Objective:
Schizophrenia is a devastating mental disorder accompanied by aberrant structural brain connectivity. The question whether schizophrenia is a progressive brain disorder is yet to be ...resolved. Thus, it is not clear when these structural alterations occur and how they develop over time.
Methods:
In our selective review, we summarized recent findings from longitudinal magnetic resonance imaging studies investigating structural brain alterations and its impact on clinical outcome at different stages of the illness: (1) subjects at ultra-high risk of developing psychosis, (2) patients with a first episode psychosis, and (3) chronically ill patients. Moreover, we reviewed studies examining the longitudinal effects of medication on brain structure in patients with schizophrenia.
Results:
(1) Studies from pre-clinical stages to conversion showed a more pronounced cortical gray matter loss (i.e. superior temporal and inferior frontal regions) in those individuals who later made transition to psychosis. (2) Studies investigating patients with a first episode psychosis revealed a decline in multiple gray matter regions (i.e. frontal regions and thalamus) over time as well as progressive cortical thinning in the superior and inferior frontal cortex. (3) Studies focusing on patients with chronic schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal and temporal areas, thalamus, and cingulate cortices)—especially in poor-outcome patients. Very few studies reported effects on white matter microstructure in the longitudinal course of the illness.
Conclusion:
There is adequate evidence to suggest that schizophrenia is associated with progressive gray matter abnormalities particularly during the initial stages of illness. However, causal relationships between structural changes and illness course—especially in chronically ill patients—should be interpreted with caution. Findings might be confounded by longer periods of treatment and higher doses of antipsychotics or epiphenomena related to the illness.
Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing ...NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine ...learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.
Patients suffering from major depressive disorder (MDD) show deficits in working memory (WM) performance accompanied by bilateral fronto-parietal BOLD signal changes. It is unclear whether patients ...with a first depressive episode (FDE) exhibit the same signal changes as patients with recurrent depressive episodes (RDE).
We investigated seventy-four MDD inpatients (48 RDE, 26 FDE) and 74 healthy control (HC) subjects performing an n-back WM task (0-back, 2-back, 3-back condition) in a 3T-fMRI.
FMRI analyses revealed deviating BOLD signal in MDD in the thalamus (0-back vs. 2-back), the angular gyrus (0-back vs. 3-back), and the superior frontal gyrus (2-back vs. 3-back). Further effects were observed between RDE vs. FDE. Thus, RDE displayed differing neural activation in the middle frontal gyrus (2-back vs. 3-back), the inferior frontal gyrus, and the precentral gyrus (0-back vs. 2-back). In addition, both HC and FDE indicated a linear activation trend depending on task complexity.
Although we failed to find behavioral differences between the groups, results suggest differing BOLD signal in fronto-parietal brain regions in MDD vs. HC, and in RDE vs. FDE. Moreover, both HC and FDE show similar trends in activation shapes. This indicates a link between levels of complexity-dependent activation in fronto-parietal brain regions and the stage of MDD. We therefore assume that load-dependent BOLD signal during WM is impaired in MDD, and that it is particularly affected in RDE. We also suspect neurobiological compensatory mechanisms of the reported brain regions in (working) memory functioning.
•WM-load is accompanied by bilateral fronto-parietal signal changes.•MDD patients exhibit altered BOLD signal in regions comprising the SFG, AG, and thalamus.•RDE patients exhibit altered BOLD signal in the MFG, PCG, and IFG as compared to FDE.•Both HC and FDE indicate a linear activation trend depending on task complexity.•We conclude a link between impaired signal changes and the course/stage of depression.
Major depression is associated with impairments in semantic verbal fluency (VF). However, the neural correlates underlying dysfunctional cognitive processing in depressed subjects during the ...production of semantic category members still remain unclear. In the current study, an overt and continuous semantic VF paradigm was used to examine these mechanisms in a representative sample of 33 patients diagnosed with a current episode of unipolar depression and 33 statistically matched healthy controls. Subjects articulated words in response to semantic category cues while brain activity was measured with functional magnetic resonance imaging (fMRI). Compared to controls, patients showed poorer task performance. On the neural level, a group by condition interaction analysis, corrected for task performance, revealed a reduced task-related deactivation in patients in the right parahippocampal gyrus, the right fusiform gyrus, and the right supplementary motor area. An additional and an increased task-related activation in patients were observed in the right precentral gyrus and the left cerebellum, respectively. These results indicate that a failure to suppress potentially interfering activity from inferior temporal regions involved in default-mode network functions and visual imagery, accompanied by an enhanced recruitment of areas implicated in speech initiation and higher-order language processes, may underlie dysfunctional cognitive processing during semantic VF in depression. The finding that patients with depression demonstrated both decreased performance and aberrant brain activation during the current semantic VF task demonstrates that this paradigm is a sensitive tool for assessing brain dysfunctions in clinical populations.
Abstract Genetic studies found the A allele of the single nucleotide polymorphism rs1006737 in the CACNA1C gene, which encodes for the alpha 1C subunit of the voltage-dependent, L-type calcium ion ...channel Cav 1.2, to be overrepresented in patients with major depressive disorder (MDD). Altered prefrontal brain functioning and impaired semantic verbal fluency (SVF) are robust findings in these patients. A recent functional magnetic resonance imaging (fMRI) study found the A allele to be associated with poorer performance and increased left inferior frontal gyrus (IFG) activation during SVF tasks in healthy subjects. In the present study, we investigated the effects of rs1006737 on neural processing during SVF in MDD. In response to semantic category cues, 40 patients with MDD and 40 matched controls overtly generated words while brain activity was measured with fMRI. As revealed by whole brain analyses, genotype significantly affected brain activity in patients. Compared to patients with GG genotype, patients with A allele demonstrated increased task-related activation in the left middle/inferior frontal gyrus and the bilateral cerebellum. Patients with A allele also showed enhanced functional coupling between left middle/inferior and right superior/middle frontal gyri. No differential effects of genotype on SVF performance or brain activation were found between diagnostic groups. The current data provide further evidence for an impact of rs1006737 on the left IFG and demonstrate that genetic variation in CACNA1C modulates neural responses in patients with MDD. The observed functional alterations in prefrontal and cerebellar areas might represent a mechanism by which rs1006737 influences susceptibility to MDD.
Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, ...we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction.
The alpha 1C subunit of the L-type voltage-gated calcium channel (
CACNA1C)
gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is ...involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the
CACNA1C
single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus. These results, however, are inconsistent with regard to the magnitude and directionality of effect. In the present study, brain activation was measured with fMRI during an episodic memory encoding and retrieval task using neutral faces in two independent samples of 94 and 111 healthy subjects, respectively. Within whole brain analyses, a main effect of genotype emerged mainly in the right hippocampus during encoding as well as retrieval within the first sample: Carriers of the minor allele (A) exhibited lower activations compared to G/G allele carriers. This effect could be replicated within the second sample, however, only for the retrieval condition. The results strengthen findings that rs1006737 is associated with neural systems related to memory processes in hippocampal regions which are detectable in healthy subjects.
10Kin1day: A Bottom-Up Neuroimaging Initiative van den Heuvel, Martijn P; Scholtens, Lianne H; van der Burgh, Hannelore K ...
Frontiers in neurology,
05/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a ...3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.
City living represents not only the allegory of modern life, but also – due to attractive living conditions, employment and infrastructure – a crucial reality for a growing portion of the global ...society. Regarding the remarkable increase of the schizophrenia incidence in individuals exposed to an urban environment during upbringing the understanding of responsible pathogenetic mechanisms is important. Schizophrenia has been conceptualized as a disorder of brain dysconnectivity. We investigated the association between urban upbringing and gray matter as well as white matter in a large sample of healthy subjects (n = 290). Voxelwise analyses revealed a strong inverse correlation of early life urbanicity and gray matter volume of the bilateral dorsolateral prefrontal cortices (DLPFC) and the right inferior parietal lobe (IPL) as well as the white matter characteristics in the left superior longitudinal fasciculus (SLF). A positive correlation was found for the gray matter volume of the left precuneus. These results may point to an altered brain development associated with urban upbringing, which not only affects single brain regions but a fronto-parietal network. Considering a DLPFC susceptibility to stress, our findings support the hypothesis of the pathogenetic role of social stress in an urban environment.
PDF
