Distinct subcortical neuroanatomic profiles of treatment-resistant schizophrenia: structural magnetic resonance imaging study

Differentiating between bipolar and unipolar depression in functional and structural MRI studies

Several studies have recently demonstrated that the volumes of specific brain regions are reduced in children and adolescents with post-traumatic stress disorder (PTSD) compared with those of healthy controls. Our study investigated the potential association between early traumatic experiences and altered brain regions and functions. We conducted a systematic review of the scientific literature regarding functional magnetic resonance imaging and a meta-analysis of structural magnetic resonance imaging studies that investigated cerebral region volumes in pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial volumes that fit the inclusion criteria were extracted and combined in a meta-analysis that assessed differences between groups. The meta-analysis found reduced total corpus callosum areas and reduced total cerebral and intracranial volumes in the patients with PTSD. The total hippocampus (left and right hippocampus) and gray matter volumes of the amygdala and frontal lobe were also reduced, but these differences were not significant. The functional studies revealed differences in brain region activation in response to stimuli in the post-traumatic stress symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD exhibited structural and functional brain abnormalities and that some of the abnormalities occurred in different brain regions than those observed in adults.

Multimodal neuroimaging features provide opportunities for accurate classification and personalized treatment options in the psychiatric domain. This study aimed to investigate whether brain features predict responses to the overall treatment of schizophrenia at the end of the first or a single hospitalization. Structural and functional magnetic resonance imaging (MRI) data from two independent samples (N=85 and 63, separately) of schizophrenia patients at baseline were included. After treatment, patients were classified as responders and non-responders. Radiomics features of gray matter morphology and functional connectivity were extracted using Least Absolute Shrinkage and Selection Operator. Support vector machine was used to explore the predictive performance. Prediction models were based on structural features (cortical thickness, surface area, gray matter regional volume, mean curvature, metric distortion, and sulcal depth), functional features (functional connectivity), and combined features. There were 12 features after dimensionality reduction. The structural features involved the right precuneus, cuneus, and inferior parietal lobule. The functional features predominately included inter-hemispheric connectivity. We observed a prediction accuracy of 80.38% (sensitivity: 87.28%; specificity 82.47%) for the model using functional features, and 69.68% (sensitivity: 83.96%; specificity: 72.41%) for the one using structural features. Our model combining both structural and functional features achieved a higher accuracy of 85.03%, with 92.04% responder and 80.23% non-responders to the overall treatment to be correctly predicted. These results highlight the power of structural and functional MRI-derived radiomics features to predict early response to treatment in schizophrenia. Prediction models of the very early treatment response in schizophrenia could augment effective therapeutic strategies.

Grief and bereavement: A pre-registered systematic review of neuroimaging studies.

Many eye diseases reduce visual acuity or are associated with visual field defects. Because of the well-defined retinotopic organization of the connections of the visual pathways, this may affect specific parts of the visual pathways and cortex, as a result of either deprivation or transsynaptic degeneration. For this reason, over the past several years, numerous structural magnetic resonance imaging (MRI) studies have examined the association of eye diseases with pathway and brain changes. Here, we review structural MRI studies performed in human patients with the eye diseases albinism, amblyopia, hereditary retinal dystrophies, age-related macular degeneration (AMD) and glaucoma. We focus on two main questions. First, what have these studies revealed? Second, what is the potential clinical relevance of their findings? We find that all the aforementioned eye diseases are indeed associated with structural changes in the visual pathways and brain. As such changes have been described in very different eye diseases, in our view the most parsimonious explanation is that these are caused by the loss of visual input and the subsequent deprivation of the visual pathways and brain regions, rather than by transsynaptic degeneration. Moreover, and of clinical relevance, for some of the diseases - in particular glaucoma and AMD - present results are compatible with the view that the eye disease is part of a more general neurological or neurodegenerative disorder that also affects the brain. Finally, establishing structural changes of the visual pathways has been relevant in the context of new therapeutic strategies to restore retinal function: it implies that restoring retinal function may not suffice to also effectively restore vision. Future structural MRI studies can contribute to (i) further establish relationships between ocular and neurological neurodegenerative disorders, (ii) investigate whether brain degeneration in eye diseases is reversible, (iii) evaluate the use of neuroprotective medication in ocular disease, (iv) determine optimal timing for retinal implant insertion and (v) establish structural MRI examination as a diagnostic tool in ophthalmology.

Memory performance is severely impaired in individuals with schizophrenia. Although several studies have reported a relationship between memory performance and hippocampal volume, only a few structural magnetic resonance imaging (MRI) studies have investigated the relationship between memory performance and subcortical structures other than hippocampus in patients with schizophrenia. We investigated the relationship between memory performance and subcortical regional volumes in a large sample of patients with schizophrenia. Participants included 174 patients with schizophrenia and 638 healthy comparison subjects (HCS). The Wechsler Memory Scale-Revised (WMS-R) has three memory indices (verbal immediate recall, visual immediate recall, and delayed recall (verbal plus visual)) and one control neurocognitive index (attention/concentration). We obtained T1-weighted MRI data and measured the bilateral volumes of the hippocampus, amygdala, thalamus, nucleus accumbens (NA), caudate, putamen, and globus pallidus. Patients with schizophrenia had significantly lower scores for all of the indices of the WMS-R than the HCS. They had more severe impairments in verbal immediate recall and delayed recall than in visual immediate recall and attention/concentration. Verbal immediate recall/delayed recall scores in patients with schizophrenia were significantly correlated not only with hippocampal volume (left: r = 0.34; right: r = 0.28/left: r = 0.33; right: r = 0.31), but also with NA volume (left: r = 0.24; right: r = 0.25/left: r = 0.26; right: r = 0.27). The present investigation with a large sample size did not only replicate hippocampal volume and memory association, but also found that NA volume is associated with memory performances in schizophrenia.

Objective Converging evidence from structural and functional magnetic resonance imaging (MRI) studies points to amygdala alteration as crucial in the development of paediatric bipolar disorder (pBP). The high number of recent studies prompted us to comprehensively evaluate findings. We aimed to systematically review structural and functional MRI studies investigating the amygdala in patients with pBP and in youth at high-risk (HR) for developing pBP. Methods We searched PubMed from any time to 25 September 2020 using: ‘amygdala AND (MRI OR magnetic resonance imaging) AND bipolar AND (pediatr* OR child OR children OR childhood OR adolescent OR adolescents OR adolescence OR young OR familial OR at-risk OR sibling* OR offspring OR high risk)’. In this review, we adhered to the PRISMA statement. Results Amygdala hyperactivity to emotional stimuli is the most commonly reported finding in youth with pBP and HR compared to healthy peers (HC), whereas findings from structural MRI studies are inconsistent. Conclusions Hyperactivation of the amygdala might be an endophenotype of pBP.

BackgroundNeuromelanin (NM), a byproduct of monoamine metabolism, reflects dopamine and norepinephrine activity in the brain. NM-sensitive MRI sequences enable in vivo quantification of NM levels in the substantia nigra (SN) and locus coeruleus (LC), which correspond to dopamine and norepinephrine neuron activity, respectively. Striatal dopamine dysfunction is a hallmark of schizophrenia: increased striatal dopamine synthesis has been associated with responsiveness to first-line antipsychotics (first-line responders [FLR]), whereas normal striatal dopamine synthesis characterizes treatment-resistant schizophrenia (TRS). Clozapine is the only approved treatment for TRS; however, its relationship with NM-MRI-derived dopamine markers remains unexplored. Additionally, norepinephrine dysregulation, originating in the LC, has been implicated in delusions and cognitive impairments in schizophrenia, yet its role in treatment response remains unvalidated using NM-MRI.Aims & ObjectivesThis study aims to elucidate the relationship between NM accumulation and treatment responsiveness in schizophrenia. Specifically, we sought to:Compare NM-MRI-derived signal intensities in the SN and LC among schizophrenia subgroups and healthy controls (HCs).Investigate differences in NM-related dopaminergic and noradrenergic activity between clozapine-nonresponsive TRS (ultra-resistant schizophrenia [URS]) and clozapine-responsive TRS (non-URS).Explore associations between NM-MRI findings and clinical characteristics, including symptom severity and treatment outcomes.MethodWe conducted a cross-sectional study involving four groups: URS (n = 16), non-URS (n = 16), FLR (n = 20), and HCs (n = 26). NM-MRI was used to measure NM signals in the SN and LC, quantified as contrast ratios (CR). Group comparisons were performed, controlling for age and sex, with Benjamini–Hochberg correction applied for multiple comparisons. Associations between CR and clinical characteristics were also analyzed.ResultsOf the 78 participants, two (1 URS, 1 FLR) were excluded due to insufficient data quality. Significant group differences were observed in CR for both the SN and LC (SN: F(3,70) = 4.45, η² = 0.16, p = 0.01; LC: F(3,70) = 2.87, η² = 0.11, p = 0.04). In the SN, both URS (Cohen’s d = 1.01, p = 0.01) and FLR (Cohen’s d = 0.94, p = 0.01) showed elevated CR compared to HCs. In the LC, URS demonstrated higher CR than FLR (Cohen’s d = 0.99, p = 0.04). No significant associations were found between CR and clinical characteristics or symptom severity.Discussion & ConclusionsThis study highlighted distinct dopaminergic and noradrenergic activity patterns in schizophrenia subgroups. Elevated dopaminergic activity (SN CR) was observed in both URS and FLR, whereas heightened noradrenergic activity (LC CR) differentiated URS from FLR. These findings suggest NM-MRI’s potential in predicting treatment response in schizophrenia, underscoring the need for longitudinal studies to establish its clinical utility.

Hippocampal and Amygdalar Volumes in Breast Cancer Survivors with Posttraumatic Stress Disorder

Although smaller hippocampi and amygdalae were found in cancer survivors with intrusions, associations between cancer-related posttraumatic stress disorder (PTSD) and these volumes are unknown. The authors performed MRI volumetric analyses of these regions in 15 cancer survivors with PTSD, 15 cancer survivors without PTSD, and 15 healthy comparison subjects. The authors also examined the correlation between PTSD symptom scores of the Impact of Event Scale and these volumes in the PTSD group. These volumes were not significantly different among the groups, but the intrusion score was inversely associated with the hippocampal volume. Results suggest intrusions, not PTSD diagnosis, might be associated with hippocampal volume.

Investigating the relationship between premorbid functioning and treatment response in schizophrenia is relevant to understanding the illness and predicting treatment outcomes. To examine the relationship between premorbid characteristics and treatment response of people with recent-onset schizophrenia. Data came from a large, double-blind trial of recent-onset psychosis treated with a flexible dose of risperidone or haloperidol. Median treatment length was 206 days. Premorbid functioning was categorised using the Cannon-Spoor Premorbid Adjustment Scale. There were significant differences between the premorbid groups on change on the Positive and Negative Syndrome Scale, Clinical Global Impression severity and cognitive functioning and Extrapyramidal Symptoms Rating Scale. Patients in the ;stable-good' premorbid group (n = 251) improved more than those in the'stable-poor' (n = 198) and 'declining' (n = 81) groups. The ;stable-good' group received the lowest doses of antipsychotic and had the least extrapyramidal symptoms. Patients in the 'declining' group had the highest dosages and the most extrapyramidal symptoms. In first-episode psychosis good premorbid functioning is associated with better response to treatment and fewer extrapyramidal symptoms.

Correlation between amygdala volume and age in bipolar disorder — A systematic review and meta-analysis of structural MRI studies

Adverse childhood experiences and left hippocampal volumetric reductions: A structural magnetic resonance imaging study

This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamate-mediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depression-related neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

Multisite schizophrenia classification by integrating structural magnetic resonance imaging data with polygenic risk score