Putamen Volume Research Articles

Long-standing multiple sclerosis neurodegeneration: volumetric magnetic resonance imaging comparison to Parkinson’s disease, mild cognitive impairment, Alzheimer’s disease, and elderly healthy controls

Multiple sclerosis (MS) exhibits neurodegeneration driven disability progression. We compared the extent of neurodegeneration among 112 long-standing MS patients, 37 Parkinson’s disease (PD) patients, 34 amnestic mild cognitive impairment (aMCI) patients, 37 Alzheimer’s disease (AD) patients, and 184 healthy controls. 3T MRI volumes of whole brain (WBV), white matter (WMV), gray matter (GMV), cortical (CV), deep gray matter (DGM), and nuclei-specific volumes of thalamus, caudate, putamen, globus pallidus, and hippocampus were derived with SIENAX and FIRST software. Аge and sex-adjusted analysis of covariance was used. WBV was not significantly different between diseases. MS had significantly lower WMV compared to other disease groups (p < 0.021). Only AD had smaller GMV and CV when compared to MS (both p < 0.001). MS had smaller DGM volume than PD and aMCI (p < 0.001 and p = 0.026, respectively) and lower thalamic volume when compared to all other neurodegenerative diseases (p < 0.008). Long-standing MS exhibits comparable global atrophy with lower WMV and thalamic volume when compared to other classical neurodegenerative diseases.

Abstract WP494: Neuroimaging Correlates of Apathy in Late-Onset Depression

Apathy is prevalent in older depressed patients and considered to be a predictor of increased dementia risk. Neuroimaging characteristics of late-life depression are being discussed. However, it is unclear whether apathetic (ApD) and nonapathetic depression (D) have different neuroimaging correlates. The objective of this study was to examine structural and functional bases of ApD by using morphometric and functional connectivity MRI analyses. We enrolled 45 consecutive patients with late-onset depression (85% female; mean age=66 (4) years, mean education=14 (2) years) and 22 age and gender-matched healthy elderly. Patients were divided into ApD (n=26) and D (n=19) groups based on Apathy Scale scores. All the participants underwent 1.5 T structural MRI and resting-state fMRI. Fazekas scale was used to quantify white matter hyperintensities. Demographic data, Hamilton Depression Rating Scale (HAMD), Apathy Scale, and MoCA scores for the three groups were compared. Association between apathy, depression and neuroimaging characteristics was assessed using regression analysis with demographic and cognitive variables included as covariates. ApD patients demonstrated nonsignificantly higher HAMD and Fazekas scores and lower MoCA scores compared to D patients. The latter group showed similar Fazekas and slightly lower MoCA scores vs healthy elderly. After controlling for covariates, apathy was significantly associated with volumes of nucleus caudatus and putamen on the right as well as functional connectivity between anterior cingulate and parahippocampal gyrus. Depression correlated with the volumes of the cerebral and cerebellum cortices as well as functional connectivity of salience resting state network. Our study demonstrated an association between volumes of basal ganglia, functional connectivity of anterior cingulate and apathy in late-onset depression.

Volume changes of subcortical structures in patients with post-hepatitis B cirrhosis: A magnetic resonance imaging study.

To investigate volume changes of subcortical structures in patients with post-hepatitis B cirrhosis. Thirty patients with post-hepatitis B cirrhosis (the cirrhosis group) and 24 age- and sex-matched healthy controls (the control group) were enrolled in this prospective study. All subjects underwent neuropsychological tests, blood biochemical determinations, and cerebral MRI. Volumes of 18 selected subcortical structures were automatically segmented and analyzed by the FreeSurfer. In the cirrhosis group, the relationships between abnormal subcortical volumes and clinical index or neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal hyperintensity were also examined. Compared with the healthy controls, patients with post-hepatitis B cirrhosis displayed smaller bilateral putamen, amygdala, and nucleus accumbens volumes and larger bilateral globus pallidus volumes (P<0.001 or P=0.001). In the cirrhosis group, the volumes of left putamen and amygdala were negatively correlated with the number connection test-A (NCT-A)(left putamen r=-0.410, P=0.034; left amygdala r=-0.439, P=0.022), and the volumes of bilateral globus pallidus were positively correlated with pallidal index (PI) (left globus pallidus r=0.889, P<0.001; right globus pallidus r=0.900, P<0.001). Abnormalities of subcortical volumes appear bilaterally symmetrical in patients with post-hepatitis B cirrhosis. Atrophy of left putamen and amygdala might contribute to poor neurocognitive performance, and the manganese deposition might contribute to the increased globus pallidus volumes in patients with post-hepatitis B cirrhosis.

Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD.

Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. Children 7-15 years old were recruited for a case-control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = -0.147 (-0.27 to -0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

TENSOR-BASED GRADING: A NOVEL PATCH-BASED GRADING APPROACH FOR THE ANALYSIS OF DEFORMATION FIELDS IN HUNTINGTON'S DISEASE.

The improvements in magnetic resonance imaging have led to the development of numerous techniques to better detect structural alterations caused by neurodegenerative diseases. Among these, the patch-based grading framework has been proposed to model local patterns of anatomical changes. This approach is attractive because of its low computational cost and its competitive performance. Other studies have proposed to analyze the deformations of brain structures using tensor-based morphometry, which is a highly interpretable approach. In this work, we propose to combine the advantages of these two approaches by extending the patch-based grading framework with a new tensor-based grading method that enables us to model patterns of local deformation using a log-Euclidean metric. We evaluate our new method in a study of the putamen for the classification of patients with pre-manifest Huntington's disease and healthy controls. Our experiments show a substantial increase in classification accuracy (87.5 ± 0.5 vs. 81.3 ± 0.6) compared to the existing patch-based grading methods, and a good complement to putamen volume, which is a primary imaging-based marker for the study of Huntington's disease.

Subcortical gray matter changes in pediatric patients with new-onset juvenile myoclonic epilepsy

ObjectiveThe objective of the study was to identify the relationship between subcortical gray matter (GM) volumes and juvenile myoclonic epilepsy (JME). MethodsWe analyzed the brain magnetic resonance imaging (MRI) scans that were performed during the time of the diagnosis of epilepsy by using voxel-based morphometry (VBM) method. The volumetric three-dimensional sequence was used for structural investigation. The volumes of the thalamus, caudate nucleus, pallidum, and putamen were measured in both hemispheres of patients with JME, patients with generalized tonic–clonic seizures alone (GTCS) (as a disease control group) and healthy controls (HCs). All patients were drug-naïve, and treatment had been started after evaluating MRI results. ResultsFifteen patients with JME (9 females, mean age = 16.1 ± 3.2), 18 patients with GTCS (10 females, mean age = 15.5 ± 2.9), and 43 HCs (24 females, mean age = 15.9 ± 2.8) were included in the analysis. No significant difference was found for relative globus pallidus, caudate, and putamen volumes among the groups with JME, GTCS, and the HC group. The relative left and right thalamic volumes were significantly different between groups (Kruskal–Wallis rank test, p = 0.007, p = 0.001). In pairwise comparisons, both right and left relative thalamic volumes were lower in patients with JME than in HCs (right thalamus: means: 0.521 ± 0.066 vs. 0.597 ± 0.058, p < 0.001; left thalamus: means: 0.526 ± 0.088 vs. 0.605 ± 0.057, p < 0.001, Bonferroni post hoc corrections) and in patients with JME than in patients with GTCS (right thalamus: means: 0.521 ± 0.066 vs. 0.578 ± 0.066, p = 0.03; left thalamus: means: 0.526 ± 0.088 vs. 0.592 ± 0.068, p = 0.01, Bonferroni post hoc corrections), whereas there was no significant difference between the HCs and patients with GTCS (right thalamus: means: 0.597 ± 0.058 vs. 0.578 ± 0.066, p = 0.8; left thalamus: means: 0.605 ± 0.057 vs. 0.592 ± 0.068, p = 0.999, Bonferroni post hoc corrections). ConclusionThis study allowed us to know that microstructural abnormalities exist from the disease onset, and the thalamus might play a critical role in the pathogenesis of JME.

Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.

Brain atrophy and employment in multiple sclerosis patients: a 10-year follow-up study.

BackgroundMultiple sclerosis is often associated with unemployment. The contribution of grey matter atrophy to unemployment is unclear.ObjectivesTo identify magnetic resonance imaging biomarkers of grey matter and clinical symptoms associated with unemployment in multiple sclerosis patients.MethodsDemographic, clinical data and 1.5 T magnetic resonance imaging scans were collected in 81 patients at the time of inclusion and after 5 and 10 years. Global and tissue-specific volumes were calculated at each time point. Statistical analysis was performed using a mixed linear model.ResultsAt baseline 31 (38%) of the patients were unemployed, at 5-year follow-up 44 (59%) and at 10-year follow-up 34 (81%) were unemployed. The unemployed patients had significantly lower subcortical deep grey matter volume (P < 0.001), specifically thalamus, pallidus, putamen and hippocampal volumes, and cortical volume (P = 0.011); and significantly greater T1 (P < 0.001)/T2 (P < 0.001) lesion volume than the employed patient group at baseline. Subcortical deep grey matter volumes, and to a lesser degree cortical volume, were significantly associated with unemployment throughout the follow-up.ConclusionWe found significantly greater atrophy of subcortical deep grey matter and cortical volume at baseline and during follow-up in the unemployed patient group. Atrophy of subcortical deep grey matter showed a stronger association to unemployment than atrophy of cortical volume during the follow-up.

Gray Matter Atrophy in Parkinson's Disease and the Parkinsonian Variant of Multiple System Atrophy: A Combined ROI- and Voxel-Based Morphometric Study

OBJECTIVES:Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM).METHODS:We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM.RESULTS:ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05).CONCLUSIONS:Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.

Mental fatigue in stress-related exhaustion disorder: Structural brain correlates, clinical characteristics and relations with cognitive functioning

Emerging evidence suggests that mental fatigue is a central component of the cognitive and clinical characteristics of stress-related exhaustion disorder (ED). Yet, the underlying mechanisms of mental fatigue in this patient group are poorly understood. The aim of this study was to investigate cortical and subcortical structural neural correlates of mental fatigue in patients with ED, and to explore the association between mental fatigue and cognitive functioning. Fifty-five patients with clinical ED diagnosis underwent magnetic resonance imaging. Mental fatigue was assessed using the Concentration subscale from the Checklist Individual Strength. Patients with high levels of mental fatigue (n = 30) had smaller caudate and putamen volumes compared to patients with low-moderate levels of mental fatigue (n = 25). No statistically significant differences in cortical thickness were observed between the groups. Mediation analysis showed that mental fatigue mediated the relationship between caudate volume and working memory; specifically, smaller caudate volume was associated with higher level of mental fatigue and mental fatigue was positively associated with working memory performance. Our findings demonstrate that the structural integrity of the striatum is of relevance for the subjective perception of mental fatigue in ED, while also highlighting the complex relationship between mental fatigue, cognitive performance and its neural underpinnings.

Neuroanatomical profiles of treatment-resistance in patients with schizophrenia spectrum disorders

Widespread structrual abnormalities in subcortical brain regions have been identified in patients with schizophrenia. However, only a few studies have examined the neuroanatomical profiles of patients with treatment-resistant schizophrenia. The aim of this study was to compare differences in subcortical and hippocampal volumes between: (i) treatment-resistant patients who are non-responders to both first-line antipsychotics and clozapine (URS), (ii) treatment-resistant patients who are non-responders to first-line antipsychotics but are responders to clozapine (CLZ-Resp), (iii) responders to first-line antipsychotics (FL-Resp), and (iv) healthy controls. T1-weighted images of 103 participants (27 URS, 29 CLZ-Resp, 21 FL-Resp, and 26 healthy controls) were obtained. Group differences in striatal, thalamic, globus pallidus, amygdala, and hippocampus volumes were examined. Multiple regression analyses were performed to examine the associations between subcortical and hippocampal volumes and participant characteristics. The FL-Resp group showed larger striatal and globus pallidus volumes compared to the URS group and larger post-commissural putamen and globus pallidus volumes compared to healthy controls. The URS group showed smaller thalamic volume compared to healthy controls. There were no subcortical or hippocampal volume differences between the URS and CLZ-Resp groups. Differences in subcortical and hippocampal structural volumes were not related to symptom severity or chlorpromazine antipsychotic dose equivalents. Our findings suggest different structural volume alterations in subcortical brain regions between treatment-resistant schizophrenia and responders to first-line antipsychotics. Whether subcortical structure compromise is a distinct pathophysiological marker of treatment-resistant schizophrenia, or a result of antipsychotic exposure, remains to be explored.

P.047 Circulating exosomal microRNAs in bipolar disorder

Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that emerges in childhood and persists into adulthood in a sizeable portion of afflicted individuals. The persistence of ADHD symptoms elevates the risk of adverse outcomes that result in substantial individual and societal burden. The objective of this study was to delineate neuroanatomical substrates associated with the diversity of adult outcomes of childhood ADHD, which may have considerable value for development of novel interventions that target mechanisms associated with recovery. Structural MRI and diffusion tensor imaging data from 32 young adults who were diagnosed with ADHD combined-type during childhood and 35 group-matched controls were analyzed. Adults with childhood ADHD were divided into 16 remitters and 16 persisters based on DSM-IV criteria. Compared to the controls, ADHD probands showed significantly reduced gray matter (GM) volume in right putamen and white matter (WM) volume in left parieto-insular fiber tracts. Within the ADHD probands, the remitters, as compared to persisters, showed significantly greater volume of right hippocampo-frontal and right parieto-insular WM fiber tracts, and those connecting caudate with the frontal, parietal, occipital, temporal, and insular cortices. Among ADHD probands, increased fractional anisotropy value of left caudate-parietal tract was significantly correlated with reduced hyperactive/impulsive symptoms. These findings suggest that optimal structural development in the WM tracts that connect caudate with cortical areas, especially in the caudate-parietal path, may play an important role in symptom remission in young adults with childhood ADHD.

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10-7). These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).

The role of genes affected by human evolution marker GNA13 in schizophrenia

Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.

Shared Neural Phenotypes for Mood and Anxiety Disorders

Major depressive disorder, bipolar disorder, posttraumatic stress disorder, and anxiety disorders are highly comorbid and have shared clinical features. It is not yet known whether their clinical overlap is reflected at the neurobiological level. To detect transdiagnostic convergence in abnormalities in task-related brain activation. Task-related functional magnetic resonance imaging articles published in PubMed, Web of Science, and Google Scholar during the last decade comparing control individuals with patients with mood, posttraumatic stress, and anxiety disorders were examined. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines, articles were selected if they reported stereotactic coordinates of whole-brain-based activation differences between adult patients and control individuals. Coordinates of case-control differences coded by diagnosis and by cognitive domain based on the research domain criteria were analyzed using activation likelihood estimation. Identification of transdiagnostic clusters of aberrant activation and quantification of the contribution of diagnosis and cognitive domain to each cluster. A total of 367 experiments (major depressive disorder, 149; bipolar disorder, 103; posttraumatic stress disorder, 55; and anxiety disorders, 60) were included comprising observations from 4507 patients and 4755 control individuals. Three right-sided clusters of hypoactivation were identified centered in the inferior prefrontal cortex/insula (volume, 2120 mm3), the inferior parietal lobule (volume, 1224 mm3), and the putamen (volume, 888 mm3); diagnostic differences were noted only in the putamen (χ23 = 8.66; P = .03), where hypoactivation was more likely in bipolar disorder (percentage contribution = 72.17%). Tasks associated with cognitive systems made the largest contribution to each cluster (percentage contributions >29%). Clusters of hyperactivation could only be detected using a less stringent threshold. These were centered in the perigenual/dorsal anterior cingulate cortex (volume, 2208 mm3), the left amygdala/parahippocampal gyrus (volume, 2008 mm3), and the left thalamus (volume, 1904 mm3). No diagnostic differences were observed (χ23 < 3.06; P > .38), while tasks associated with negative valence systems made the largest contribution to each cluster (percentage contributions >49%). All findings were robust to the moderator effects of age, sex, and magnetic field strength of the scanner and medication. In mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent transdiagnostic abnormalities in task-related brain activity converge in regions that are primarily associated with inhibitory control and salience processing. Targeting these shared neural phenotypes could potentially mitigate the risk of affective morbidity in the general population and improve outcomes in clinical populations.

Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study

Children of parents with depression are two to three times more likely to develop major depressive disorder than children without parental history; however, subcortical brain volume abnormalities characterizing major depressive disorder risk remain unclear. The Adolescent Brain and Cognitive Development (ABCD) Study provides an opportunity to identify subcortical differences associated with parental depressive history. Structural magnetic resonance data were acquired from 9- and 10-year-old children (N= 11,876; release 1.1, n= 4,521; release 2.0.1, n= 7,355). Approximately one-third of the children had a parental depressive history, providing sufficient power to test differences in subcortical brain volume between low- and high-risk youths. Children from release 1.1 were examined as a discovery sample, and we sought to replicate effects in release 2.0.1. Secondary analyses tested group differences in the prevalence of depressive disorders and clarified whether subcortical brain differences were present in youths with a lifetime depressive disorder history. Parental depressive history was related to smaller right putamen volume in the discovery (release 1.1; d=-0.10) and replication (release 2.0.1; d=-0.10) samples. However, in release 1.1, this effect was driven by maternal depressive history (d=-0.14), whereas in release 2.0.1, paternal depressive history showed a stronger relationship with putamen volume (d=-0.09). Furthermore, high-risk children exhibited a near twofold greater occurrence of depressive disorders relative to low-risk youths (maternal history odds ratio=1.99; paternal history odds ratio= 1.45), but youths with a lifetime depressive history did not exhibit significant subcortical abnormalities. A parental depressive history was associated with smaller putamen volume, which may affect reward learning processes that confer increased risk for major depressive disorder.

Inflammation and depressive phenotypes: evidence from medical records from over 12 000 patients and brain morphology.

Preclinical and human studies suggest an association between chronic inflammation and the development of depressive behaviors. This is proposed to occur through downstream effects of inflammatory cytokines on neuroplasticity, neurogenesis and neurotransmitter function, although the neural correlates remain poorly understood in humans. In Study 1, structural magnetic resonance imaging and serum inflammatory cytokine data were analyzed from 53 psychiatrically healthy female participants. Correlational analyses were conducted between interleukin-6 (IL-6) and volume in a priori regions implicated in the pathophysiology of major depressive disorder (MDD). In Study 2, medical data [including serum inflammatory acute phase reactants (C-reactive protein)] were analyzed for 12 589 participants. Participants were classified as having (n = 2541) v. not having (n = 10 048) probable lifetime MDD using phenotypes derived using machine-learning approaches. Non-parametric analyses compared inflammation between groups, whereas regression analyses probed whether inflammation predicted probable MDD classification while accounting for other variables. In Study 1, significant negative correlations emerged between IL-6 and hippocampal, caudate, putamen and amygdalar volume. In Study 2, the MDD group showed a higher probability of elevated inflammation than the non-MDD group. Moreover, elevated inflammation was a significant predictor of probable MDD classification. Findings indicate that inflammation is cross-sectionally related to reduced volume in brain regions implicated in MDD phenotypes among a sample of psychiatrically healthy women, and is associated with the presence of probable MDD in a large clinical dataset. Future investigations may identify specific inflammatory markers predicting first MDD onset.

Effects of Age and Sex on Subcortical Volumes.

PurposeIn an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala.MethodsWe analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set.ResultsThe sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased.ConclusionThe results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.

Quantitative Validation of a Visual Rating Scale for Defining High-Iron Putamen in Patients With Multiple System Atrophy.

Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA).Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2* values and the volume of the entire putamen were measured.Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2* values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2* values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2* values ≥ third quartile, and the remaining patients.Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA.

The association of striatal volume and positive schizotypy in healthy subjects: intelligence as a moderating factor.

Schizotypy, a putative schizophrenia endophenotype, has been associated with brain-structural variations partly overlapping with those in psychotic disorders. Variations in precuneus structure have been repeatedly reported, whereas the involvement of fronto-striatal networks - as in schizophrenia - is less clear. While shared genetic architecture is thought to increase vulnerability to environmental insults, beneficial factors like general intelligence might buffer their effect. To further investigate the role of fronto-striatal networks in schizotypy, we examined the relationship of voxel- and surface-based brain morphometry and a measure of schizotypal traits (Schizotypal Personality Questionnaire, with subscores Cognitive-Perceptual, Interpersonal, Disorganised) in 115 healthy participants [54 female, mean age (s.d.) = 27.57(8.02)]. We tested intelligence (MWT-B) as a potential moderator. We found a positive association of SPQ Cognitive-Perceptual with putamen volume (p = 0.040, FWE peak level-corrected), moderated by intelligence: with increasing IQ, the correlation of SPQ Cognitive-Perceptual and striatal volume decreased (p = 0.022). SPQ Disorganised was positively correlated with precentral volume (p = 0.013, FWE peak level-corrected). In an exploratory analysis (p < 0.001, uncorrected), SPQ total score was positively associated with gyrification in the precuneus and postcentral gyrus, and SPQ Disorganised was negatively associated with gyrification in the inferior frontal gyrus. Our findings support the role of fronto-striatal networks for schizotypal features in healthy individuals, and suggest that these are influenced by buffering factors like intelligence. We conclude that protective factors, like general cognitive capacity, might attenuate the psychosis risk associated with schizotypy. These results endorse the idea of a continuous nature of schizotypy, mirroring similar findings in schizophrenia.