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- Gallo, Selene, et al.
(författare)
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Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:7, s. 3013-3022
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Tidskriftsartikel (refereegranskat)abstract
- The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73-81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.
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| 2. |
- Perini, Irene, 1983-, et al.
(författare)
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Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; :6, s. 2563-2571
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Tidskriftsartikel (refereegranskat)abstract
- Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.
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| 3. |
- Paul, Elisabeth R., 1991-
(författare)
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Immunological Changes and Brain Function over a Psychotic-Depressive Spectrum
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychotic and depressive disorders are severe psychiatric disorders that contribute significantly to the global burden of disease. They are distinct disorders with different symptom profiles according to both the Diagnostic and Statistical Manual and the International Classification of Diseases. However, these disorders share commonalities in various aspects, such as high comorbidity, prevalence of subclinical symptoms, and shared genetics. Furthermore, both disorders have been associated with a dysregulated immune system functioning.In this thesis, we aimed to identify common biological dimensions of both depression and psychosis by first investigating proteins related to immune system activation in depression and psychosis separately, and then identifying biological underpinnings of psychotic-like symptoms in depression.Specifically, we first assessed in major depressive disorder central nervous system levels of metabolites along the kynurenine pathway, a pathway that is regulated by the immune system and implicated in depressive and psychotic disorders (paper I). We found an imbalance between neuroprotective versus neurotoxic metabolites in blood and decreased levels of a neuroprotective metabolite in cerebrospinal fluid of patients with depression.Next, we assessed patterns of proteins implicated in immune-system function that distinguish first episode psychosis and healthy controls (paper II). Results indicate prominent changes in patients compared to controls, partially replicating previous findings and partially highlighting proteins that have not previously been assessed in psychosis.Lastly, we investigated psychotic-like symptoms in patients with major depressive disorder, finding a relation to immune system markers (paper III) and changes in connectivity between brain structures that integrate information about the physical body and autobiographic information into a sense of self (paper IV).In summary, the results from this thesis suggest that both in major depressive disorder and first episode psychosis there might be a dysregulation of the immune system and closely related systems such as the kynurenine pathway. These commonalities could further underlie the prevalence of subclinical psychotic-like symptoms in major depressive disorder. Ultimately, a better understanding of the underlying biological mechanisms of psychiatric disorders and, transdiagnostically, their symptoms will help formulate empiricallyinformed frameworks to guide clinical diagnostic processes and treatments.
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| 4. |
- Korhonen, Laura, Professor, 1974-, et al.
(författare)
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Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients
- 2023
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Ingår i: Translational Psychiatry. - : Springer. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
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