Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

The effect of emotional faces on reward-related probability learning in depressed patients.

BACKGROUND: Existing research indicates that individuals with Major Depressive Disorder (MDD) exhibit a bias toward salient negative stimuli. However, the impact of such biased stimuli on concurrent cognitive and affective processes in individuals with depression remains inadequately understood. This study aimed to investigate the effects of salient environmental stimuli, specifically emotional faces, on reward-associated processes in MDD. METHODS: Thirty-three patients with recurrent MDD and thirty-two healthy controls (HC) matched for age, sex, and education were included in the study. We used a reward-related associative learning (RRAL) task primed with emotional (happy, sad, neutral) faces to investigate the effect of salient stimuli on reward-related learning and decision-making in functional magnetic resonance imaging (fMRI). Participants were instructed to ignore emotional faces during the task. The fMRI data were analyzed using a full-factorial general linear model (GLM) in Statistical Parametric Mapping (SPM12). RESULTS: In depressed patients, cues primed with sad faces were associated with reduced amygdala activation. However, both HC and MDD group exhibited reduced ventral striatal activity while learning reward-related cues and receiving rewards. LIMITATIONS: The patients'medication usage was not standardized. CONCLUSIONS: This study underscores the functional alteration of the amygdala in response to cognitive tasks presented with negative emotionally salient stimuli in the environment of MDD patients. The observed alterations in amygdala activity suggest potential interconnected effects with other regions of the prefrontal cortex. Understanding the intricate neural connections and their disruptions in depression is crucial for unraveling the complex pathophysiology of the disorder.

Gradual Loss of Social Group Support during Competition Activates Anterior TPJ and Insula but Deactivates Default Mode Network.

Group forming behaviors are common in many species to overcome environmental challenges. In humans, bonding, trust, group norms, and a shared past increase consolidation of social groups. Being a part of a social group increases resilience to mental stress; conversely, its loss increases vulnerability to depression. However, our knowledge on how social group support affects brain functions is limited. This study observed that default mode network (DMN) activity reduced with the loss of social group support from real-life friends in a challenging social competition. The loss of support induced anterior temporoparietal activity followed by anterior insula and the dorsal attentional network activity. Being a part of a social group and having support provides an environment for high cognitive functioning of the DMN, while the loss of group support acts as a threat signal and activates the anterior temporoparietal junction (TPJ) and insula regions of salience and attentional networks for individual survival.

The effects of sexual abuse on female adolescent brain structures.

Objective: Sexual abuse (SA) is known for its effects on brain structures in adolescents. We aimed to explore if SA has any effect on limbic and prefrontal cortex (PFC) structures. We hypothesized that children with SA would have a thinner PFC with larger amygdala and hippocampus that lead to aberrations in threat detection, orientation and response circuit; that would be highly adaptive in a dangerous environment in the short term. Method: We included 57 SA and 33 healthy control (HC) female participants. In addition to psychiatric evaluation, we acquired 3 T MR images from all participants. We compared prefrontal cortical thicknesses, hippocampus and amygdala volumes between groups. Results: The age and education levels of study groups were matched, however, IQ scores and socioeconomic status (SES) scores of the SA group were lower than the controls. Total CTQ scores of the SA group were higher than the HC. Nevertheless, the mean value of sexual abuse scores was above the cut-off scores only for the SA participants. SA participants had larger right and left hippocampus and right amygdala volumes than the controls. SA group had reduced inferior frontal gyrus cortical thickness (T=3.5, p<0.01, cluster size=694 mm2, x=51 y=-30 z=6) than HC group. None of the structural findings were correlated with total or sexual abuse CTQ scores. Conclusion: Children with SA history has structural abnormalities in threat detection, orientation and response circuit. SA victims with no psychiatric diagnosis have a high probability of psychiatric problems with a possible contribution of these aberrations. SA cases that do not have a diagnosis must not be overlooked as they may have structural changes in emotion related brain regions. Careful follow-up is needed for all of all SA cases.

The Reflection of Self-Esteem on the Brain Structure: A Voxel Based Morphometry Study in Healthy Young Adults.

Introduction: Low self-esteem is a known risk factor for mental illnesses. Neuroimaging studies have identified evidence for a functional association between default mode network (DMN) and self-esteem levels. However, it is not clear whether there is a similar association between trait self-esteem and the structures composing DMN. This study aimed to investigate the relationship between the DMN associated brain structures and trait self-esteem. Methods: We obtained 3T structural magnetic resonance imaging (MRI) data of 75 healthy subjects and detected anatomical regions correlated with their Rosenberg Self-Esteem scores via voxel-based morphometry (VBM). Results: We found positive associations between self-esteem and regional grey matter volumes in the right temporoparietal junction/inferior parietal lobule (BA 39), cortical midline regions at precuneus/dorsal cingulate cortex (BA 31), rostral and dorsal anterior cingulate cortices (BA 32). Conclusion: The results of the current study support the fMRI studies suggesting self-esteem levels associated with DMN. Further neuroimaging studies should consider the functional and structural coupling of the default mode network during the execution of the functions related to self-esteem.

Personality change after 'flow diverter implantation' for intracranial aneurysm in a patient with stroke: A case report.

OBJECTIVE: This study aimed to present a patient with psychiatric symptoms that occur after flow diverter stent placement in a posterior communicating artery (PComA) aneurysm in a patient. DESIGN: A case study. METHOD: We performed cranial magnetic resonance imaging (MRI), magnetic resonance angiography, computed tomography angiography, neuropsychological tests, Levenson Self-Report Psychopathy Scale (LSRP), and a 25-item version of the Wender Utah Rating Scale (WURS-25). The patient's recent MRI was compared with previous MRIs. Neuropsychological testing consisted of a clinical interview, clinical assessment of frontal lobe syndrome, and tests evaluating the prefrontal cortex functions (Wisconsin Card Sorting Test-128 card version and Iowa Gambling Test). RESULTS: Our results showed that the patient's personality change and psychiatric symptoms occurred after the stent placement. Symptoms were still present at evaluation two and a half years after stent placement. CONCLUSION: The study demonstrates personality changes and psychiatric symptoms that might occur as complications following the placement of a flow diverter for incidentally detected aneurysm.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diverse Task Classification from Activation Patterns of Functional Neuro-Images Using Feature Fusion Module.

One of the emerging fields in functional magnetic resonance imaging (fMRI) is the decoding of different stimulations. The underlying idea is to reveal the hidden representative signal patterns of various fMRI tasks for achieving high task-classification performance. Unfortunately, when multiple tasks are processed, performance remains limited due to several challenges, which are rarely addressed since the majority of the state-of-the-art studies cover a single neuronal activity task. Accordingly, the first contribution of this study is the collection and release of a rigorously acquired dataset, which contains cognitive, behavioral, and affective fMRI tasks together with resting state. After a comprehensive analysis of the pitfalls of existing systems on this new dataset, we propose an automatic multitask classification (MTC) strategy using a feature fusion module (FFM). FFM aims to create a unique signature for each task by combining deep features with time-frequency representations. We show that FFM creates a feature space that is superior for representing task characteristics compared to their individual use. Finally, for MTC, we test a diverse set of deep-models and analyze their complementarity. Our results reveal higher classification accuracy compared to benchmarks. Both the dataset and the code are accessible to researchers for further developments.

Abnormal global signal topography of self modulates emotion dysregulation in major depressive disorder.

Major depressive disorder (MDD) is a complex mental disorder featured by an increased focus on the self and emotion dysregulation whose interaction remains unclear, though. At the same time, various studies observed abnormal representation of global fMRI brain activity in specifically those regions, e.g., cortical midline structure (CMS) in MDD that are associated with the self. Are the self and its impact on emotion regulation related to global brain activity unevenly represented in CMS relative to non-CMS? Addressing this yet open question is the main goal of our study. We here investigate post-acute treatment responder MDD and healthy controls in fMRI during an emotion task involving both attention and reappraisal of negative and neutral stimuli. We first demonstrate abnormal emotion regulation with increased negative emotion severity on the behavioral level. Next, focusing on a recently established three-layer topography of self, we show increased representation of global fMRI brain activity in specifically those regions mediating the mental (CMS) and exteroceptive (Right temporo-parietal junction and mPFC) self in post-acute MDD during the emotion task. Applying a complex statistical model, namely multinomial regression analyses, we show that increased global infra-slow neural activity in the regions of the mental and exteroceptive self modulates the behavioral measures of specifically negative emotion regulation (emotion attention and reappraisal/suppression). Together, we demonstrate increased representation of global brain activity in regions of the mental and exteroceptive self, including their modulation of negative emotion dysregulation in specifically the infra-slow frequency range (0.01 to 0.1 Hz) of post-acute MDD. These findings support the assumption that the global infra-slow neural basis of the increased self-focus in MDD may take on the role as basic disturbance in that it generates the abnormal regulation of negative emotions.

Structural and Functional Brain Alterations in Populations with Familial Risk for Depression: A Narrative Review.

LEARNING OBJECTIVES: After completing this activity, practitioners will be better able to:• Discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk• Define how structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. AIM: Familial history is associated with an increased risk for major depressive disorder (MDD). Despite the increased risk, some members of the familial high-risk population remain healthy, that is, resilient. Defining the structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. This study aimed to review the current literature and discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk. METHODS: A literature search on MRI studies investigating structural and functional alterations in populations at familial risk for MDD was performed using the PubMed and SCOPUS databases. The search was conducted through June 13, 2022. RESULTS: We reviewed and summarized the data of 72 articles (25 structural MRI, 35 functional MRI, 10 resting-state fMRI, one structural/functional MRI combined, and one structural/functional/resting-state fMRI combined). These findings suggested that resilience in high-risk individuals is related to the amygdala structure, frontal lobe activity, and functional connectivity between the amygdala and multiple frontal regions. CONCLUSION: Resilient and vulnerable individuals exhibit structural and functional differences in multiple frontal and limbic regions. However, further systematic longitudinal research incorporating environmental factors is required to validate the current findings.

Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium.

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

The role of educational attainment and brain morphology in major depressive disorder: Findings from the ENIGMA major depressive disorder consortium.

Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Emotional context effect on recognition of varying facial emotion expression intensities in depression.

BACKGROUND: Previous research has indicated that Major Depressive Disorder (MDD) patients have deficits in the process of facial emotion recognition. In most of these studies, isolated emotional faces were used, and the effect of the surrounding context of the face was neglected. We aimed to investigate how context emotion (sad or happy) affects facial emotion recognition and whether this effect is different in depressive individuals compared to the control group. METHODS: Happy, sad, neutral facial expressions with congruent and incongruent visual contexts were presented to 51 MDD patients and 42 matched healthy controls. Emotional facial expressions are presented as morphs gradually expressing happiness or sadness with 40% and 80% intensity levels. Mean reaction time, mean accuracy rate, and mean emotion intensity rating score was calculated for each condition. RESULTS: The performances on facial emotion intensity rating and accuracy rate were similar between MDD patients and controls. MDD patients were slower to recognize all facial emotions and to recognize facial emotions with emotionally incongruent backgrounds compared to congruent ones. LIMITATIONS: Antidepressant therapy of patients might have affected our results. CONCLUSIONS: Emotional contextual features have an important role in facial emotion recognition but this effect is independent of depression. Longer reaction time in depression may be related to some cognitive impairments.

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

A longitudinal study of lateral ventricle volumes in deficit and non-deficit schizophrenia.

Although it is generally accepted that negative symptoms of schizophrenia are associated with larger lateral ventricles, this general assumption could not be validated in patients with primary negative symptoms. To elucidate this issue, we conducted a five-year longitudinal study, including deficit (n = 13) and non-deficit (n = 26) schizophrenia patients with healthy controls (n = 18). Analysis with linear mixed effects modeling showed that both the left and the right lateral ventricles of the deficit patients enlarged more than the non-deficit patients. Our results suggest that structural alterations in deficit patients might follow a different trajectory than those in non-deficit patients.

Brain areas associated with resilience to depression in high-risk young women.

Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.

The Emerging Role of SPECT Functional Neuroimaging in Schizophrenia and Depression.

Over the last three decades, the brain's functional and structural imaging has become more prevalent in psychiatric research and clinical application. A substantial amount of psychiatric research is based on neuroimaging studies that aim to illuminate neural mechanisms underlying psychiatric disorders. Single-photon emission computed tomography (SPECT) is one of those developing brain imaging techniques among various neuroimaging technologies. Compared to PET, SPECT imaging is easy, less expensive, and practical for radioligand use. Current technologies increased the spatial accuracy of SPECT findings by combining the functional SPECT images with CT images. The radioligands bind to receptors such as 5-hydroxytryptamine 2A, and dopamine transporters can help us comprehend neural mechanisms of psychiatric disorders based on neurochemicals. This mini-review focuses on the SPECT-based neuroimaging approach to psychiatric disorders such as schizophrenia and major depressive disorder (MDD). Research-based SPECT findings of psychiatric disorders indicate that there are notable changes in biochemical components in certain disorders. Even though many studies support that SPECT can be used in psychiatric clinical practice, we still only use subjective diagnostic criteria such as the Diagnostic Statistical Manual of Mental Disorders (DSM-5). Glimpsing into the brain's biochemical world via SPECT in psychiatric disorders provides more information about the pathophysiology and future implication of neuroimaging techniques.

Bilateral keratoconus, acute hydrops and unilateral corneal perforation due to Tourette syndrome.

A 27-year-old male with a repetitive behavior of eyeball pressing for six months presented with decreasing visual acuity for three months. Upon arrival his best corrected visual acuity was 0.2 on the right and 0.6 on the left eyes. Scheimpflug camera system demonstrated grade 4 and grade 2 keratoconus, respectively. Psychiatric consultation revealed Tourette syndrome and treatment was started. Despite psychiatric treatment, acute hydrops occurred in both eyes decreasing visual acuity to hand motions bilaterally. Left corneal perforation due to ongoing habit of eyeball pressure was experienced which led the loss of light perception and phtisis bulbi. Although Tourette syndrome is rare, it might cause bilateral acute onset keratoconus when the repetitive movements affect periocular region. Psychiatric treatment should be considered as early as possible in these patients in order to prevent unfavorable complications.

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder.

BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.