a positive correlation between the averaged percent accuracy across six basic emotions and the grey matter volume of the right inferior frontal gyrus in TD individuals, but not in individuals with ASD. The VBM for the whole brain region under each emotion condition revealed a positive correlation between the percent accuracy for disgusted faces and thegrey matter volume of the left dorsomedial prefrontal cortex in individuals with ASD, but not in TD individuals. The different pattern of correlations suggests that individuals with and without ASD use different processing mechanisms for recognizing others' facial expressions.

Neural basis underlying the association between expressive suppression and procrastination: The mediation role of the dorsolateral prefrontal cortex

Procrastination can lead to a variety of negative consequences, including poorer health conditions and more financial issues. Previous researches highlight that procrastination is a result of the failure of emotion-regulation. Although substantial studies have shown that emotion regulation plays an essential role in procrastination, little is known about the neural basis of the relationship between expressive suppression and procrastination. To address this question, we employed the voxel-based morphometry (VBM) method to investigate the neural basis underlying how expressive suppression links to procrastination across two independent samples (sample1, N = 98). Expressive suppression was significantly negatively associated with procrastination. Furthermore, VBM results indicated that expressive suppression was positively correlated with gray matter (GM) volumes of the right dorsolateral prefrontal cortex (dlPFC). More importantly, the GM volumes in dlPFC mediated the relationship between expressive suppression and procrastination, which was further replicated in an independent sample (sample 2, N = 110). These findings suggest that dlPFC, which plays a crucial role in inhibitory control, may be the key brain region mediating the relation between expressive suppression and procrastination. The current work provides a new perspective to understand how emotion regulation in terms of expressive suppression plays a role in procrastination.

Oxytocin attenuates schizophrenia-like reduced sensorimotor gating in outbred and inbred rats in line with strain differences in CD38 gene expression

Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating that is impaired in many clinical conditions, including schizophrenia. The inbred Roman high-avoidance (RHA) rats, compared to their low-avoidance (RLA) counterparts, show distinct schizophrenia-like phenotypes, such as spontaneous deficits in PPI accompanied by decreased medial prefrontal cortex (mPFC) activity and volume. Schizophrenia-like deficits are usually attenuated by antipsychotic drugs, but these drugs often produce severe side effects. In order to reduce these side effects, the neuropeptide oxytocin has been proposed as an alternative natural antipsychotic for schizophrenia. Here, we examined the effects of peripheral oxytocin administration (saline, 0.04, and 0.2 mg/kg) on PPI in the RHA vs. RLA rats, as well as in the outbred heterogeneous stock (HS) rats. Our results showed that oxytocin increased PPI in the HS rats and attenuated PPI deficits in the RHA rats, but it did not significantly affect PPI in the RLAs. To explore whether these divergent effects were associated with differences in oxytocinergic mechanisms, we analyzed gene expression of the oxytocin receptor (OXTR) and the regulator of oxytocin release (CD38) in the mPFC of the Roman rats. Consistent with the differential oxytocin effects on PPI (RHA > RLA), constitutive CD38 expression was reduced in the RHA rats compared to the RLAs, while oxytocin administration increased OXTR expression in both strains. Overall, the present work reveals that oxytocin administration shows antipsychotic-like effects on PPI in outbred and inbred rats, and it suggests that these effects may be related to basal differences in oxytocin-mediated mechanisms in the mPFC.

Structural brain abnormalities associated with cognitive impairments in bipolar disorder.

Cognitive impairment has been highlighted as a core feature of bipolar disorder (BD) that often persists during remission. The specific brain correlates of cognitive impairment in BD remain unclear which impedes efficient therapeutic approaches. In a large sample of remitted BD patients, we investigated whether morphological brain abnormalities within dorsal prefrontal cortex (PFC) and hippocampus were related to cognitive deficits. Remitted BD patients (n=153) and healthy controls (n=52) underwent neuropsychological assessment and structural MRI. Based on hierarchical cluster analysis of neuropsychological test performance, patients were classified as either cognitively impaired (n=91) or cognitively normal (n=62). The neurocognitive subgroups were compared amongst each other and with healthy controls in terms of dorsal PFC cortical thickness and volume, hippocampus shape and volume, and total cerebral grey and white matter volumes. Cognitively impaired patients displayed greater left dorsomedial prefrontal thickness compared to cognitively normal patients and healthy controls. Hippocampal grey matter volume and shape were similar across patient subgroups and healthy controls. At a whole-brain level, cognitively impaired patients had lower cerebral white matter volume compared to the other groups. Across all participants, lower white matter volume correlated with more impaired neuropsychological test performance. Our findings associate cognitive impairment in bipolar disorder with cerebral white matter deficits, factors which may relate to the observed morphological changes in dorsomedial PFC possibly due to increased neurocognitive effort to maintain symptom stability in these remitted patients.

Concurrent Transcranial Direct Current Stimulation and Resting-State Functional Magnetic Resonance Imaging in Patients with Gambling Disorder.

Background/Introduction: Transcranial direct current stimulation (tDCS) delivered over the dorsolateral prefrontal cortex (DLPFC) while patients are at rest can decrease craving in patients with substance-related and addictive disorders. Yet, the effects of tDCS on resting-state brain activity remain unknown in this population. This study examined the effects of tDCS on resting-state functional connectivity (rsFC) with concurrent stimulation and functional magnetic resonance imaging in patients with gambling disorder. Methods: This was a randomized, sham-controlled, double-blind, crossover study. The anodal and cathodal electrodes were applied over the right and left DLPFC, respectively. Patients received 30 min of active and sham stimulation on separate days. rsFC was assessed before and during stimulation with seed-based analyses. Results: There was a significant increase of rsFC between the right DLPFC seed and the right superior parietal lobule during active stimulation as compared to during sham stimulation (p = 0.0059, corrected for multiple comparisons). There was also a positive correlation between rsFC change of this frontoparietal network and brain volume of the right DLPFC (p = 0.0042, corrected for multiple comparisons). Discussion: A single session of tDCS targeting the DLPFC strengthened functional connectivity in a frontoparietal circuit, known to be implicated in cognitive control, especially in patients with a greater volume of the region under the anode electrode. Impact statement Transcranial direct current stimulation increased the functional connectivity of a frontoparietal circuit in patients with gambling disorder. These changes were larger in patients with greater volume of the dorsolateral prefrontal cortex. Transcranial direct current stimulation strengthened the connectivity of a brain network known to be associated with cognitive control.

Higher body mass index associated with smaller frontal cortical volumes in older adult patients with bipolar disorder

Background and objectivesPatients with bipolar disorder (BD) tend to have accelerated decline in executive function during the aging. Thus far, only few studies have examined the effect of obesity on frontal cortical volumes in young patients with BD. Herein we aimed to ascertain the association between body mass index (BMI) and frontal cortical volumes in older adult patients with BD. MethodsWe recruited outpatients who were diagnosed as bipolar I disorder (BD-I) and aged over 50 years to undergo volumetric magnetic resonance imaging and anthropometric measurement. Clinical data were obtained through interview and chart review. ResultsA total of 42 patients (mean age, 59.5±7.9 years) with BD-I were recruited in this study. Compared with normal BMI group, overweight/obese patients (59.5%, n=25) had significantly smaller volumes of the bilateral prefrontal cortex and right orbitofrontal cortex. After adjusting cardiometabolic variables, higher BMI and age were significantly associated with smaller volumes of the left prefrontal cortex and bilateral orbitofrontal cortex, accounting for 29.8% (left prefrontal cortex), 33.1% (left orbitofrontal cortex), and 42.0% (right orbitofrontal cortex) of the variance. BMI alone was negatively associated with the volumes of the right prefrontal and right medial frontal cortexes, accounting for 25.7% and 14.7% of the variance, respectively. ConclusionsHigher BMI was associated with smaller cortical volumes across individual frontal regions in older patients with BD independent of cardiometabolic morbidity. Future research is necessary to elucidate the mechanisms underlying the association between BMI and frontal cortical volumes in older patients with BD.

Prescribing exercise as a treatment for depression

IntroductionDepression is a heterogeneous syndrome linked to significant structural brain abnormalities, such as volumetric reductions in the hippocampus, anterior cingulate cortex and prefrontal cortex, as well as compromised white matter integrity. Recent growing evidence suggests that exercise is a promising and compelling treatment for depression in adults, showing effects that are comparable to other first-line treatments for depression.ObjectivesThis review aims to improve our understanding of the biological pathways involved in both the pathophysiology of depression and the antidepressant effects of exercise.MethodsThis literature review considers the latest available scientific research addressing a comprehensive analysis of the antidepressant effect of physical exercise and the biological pathways involved.ResultsPhysical activity has been shown to have a multimodal effect that stimulates biochemical pathways and restores neuronal structures disturbed in depression. Experimental evidence supports exercise-induced increases in hippocampal, anterior cingulate cortex and prefrontal cortex volume, suggesting that exercise and antidepressant medication may alleviate depression through common neuromolecular mechanisms. However, the benefits of exercise may also persist beyond the end of treatment, unlike antidepressant medication.ConclusionsGiven the undeniable scientific evidence favoring physical exercise in alleviating depression, it is of crucial importance to recommend this treatment in adjunct to psychotherapy and medication. Individuals at risk for depression also greatly benefit from it’s neuroprotective effects and should prioritize lifestyle changes. In older adults, there is a greater need for non-pharmaceutical treatments for depression due to limited efficacy of pharmaceutical treatments in this population.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men.

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators.Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50–70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)].Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits.Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.

Neural basis responsible for self-control association with procrastination: Right MFC and bilateral OFC functional connectivity with left dlPFC

Converging theory and evidence highlights procrastination as a form of self-control failure. However, the underlying neural correlates of how self-control is associated with procrastination remains unclear. As such we investigated the neural basis for self-control association with procrastination using voxel-based morphometry (VBM) and resting-state functional connectivity (FC) approaches. The VBM results showed a positive correlation between self-control and the gray matter volume of left dorsolateral prefrontal cortex (dlPFC). Then the FC of left dlPFC to lateral orbital frontal cortex (lOFC) and right dorsal medial frontal cortex (dMFC) were all negatively correlated to procrastination and showed a mediating effect. This indicates that brain functional communication involves in emotion regulation and valuation processing may account for the association between self-control and procrastination.

Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations.

Preservation of white matter integrity on DTI 3 years after early menopausal hormone therapies

AbstractBackgroundThe critical‐period theory of menopausal hormone therapy (mHT) suggests that if menopausal hormone therapy begins shortly after menopause, it may have beneficial effects on brain structure and cognitive health. We investigated white matter integrity with diffusion tensor MRI (DTI) 3 years after the end of mHT trial in recently menopausal women who were randomized shortly after menopause.MethodParticipants of this study were enrolled in the Kronos Early Estrogen Prevention Study (aged 42–56 years; 5–36 months past menopause). Participants received the following treatments: 0.45 mg/d oral conjugated equine estrogen (oCEE, n=19); 50 μg/d transdermal 17β‐estradiol (tE2, n=22); or placebo (n=33) for 4 years. Oral progesterone (200 mg/d) was given to hormone therapy groups for 12 days each month. DTI was performed 3 years after the end of 4 years of hormone therapy (n=75), which corresponded to 7 years after randomization. Voxel‐based analysis was performed on DTI to evaluate fractional anisotropy (FA) and mean diffusivity (MD) differences between treatment groups (uncorrected p&lt;0.001).ResultVoxel based analysis showed higher FA, a measure of white matter integrity, in the superior corona radiata, anterior limb of the internal capsule and splenium of the corpus callosum of participants treated with oCEE compared to placebo (p &lt;0.001, Figure 1A). Furthermore, higher FA was observed in the superior corona radiata, anterior limb of internal capsule and thalamus in participants treated with tE2 compared to placebo (p &lt;0.001, Figure 1B). There were no differences in FA findings between oCEE and tE2 groups, and no MD differences between treatments groups.ConclusionA relatively higher FA in a variety of white matter regions in the oCEE and tE2 groups compared to placebo suggest that mHT may have long‐term protective effects on white matter integrity. Previously, we had shown that women in the tE2 group preserved their dorsolateral prefrontal cortex volumes better than the placebo group over 7 years. Our findings suggest that the tracts that connect the dorsolateral prefrontal cortex and the thalamus such as the superior corona radiata and the anterior limb of internal capsule may particularly benefit from mHT.

Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation.

Anhedonic symptoms of posttraumatic stress disorder (PTSD) reflect deficits in reward processing that have significant functional consequences. Although recent evidence suggests that disrupted integrity of fronto-limbic circuitry is related to PTSD development, including anhedonic PTSD symptoms (posttrauma anhedonia [PTA]), little is known about potential structural biomarkers of long-term PTA as well as structural changes in fronto-limbic pathways associated with recovery from PTA over time. We investigated associations between white matter microstructure, gray matter volume, and PTA in 75 recently traumatized individuals, with a subset of participants (n = 35) completing follow-up assessment 12 months after trauma exposure. Deterministic tractography and voxel-based morphometry were used to assess changes in white and gray matter structure associated with changes in PTA. Reduced fractional anisotropy (FA) of the uncinate fasciculus at around the time of trauma predicted greater PTA at 12-months posttrauma. Further, increased FA of the fornix over time was associated with lower PTA between 1 and 12-months posttrauma. Increased gray matter volume of the ventromedial prefrontal cortex and precuneus over time was also associated with reduced PTA. The microstructure of the uncinate fasciculus, an amygdala-prefrontal white matter connection, may represent a biomarker of vulnerability for later PTA. Conversely, development and recovery from PTA appear to be facilitated by white and gray matter structural changes in a major hippocampal pathway, the fornix. The present findings shed new light on neuroanatomical substrates of recovery from PTA and characterize white matter biomarkers of risk for posttraumatic dysfunction.

Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Gray matter alteration in heroin-dependent men: An atlas-based magnetic resonance imaging study

Previous imaging studies on heroin addiction have reported brain morphological alterations. However, the effects of heroin exposure on gray matter volume varied among different studies due to different factors such as substitution treatment or mandatory abstinence. Meanwhile, the relationship between gray matter and heroin use history remains unknown. Thirty-three male heroin-dependent (HD) individuals who are not under any substitution treatment or mandatory abstinence and 40 male healthy controls (HC) were included in this structural magnetic resonance imaging study. With an atlas-based approach, gray matter structures up to individual functional area were delineated, and the differences in their volumes between the HD and HC groups were analyzed. In addition, the relationship between gray matter volume and duration of heroin use was explored. The HD group demonstrated significantly lower cortical volume mainly in the prefrontal cortex and mesolimbic dopaminergic regions across different parcellation levels, whereas several visual and somatosensory cortical regions in the HD group had greater volume relative to the HC group at a more detailed parcellation level. The duration of heroin use was negatively correlated with the gray matter volume of prefrontal cortex. These findings suggest that heroin addiction be related to gray matter alteration and might be related to damage/maladaption of the inhibitory control, reward, visual, and somatosensory functions of the brain, although cognitive correlates are warranted in future study. In addition, the atlas-based morphology analysis is a potential tool to help researchers search biomarkers of heroin addiction.