Comparing frequencies of adolescent suicide attempters pre- and during COVID-19 pandemic school terms.

BACKGROUND: The COVID-19 pandemic had and still have a major impact on adolescent mental health and consequently on suicidal behavior. However, few studies have investigated whether the pandemic has changed the patterns and the triggers of suicidality peaks in adolescents, e.g., seasonal patterns or family conflicts. We hypothesized that the pandemic modified suicidality rates: an increment of suicide attempts would be observed in the first semester of the academic year during COVID-19 pandemic compared to the same period of previous academic year; and the precipitating factors would be more related to social stressors during the pandemic school year. METHODS: A retrospective cross-sectional study was conducted to assess the precipitating factors, also including school-related factors and cognitive skills, of adolescent suicide attempters occurred in the first and second semesters of the year before the pandemic lockdown (study periods 1 and 2) and the year after (study periods 3 and 4). RESULTS: The sample consisted of 85 adolescents aged between 12 and 17 recruited consecutively from March 2019 to March 2021 at emergency ward because of suicide attempt. Forty-eight adolescents (55.3% of the sample) were attended before the lockdown (pre-pandemic group) and 38 (44.7%) the year after. The results showed a higher proportion of female suicide attempters in period 4 (Sept 2020-Feb 2021) respect to period 3 (Mar 2020-Aug 2020), i.e., pandemic semesters compared with the increment observed between period 2 and 1 (prepandemic semesters; Fisher's exact test = 4.73; p = 0.026). The multinomial regression models showed a significant effect in the frequency of adolescents who attempted suicide (ratio χ2 = 15.19, p = 0.019), accounted by the differences between period 4 (Sept 2020-Feb 2021) and period 1 (Mar 2019-Aug 2019), with depressive symptoms being a significant contributing factor (Exp(b) = 0.93; p = 0.04). Additionally, social triggers and age were found to be significant risk factors for suicide attempts in the first semester of the pandemic academic year (period 4) compared to the same semester of the pre-pandemic year (period 2; Exp(b) = 0.16, p = 0.01, and Exp(b) = 1.88, p = 0.006, respectively). CONCLUSIONS: During the pandemic, the decrement between first and second semester of the number of females attempting suicide was more pronounced than in the prepandemic school year -though this findings lacked statistical power due to very limited sample size-. Change in the frequency of adolescent attempting suicide in the different school periods was associated with greater severity of depressive symptoms. Social relations in back-to-school after the lockdown were also associated with the number of adolescents attempting suicide.

Depressive-Like Effects of Foreclosing: A Cross-Sectional Study of Hair Cortisol Concentration.

INTRODUCTION: Foreclosing and home eviction have been associated with various negative health outcomes, probably due to exposure to such stressful circumstance, but there is no evidence about foreclosure and home eviction to elicit cortisol responses. METHODS: Participants who recently had received a court eviction notice were compared to subjects suffering a depressive disorder and to healthy controls in terms of hair cortisol concentrations. RESULTS: Subjects under the stressful circumstance of foreclosure and patients with depression showed comparable concentrations in most of the hair segments while healthy subjects displayed the lowest levels of cortisol. CONCLUSION: The findings show that foreclosure and home eviction are associated with increased cumulative hair cortisol and with depressive-like symptoms. Foreclosing procedures yielded to maintain high levels of cortisol which may increase the risk to develop major depression.

Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study.

BACKGROUND: Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior. METHODS: We analyzed 7,860 magnetic resonance images of children 9-11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also obtained several behavioral data (cognition, behavioral problems, prodromal psychotic experiences, prosociality, impulsivity) to explore the potential mediatory role of brain volumes on behavior. RESULTS: In the 7,860 children analyzed (median age = 9 years and 11 months; 49.9% female), whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the left lateral orbitofrontal cortex proved to be very robust to the addition of potentially confounding covariates, random selection of siblings, and splitting the sample in two. The volume of the left pars orbitalis and the left lateral orbitofrontal cortex appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist. CONCLUSIONS: Our findings suggest that breastfeeding is a relevant factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal cortex regions. This, in turn, may impact impulsive personality and mental health in early puberty.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

Dealing with heterogeneity of cognitive dysfunction in acute depression: a clustering approach.

BACKGROUND: Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients. METHODS: In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping. RESULTS: Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%). CONCLUSIONS: The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses.

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial.

BACKGROUND: Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. METHODS: A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. DISCUSSION: To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. TRIAL REGISTRATION: Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

Absence of association between the level of lethality and the recidivism of suicide attempts in a Spanish province.

INTRODUCTION: Suicidal behaviour is a major health problem in Spain. The aim of this study is to examine the relationship between the recurrence of suicide attempts and the level of lethality reached, and the profile of repeaters who perform more lethal attempts. METHOD: All patients admitted for attempted suicide in a health area of 360,000 inhabitants from 2009 to 2014 (N=711) were systematically assessed. We compared clinical and demographic characteristics of these patients in terms of lethality (low versus moderate-severe) and recidivism (1-2 attempts versus >2 attempts) using univariate analyses and regression models. Later, we repeated the analyses after distributing the sample into four groups depending on the presence or absence of high lethality and/or recidivism. RESULTS: Recidivism was associated with the middle-age group (35-65 years), the lack of professional activity, and personality or substance use disorders. Lethality was associated with male gender, extreme age-groups, the use of a violent method, and affective disorders, but not with recidivism. Multiple suicide attempts and high lethality in a single patient was associated with 35-65 years age-group, male gender, violent methods, mental disorders, and inactivity. CONCLUSIONS: Different demographic and clinical factors indicate an increased risk of medical lethality and recurrence in suicidal patients. Our results show that at least some recidivist patients end up making more lethal and violent attempts with the passage of time, especially if they have psychiatric comorbidity.

Neuropsychological findings in recent onset schizophrenia and borderline personality disorder: a comparison study.

INTRODUCTION: Neurocognitive impairment is considered an essential symptom of schizophrenia, particularly in its early stages. Nonetheless, the neuropsychological features of borderline personality disorder (BPD) could cast doubt on the specificity of neurocognitive dysfunctions. The aim of this study is to determine whether neurocognitive deficits are specific to schizophrenia-spectrum conditions as compared to a similarly severe psychiatric illness like BPD. METHOD: A battery of neuropsychological tests was used to assess the abilities for attention, verbal memory and executive functions in a group of 34 borderline personality disorder (BPD) patients, 24 patients with first episode of a schizophrenia-spectrum disorder (FEP) and a group of 19 controls. RESULTS: ANOVA for multiple measures with subsequent post-hoc tests demonstrated significant effect sizes between controls and patients for all cognitive domains. However, the effect sizes of comparisons between both groups of patients were not significant. CONCLUSIONS: Results show significant neuropsychological impairment in both disorders when compared with normal controls, but no specific pattern of neurocognitive deficits for schizophrenia-spectrum disorders was found.

Lack of relationship between plasma levels of escitalopram and QTc-interval length.

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted ß = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R 2 = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test χ 2 = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.

NATURALISTIC COURSE OF MAJOR DEPRESSIVE DISORDER PREDICTED BY CLINICAL AND STRUCTURAL NEUROIMAGING DATA: A 5-YEAR FOLLOW-UP.

BACKGROUND: Despite its high recurrence rate, major depression disorder (MDD) still lacks neurobiological markers to optimize treatment selection. The aim of this study was to examine the prognostic potential of clinical and structural magnetic resonance imaging (sMRI) in the long-term MDD clinical outcomes (COs). METHODS: Forty-nine MDD patients were grouped into one of four different CO categories according to their trajectory: recovery, partial remission, remission recurrence, and chronic depression. Regression models including baseline demographic, clinical, and sMRI data were used for predicting patients' COs and symptom severity 5 years later. RESULTS: The model including only clinical data explained 32.4% of the variance in COs and 55% in HDRS, whereas the model combining clinical and sMRI data increased up to 52/68%, respectively. A bigger volume of right anterior cingulate gyrus was the variable that best predicted COs. CONCLUSIONS: The findings suggest that the addition of sMRI brain data to clinical information in depressive patients can significantly improve the prediction of their COs. The dorsal part of the right anterior cingulate gyrus may act as a potential biomarker of long-term clinical trajectories.

Efficacy of cognitive rehabilitation on psychosocial functioning in Borderline Personality Disorder: a randomized controlled trial.

BACKGROUND: Follow-up studies revealed that subjects with borderline personality disorder (BPD) present high rates of clinical remission, although psychosocial functioning often remains impaired. The aim of this study is to evaluate the efficacy of a cognitive rehabilitation intervention versus a psychoeducational program on psychosocial functioning in subjects with BPD. METHODS: A multicenter, randomized, and positive-controlled clinical trial was conducted. Seventy outpatients with BPD were randomized to cognitive rehabilitation or psychoeducational group interventions. Participants were evaluated after completion of the intervention period (16 weeks) and after the follow-up period (6 months). Psychosocial functioning, clinical and neuropsychological outcomes were evaluated. RESULTS: No main effects of group or group x time were observed on functionality but a significant effect of time was found. Post-hoc analyses showed that only cognitive rehabilitation increased psychosocial functioning significantly at endpoint. Psychoeducation showed a significant enhancement of depressive symptoms. CONCLUSIONS: Cognitive rehabilitation and psychoeducational interventions appeared to show good efficacy in improving disabilities in daily life in subjects with BPD. These interventions are easily implemented in mental health settings and have the advantage of improving general functioning and clinical symptoms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02033044. Registered 9 January 2014.

Effects of dialectical behaviour therapy-mindfulness training on emotional reactivity in borderline personality disorder: preliminary results.

UNLABELLED: Emotional dysregulation has been proposed as a hallmark of borderline personality disorder (BPD). Mindfulness techniques taught in dialectical behaviour therapy (DBT) appear to be effective in reducing affective symptoms and may enhance emotion regulation in BPD patients. In the present study, we assessed whether 10 weeks of DBT-mindfulness (DBT-M) training added to general psychiatric management (GPM) could improve emotion regulation in BPD patients. A total of 35 patients with BPD were included and sequentially assigned to GPM (n = 17) or GPM plus DBT-M (n = 18). Participants underwent a negative emotion induction procedure (presentation of standardized unpleasant images) both pre-intervention and post-intervention. Clinical evaluation was also performed before and after treatment. No differences were observed in emotional response at the post-treatment session. However, patients in the DBT-M group showed greater improvement in clinical symptoms. Formal mindfulness practice was positively correlated with clinical improvements and lower self-reported emotional reactivity. Our preliminary results suggest that mindfulness training reduces some psychiatric symptoms but may not have a clear effect on how patients respond to emotional stimuli in an experimental setting. KEY PRACTITIONER MESSAGE: No clear effect of mindfulness training was observed on emotional response to a negative emotion induction procedure. Application of the DBT-M module jointly to GPM induced better clinical outcomes than GPM alone. Formal mindfulness practice showed a positive impact on emotion regulation and clinical improvement.

Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder.

INTRODUCTION: Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. MATERIAL AND METHODS: This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl≥300µg/L) and low ones (Clz pl<300 µg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. RESULTS: There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07). The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). CONCLUSION: No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints.

Impact of Stress on Brain Morphology: Insights into Structural Biomarkers of Stress-related Disorders.

Exposure to acute and chronic stress has a broad range of structural effects on the brain. The brain areas commonly targeted in the stress response models include the hippocampus, the amygdala, and the prefrontal cortex. Studies in patients suffering from the so-called stress-related disorders -embracing post-traumatic stress, major depressive and anxiety disorders- have fairly replicated animal models of stress response -particularly the neuroendocrine and the inflammatory models- by finding alterations in different brain areas, even in the early neurodevelopment. Therefore, this narrative review aims to provide an overview of structural neuroimaging findings and to discuss how these studies have contributed to our knowledge of variability in response to stress and the ulterior development of stress-related disorders. There are a gross number of studies available but neuroimaging research of stress-related disorders as a single category is still in its infancy. Although the available studies point at particular brain circuitries involved in stress and emotion regulation, the pathophysiology of these abnormalities -involving genetics, epigenetics and molecular pathways-, their relation to intraindividual stress responses -including personality characteristics, self-perception of stress conditions…-, and their potential involvement as biomarkers in diagnosis, treatment prescription and prognosis are discussed.

Non-fatal suicide behaviours across phases in the COVID-19 pandemic: a population-based study in a Catalan cohort.

BACKGROUND: The COVID-19 pandemic has been extensively discussed in the context of its effect on mental health. Although global suicide rates have remained stable during the pandemic, the specific effect on non-fatal suicide behaviours during and after the pandemic remains underexplored. This study aims to investigate patterns of non-fatal suicide behaviours before, during, and after the pandemic. METHODS: In this cohort study, we used data from all hospitals in Catalonia, Spain, collected through the Catalan Suicide Risk Code, which is a specifically designed suicide attempt surveillance protocol, involving a face-to-face, in-depth psychiatric evaluation, after a Catalan resident presents any suicide risk behaviour in any public health-care setting. This evaluation centralises data from suicide registries across the territory. We included non-fatal suicide behaviours, meaning suicidal ideation or attempts that did not result in death, and excluded self-harm behaviours not judged to be linked with suicidal ideation. We considered three periods: the pre-confinement period (Jan 1, 2018, to the enforcement of the lockdown in Spain on March 14, 2020); the confinement period (March 14, 2020, to the end of lockdown on June 21, 2020); and the post-confinement period (June 21, 2020, to Dec 31, 2022). We used Bayesian structural time series models to assess the effect of pandemic phases on non-fatal suicide behaviours, and we ran stratified analyses by sex and age to identify distinct patterns among demographic cohorts. FINDINGS: We obtained 26 482 records from Jan 1, 2018, to Dec 31, 2022. The mean age was 37·94 years (SD 18·07), and the sample included 17 584 (66·4%) women and 8898 (33·6%) men. Data on ethnicity were not collected. Temporal trends showed a mild increase in non-fatal suicide behaviours from Jan 1, 2018, to March 13, 2020; a reduction during the confinement period; and a subsequent rise after confinement. Bayesian models suggested a significant causal effect of lockdown easing, resulting in a 50·77% increase in non-fatal suicide behaviours (95% credible interval [CrI] 26·62-76·58; p<0·0001). Stratified analyses indicated that the easing of lockdown resulted in a significant increase in non-fatal suicide behaviours among women (25·92%; 6·71-44·72; p=0·011) and among individuals aged 18 years and younger (72·75%; 38·81-108·11; p<0·0001). INTERPRETATION: This study provides a comprehensive examination of non-fatal suicide behaviours in Catalonia, Spain, emphasising the dynamics of different COVID-19 pandemic phases. The initial reduction during strict lockdown aligns with Joiner's Interpersonal Theory of Suicide, whereas the post-confinement rise reflects complex factors, including social isolation and economic challenges. Sex-specific and age-specific analyses underscore distinct vulnerabilities, emphasising the need for targeted preventive strategies. FUNDING: Centro de Investigación Biomédica en Red de Salud Mental annual budget of G21, Agència de Gestió d'Ajuts Universitaris i de Recerca of the Generalitat de Catalunya. TRANSLATIONS: For the Catalan and Spanish translations of the abstract see Supplementary Materials section.

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.

Hippocampal dysfunction in cured Cushing's syndrome patients, detected by (1) H-MR-spectroscopy.

BACKGROUND: Proton magnetic resonance spectroscopy ((1) H-MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushing's syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure. OBJECTIVE: To investigate metabolites in the hippocampi of CS patients and controls, using (1) H-MRS. PATIENTS AND METHODS: Eighteen right-handed cured CS patients (age 44·8 ± 12·5 years, 12·6 ± 3·8 years of education) and 18 right-handed healthy controls, matched for age (40·0 ± 11·9) and years of education (14·4 ± 3·8), underwent 3-Tesla magnetic resonance imaging (3T MRI) and (1) H-MRS including the head of each hippocampus. Concentrations of Glu (Glutamate), Glx (Glutamate + Glutamine), NAA (N-Acetyl-aspartate), total NAA (N-Acetyl-aspartate + N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes (mm(3) ) were additionally calculated using an automated procedure (FreeSurfer). RESULTS: CS patients had lower NAA than controls in the left and right hippocampus (5·2 ± 1·0 vs 6·1 ± 0·7, P < 0·05; 4·9 ± 0·8 vs 6·1 ± 0·6, P < 0·001, respectively), and lower total NAA on the right side (5·7 ± 0·9 vs 6·3 ± 0·9, P < 0·05), suggesting neuronal dysfunction/loss. CS patients had higher Glx than controls in both hippocampi (10·4 ± 1·9 vs 8·6 ± 1·4, P < 0·01; 9·9 ± 1·6 vs 8·9 ± 1·3, P < 0·05, respectively), suggesting glial proliferation, as a repair mechanism after neuronal dysfunction. No differences were found in the other brain metabolites, and there were no differences in left (3815·78 ± 502·96) and right (3980·75 ± 369·44) total hippocampal volumes between CS patients and controls (3945·08 ± 408·90 and 4108·39 ± 365·11, respectively). CONCLUSION: Persistently abnormal metabolites are evidenced in the hippocampi of CS patients despite endocrine cure. These functional alterations could be early markers of glucocorticoid neurotoxicity, preceding hippocampal volume reduction.

Effects of illness duration and treatment resistance on grey matter abnormalities in major depression.

BACKGROUND: Findings of brain structural changes in major depressive disorder are still inconsistent, partly because some crucial clinical variables have not been taken into account. AIMS: To investigate the effect of major depressive disorder on grey matter volumes. METHOD: Voxel-based morphometry was used to compare 66 patients with depression at different illness stages (22 each with first-episode, remitted-recurrent and treatment resistant/chronic depression) with 32 healthy controls. Brain volumes were correlated with clinical variables. RESULTS: Voxel-based morphometry showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus (P<0.05, family wise error-corrected). Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula. CONCLUSIONS: Frontotemporolimbic areas are smaller in the patients with severe depression and are associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting major depressive disorder on grey matter.